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Drug induced bradycardia is a frequent reason for hospitalization in cardiology clinic. Knowing the causes of this type of bradycardia is important for the proper management of these patients. Pyridostigmine bromide is an indirect parasympathomimetic drug, inhibitor of the cholinesterase enzyme. Pyridostigmine decrease the breakdown of acetylcholine, which is the natural neurotransmitter of the electrical impulses send by the somatic and parasympathetic nervous systems. Despite its relative safety and effectiveness, in rare cases there have been reports of conduction disturbances of the heart. In this clinical case report, we present a patient with atonic bladder treated with pyridostigmine. The patient developed a rare adverse reaction of the drug with an induced second-degree аtrioventricular block 2:1 type. The bradycardia caused pronounced symptoms which forced hospitalization in intensive cardiology clinic.

Abstract Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p

Атипичните демиелинизиращи лезии при пациенти с множествена склероза (МС) (тумороподобни демиелинизиращи лезии, лезии с кавитация на бялото мозъчно вещество, лезии, подобно на тези при левкодистрофия), макар и редки, създават сериозни диференциално-диагностични и терапевтични проблеми. Представени са 3 клинични случая на деца – едно с концентрична склероза на Balo и две с доказана диагноза МС, при кои то се наблюдават атипични магнитно-резонансни находки (МРТ) в хода на заболяването или при първоначалната клинична изя ва. Първият пациент е с остра изява на хемипареза и хемихипестезия при МРТ данни за окръглена тумороподобна перивентрикулна лезия вляво в бялото вещество със слоеста структура, без мас-ефект и без перифокален едем. Предвид образ ната находка е поставена диагнозата концентрична склероза на Balo. Вторият пациент е момиче с множествена склероза, при което в МРТ при втори пристъп на заболяването се визуализира тумороподобна лезия. Третият случай е на момче с тежко протичане на МС, с чести пристъпи и тежка инвалидизация в хода на проследяване, при което около 3 години след началото на заболяването се регистрират обширни, подобни на левкодистрофия лезии, съпроводени с кавитация на бялото мозъчно вещество. Развитието на магнитно-резонансната томография позволява ранна и правилна диагностика на атипичните образни находки при МС. Наличието и на други типични за МС лезии, както и данните за олигоклоналност са рискови фактори за последващи рецидиви. В случаите, при които са покрити диагностичните критерии за МС, се препоръчва започване на модифицираща хода на заболяването терапия.

Откриването на тумороподобна МС често води до диагностична несигурност, особено ако лезиите се появяват при пациен ти без известно към момента демиелинизиращо заболяване. Супратенториалната ТМС може да бъде отграничена от тумор по някои специфични образни характеристики: несъответствие между големината на лезията и мас-ефектът и; специфичен патерн на контрастиране – отворен пръстен насочен към сивото вещество. Голямо предизвикателство е разграничаването на ТМС от първичен ЦНС лимфом (PCNSL). Подозренията за мозъчен тумор често налагат биопсия, която също може да покаже подвеждаща патохистологична находка. При солитарна тумороподобна лезия в миелона диагностичните усилия са насочени към изключване на спинални интрамедуларни тумори. Представени са два клинични случая, суспектни за тумороподибна МС в главен и гръбначен мозък с обсъждане и предложения за диагностични подходи за прецизиране на диагнозата. Тумороподобната МС е необичайна и трудна за диагностициране форма на първична демиелинизация, поради което е изключително важно интегрирането на клиничните и лабораторни данни с резултатите от образните изследвания и нерядко проследяване на случаите във времето.

The sunflower has the potential to be a highly competitive crop owing to its diversity market and the valuable oil it produces. Nevertheless, the amount of sunflower seed oil – a key factor for the crushing industry – is affected by genotype and environment, which sometimes is difficult to predict. The paper analyzes the theoretical principles of sunflower growth in Ukraine, highlights the current trends in the sowing of this crop, the influence of climatic factors of the environment on the prospects of the oilseed sunflower yield. The results of the research are presented for 3 years (2014–2016), during the authors conducted a grain quality observatory at the regional level, taking into account the climatic conditions of sunflower growth in different natural zones of Ukraine (from 45° to 51° north latitude and from 22° to 37° east longitude). Additionally, the research includes the coefficient of significance of the deviation from long-term climatic indicators, which makes it possible to forecast sunflower yield in the future. The analyzed data was obtained from the commercial fields with a minimum area of 40 ​ha in all Ukrainian regions except Crimea peninsula, Donetsk and Luhansk regions. The results obtained in research show the great diversity of oil content index as per both latitude and longitude meaning. If we consider the entire country, this survey shows that the seed oil content can change dramatically from year to year: e.g. 47.5% in one year versus 45.7% in another year. Regionally, these changes have a completely different dynamic with a gradual decrease in seed oil content in the southern part of the country. The main goal of the research was to identify the best sunflower growing areas in Ukraine according to the oil content index.

Triply periodic minimal surfaces (TPMSs) are found in many natural objects including butterfly wings, sea urchins, and biological membranes. They simultaneously have zero mean curvature at every point and a crystallographic group symmetry. A metamaterial can be created from such periodic surfaces or used as a reinforcement of a composite material. While a TPMS as a mathematical object has been known since 1865, only novel additive manufacturing (AM) technology made it possible to fabricate cellular materials with complex TPMS shapes. Cellular TPMS-based metamaterials have remarkable properties related to wetting/liquid penetration, shock absorption, and the absence of stress concentrators. Recent studies showed that TPMSs are also found in natural crystals when electron surfaces are considered. Artificial crystal-inspired metamaterials mimic such crystals including zeolites and schwarzites. These metamaterials are used for shock, acoustic waves, and vibration absorption, and as structural materials, heat exchangers, and for other applications. The choice of the crystalline cell of a material, as well as its microstructure, plays a decisive role in its properties. The new area of crystal-inspired materials has many common features with traditional biomimetics with models being borrowed from nature and adjusted for engineering applications.

The paper discusses the importance of professional improvement in all aspects of human work and influence. Emphasis is given to employee education in the domain of culture, which includes libraries. Finally, project Transcribus is described, whose goal is digitalization of printed and hand-written material, simplifying their use and application.

Heat Shock Protein 90 (HSP90), a major molecular chaperone, plays a crucial role in cell function by folding and stabilizing proteins and maintaining proteostasis. This study aimed to elucidate the prognostic impact of HSP90 in cervical cancer. We analyzed HSP90 expression using immunohistochemistry in cervical cancer tissue microarrays from 250 patients. This study investigated correlations between HSP90 expression levels and key clinical outcomes, including overall survival (OS), progression-free survival (PFS), and FIGO classification. The statistical analyses employed included the Kruskal–Wallis-H test, log-rank (Mantel–Cox), and Cox regression. Our findings indicate that high nuclear HSP90 expression is associated with improved OS, while high cytoplasmic HSP90 expression correlates with better PFS and a lower FIGO classification in cervical squamous cell carcinoma patients. These results suggest that HSP90 could serve as a positive prognostic factor in patients diagnosed with cervical squamous cell carcinoma, underlining its potential as a biomarker for patient prognosis and as a target for therapeutic strategies.

The study aims to develop an information-computing complex for computer design of a centrifugal compressor with parallel calculation of stages and optimization of the geometric parameters of the impellers and the diffusers. The paper presents a universal methodology and computerized information system of the main geometry parameter determination and optimization of the centrifugal compressor impellers and vanned diffusers. Optimization of cross-sectional areas of the input and output channels of the impeller and diffuser blade channels is held using a gradient descent method by gas flowrate quadratic integral deviation criteria. The information-computing complex is built on the algorithm proposed by the authors and implemented as a computer program with a human-machine interface. Calculation data are written in the form of numerical arrays with the possibility of interpolating data and obtaining graphical dependencies.

IntroductionThe enzymes Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) und 3 (RIPK3) as well as the protein Mixed lineage kinase domain like pseudokinase (pMLKL) play a role in the signaling cascade of necroptosis. This is a form of programmed cell death which is caspase-independent. High-risk human papilloma virus infection can inhibit necroptosis. Thereby, a persistent infection and consequently the development of cervical cancer can be triggered. Aim of this study was the analysis of the expression of RIPK1, RIPK3 and pMLKL in cervical cancer tissue and the evaluation of its prognostic value on overall survival, progression-free survival and additional clinical parameters.MethodsThe expression of RIPK1, RIPK3, and pMLKL in cervical cancer tissue microarrays of n = 250 patients was analyzed immunohistochemically. Further, the effect of C2 ceramide on several cervical cancer cell lines (CaSki, HeLa, SiHa) was examined. C2 ceramide is a biologically active short-chain ceramide that induces necroptosis in human luteal granulosa cells.ResultsSignificantly longer overall survival and progression-free survival rates could be detected in cervical cancer patients expressing nuclear RIPK1 or RIPK3 alone or simultaneously (RIPK1 and RIPK3). Cell viability and proliferation was reduced through C2 ceramide stimulation of cervical cancer cells. Simultaneous stimulation of C2 ceramide and the pan-caspase inhibitor Z-VAD-fmk, or the RIPK1-inhibitor necrostatin-1, partly reversed the negative effect of C2 ceramide on cell viability. This observation could imply that caspase-dependent and -independent forms of cell death, including necroptosis, can occur. AnnexinV-FITC apoptosis staining induced a significant increase in apoptotic cells in CaSki and SiHa cells. The stimulation of CaSki cells with C2 ceramide led to a significant percentual increase in necrotic/intermediate (dying) cells after stimulation with C2 ceramide. In addition, after stimulation with C2 ceramide, CaSki and HeLa cells live cell imaging showed morphological changes which are common for necroptosis.DiscussionIn conclusion, RIPK1 and RIPK3 are independent positive predictors for overall survival and progression-free survival in cervical cancer patients. C2 ceramide can reduce cell viability and proliferation in cervical cancer cells by inducing most likely both apoptosis and necroptosis.

Background. Collaborative Strategic Reading (CSR) is an instructional method in which students work together in a cooperative framework, jointly construct a model of text and come to its potential meaning through discussions. Purpose. A quasi-experimental pretest-posttest non-equivalent control group research design was used to examine the effects of cooperative grouping within the framework of CSR, with the aim of determining whether cooperative grouping is effective in developing EFL students’ reading skills. Method. The response variables included the students’ scores on questions testing Vocabulary, Factual Information, Prose Summary, Sentence Simplification, Reference Question and Insert text, whereas the explanatory variable was group membership (+/- cooperative), measured across three testing times (the beginning, middle and the end of the experimental intervention). Results. The results indicate that the students exposed to CSR within cooperative groups significantly developed those reading skills which focus on the comprehension of global information – prose summary, insert text and reference question. A possible explanation is that, in order to answer these questions, readers must approach the text in a holistic manner and focus on its main ideas, which seems to be facilitated by discussions in heterogeneous teams and negotiations of meaning resulting from those discussions. Conclusion. The main pedagogical implication of the results concerns the need for introducing cooperative grouping as an alternative to a typical university-level foreign language classroom, allowing teachers to organize an effective, interactive context for reading academic texts in English.

In the study reported a total of 145 students pursuing the academic title of a BA in English language and literature were tested with the aim of establishing which explanatory variables have the independent power to explain the level of English language speaking anxiety. The instrument used in the study was taken from Yaikhong et al. (2012) and adapted for the purposes of the current investigation. The response variable in the study was the average level of anxiety measured by means of the questionnaire, whereas the explanatory variables included gender, the year of study, the number of presentations students gave during the course of their studies, the grade in language skills, the expected grade, the self-perceived proficiency and the perceived difficulty of the English language. The results reveal that gender, the expected grade and the self-perceived proficiency can account for the variation in the levels of anxiety among students. The paper ends with suggestions of interventions for helping students cope with the negative effects of anxiety on their speaking performance and learning experiences.

Research in computer-mediated communication has pointed to online disinhibition effect, i.e., a tendency to interact with less restraint when online than in face-to-face contacts. The current study explores the presence and level of disinhibition in online communication among university students and sets it in the context of synchronous online foreign language learning. To this end, 284 university students who took a course in English as part of their study programs participated in the research. A quantitative approach employing a survey design was adopted and the results were analyzed by means of descriptive and inferential statistical tests in SPSS 25. The findings show that the overall level of online disinhibition is rather low among the participants-the students self-report they feel inhibited when using the internet and communicating online. It also shows that male students tend to be more disinhibited in online communication than females. Two factors, the ability to immerse themselves in online learning surroundings and the use of headphones while attending lessons online are found to produce higher disinhibition levels. The findings imply that the affective domain deserves special attention in creating and conducting online language courses and that the digital environment requires a specific student-centered approach that is yet to be explored and defined.

An important direction in the development of additive technologies is associated with the addition of ceramic particles (oxide, carbide, boride, and nitride ceramics) to metal powders. The prediction of the physical and mechanical characteristics of SiC-particle-reinforced composite materials (PRCMs) in comparison with experimental results was studied. A near-α Ti-4.25Al-2V titanium-alloy-based composite reinforced by 1 vol.% of SiC ceramic particles was produced using laser direct energy deposition. A multiscale modeling approach at the micro and macro levels was applied. At the micro level, the toughness and strength characteristics for a temperature interval of T = 20–450 °C were predicted using a representative volume element of PRCM with the nearly real shape of SiC particles. At the macro level, the features of plastic deformation and fracture of the PRCM were predicted by numerical modeling using the commercial software Digimat Student Edition ver. 2022.4 and Ansys Student 2023 R2. The addition of SiC particles was found to improve the physical and mechanical properties in the whole temperature range. The results of the numerical modeling were consistent with the experimental data (the deviation did not exceed 10%). The proposed approach for predicting the physical and mechanical properties of Ti-4.25Al-2V/SiC can also be used for other PRCMs obtained by laser direct energy deposition.

Mиопатия на Bethlem и вродената мускулна дистрофия на Ullrich образуват спектър от колагенопатии, причинени от гене тични мутации, кодиращи някоя от трите субединици на колаген VI. Фенотипът на Bethlem е относително доброкачест вен и се характеризира с проксимална доминантна миопатия, келоиди, контрактури, дистална хиперекстензивност и фоликуларна хиперкератоза. Представяме 4-годишно момиче с генетично доказана миопатия тип Bethlem, дължаща се на мутация в COL6A3 ген, с автозомно-доминантно унаследяване. Клиничната картина се представя от миопатен синдром със слабост на тазобедрената мускулатура, контрактури на Ахиловите сухожилия, мускулна хипотония. ЕМГ изследването показва характерни белези за миогенна увреда, a креатин киназата е с леко завишени стойности.

Малформациите на коровото развитие представляват макро- и/или микроскопски аномалии на мозъчната кора, които възникват в резултат на нарушение на нормалните етапи на кортикогенезата. Полимикрогирията (ПМГ) се характеризира с прекомерно голям брой, необичайно малки мозъчни гънки, плитки бразди, придаващи неправилна „камъчеста” повърхност на кората и „набраздена” граница на сиво-бялото вещество. Все повече доказателства сочат, че ПМГ настъпва вследствие на нарушена късна невронална миграция. Полимикрогирията е една от най-честите малформации на коровото развитие, свързана с различни клинични прояви, включващи епилепсия, когнитивен дефицит, двигателна дисфункция и говорни нарушения. Етиологията на ПМГ е хетерогенна и включва както генетични, така и негенетични причини. Към днешна дата повече от 50 гена са свързани с ПМГ. МРТ е изследването на избор за оценка детайлите при ПМГ и свързаните структурни аномалии. Важно е да се използват оптимални техники за изобразяване, включително тънки срези и специфични за възрастта протоколи. Генетичното консултиране е от полза за засегнатите деца и техните семейства. Стремежът е да се увеличи успехът при диагностициране на ПМГ, като по този начин се подобрят грижите и лечението на пациен тите.

The establishment of cultural societies and institutions throughout Serbia after the Balkan wars were one of the priorities of the Kingdom of Serbia. In addition to the Cultural League, there were also Serbian agricultural cooperatives, workers’ and party associations, united in an important mission – education, enlightenment and cultural uplifting of their people. The authors of the paper try to follow the historical development of the Cultural League, whose development and activities have created the conditions for the emergence of public libraries in Serbia.

In the present work, three versions of implementation of non-invasive bronchial asthma diagnostic system based on the author’s technique of noninvasive diagnosis of bronchopulmonary diseases are considered. The offered variants of diagnostic system can be used both in medical institutions and at patient’s home for the control of the patient’s condition with the purpose of monitoring the dynamics of the disease during treatment, as well as for preventive purposes. Three variants of implementation of the diagnostic system with various complexity are considered. The results of a radiofrequency scanning of a human chest phantom with included heterogeneity simulating the presence of sputum in the human chest is a consequence of bronchial asthma.