Cytotoxic Activity of Silyl- and Germyl-Substituted 4,4-Dioxo-3a,6a-Dihydrothieno[2,3−d]isoxazolines-2

The [2+3] dipolar cycloaddition of nitrile oxides to the double C = C bonds of thiophene-1, 1-dioxides leads to formation of the fused isoxazolines-2 (1, 2). Tumor growth inhibition of these compounds strongly depends on the nature of group IV A element increasing from slightly active tert-butyl derivatives to silicon and germanium containing analogues. The products of benzonitrile oxide cycloaddition have greater cytotoxic effect than the compounds obtained from the cycloaddition reaction of 2, 5-disubstituted thiophene-1, 1-dioxides with acetonitrile oxide. Fused silyl substituted isoxazolines-2 are stronger NO-inducers than their germyl and tert-butyl analogues

Professional Orientation of Learning of Medical Informatics for Future Dentists During the Studying of Expert Systems

Формулювання проблеми. Відсутність на кафедрах медичної інформатики повного комплексу прикладного програмного забезпечення для вивчення навчальної дисципліни «Медична інформатика» для різних спеціальностей, зокрема відсутність стоматологічних експертних систем та відповідної інформації щодо стоматологічних баз даних у навчальній літературі, щонайменше знижує навчальну мотивацію студентів-стоматологів щодо окремих тем або всієї дисципліни. Необхідність зміни ситуації спонукає викладачів до дій, зокрема до розробки додаткових професійно-орієнтованих завдань для майбутніх стоматологів. Матеріали і методи. При розробці практичних завдань застосовано аналіз, синтез, індукцію, дедукцію, порівняння, узагальнення. Зокрема, проведено аналіз літератури зі стоматологічних експертних систем, здійснено синтез і узагальнення знань з інформатики, стоматології і педагогіки для виділення основних властивостей експертної системи з метою збільшення доступності теоретичного й практичного матеріалу для студентів. Результати. У статті висвітлено досвід викладання теми з медичних експертних систем для студентів стоматологічного факультету на заняттях з медичної інформатики на кафедрі біофізики, інформатики та медичної апаратури Вінницького національного медичного університету імені М. І. Пирогова. Представлено практичні завдання в програмах MS Excel та MS Access і обґрунтовано причини вибору цих програм. Крім того, розглянуто приклади практичних завдань для студентів з високим початковим рівнем знань, умінь, навичок з інформатики. За основу завдань взято експертну систему з диференціальної діагностики форм пульпітів, яку розроблено авторами. Розроблена експертна система виступає демонстраційним прикладом на початку заняття та основою для розробки майбутніми стоматологами власної експертної системи впродовж заняття. За допомогою бази знань продукційної експертної системи студенти створюють продукційні правила з дев'яти стоматологічних захворювань одного типу (пульпіти) та використовують їх у процесі роботи в програмах MS Excel та MS Access. При виборі студентами комп'ютерної програми, відмінної від запропонованих, відводиться більше часу на виконання завдань та нараховуються додаткові бали за індивідуальну самостійну роботу. Висновки. Використання професійно-орієнтованих завдань на кожному практичному занятті активізує діяльність студентів, підвищує їхню зацікавленість до використання інформаційних технологій, збільшує мотивацію вивчення медичної інформатики, що, в свою чергу, сприяє кращому формуванню інформаційно-комунікаційної компетентності майбутніх лікарів-стоматологів.Formulation of the problem. Absence on the department of medical informatics the full complex of applied software for studying the educational discipline "Medical Informatics" for different specialties reduces the motivation of dental students to study separate topics or the whole discipline. Necessity of changing the situation induces teachers to take actions, in particular to develop additional professional- oriented tasks for future dentists. Materials and methods. Analysis, synthesis, induction, deduction, comparison, generalization were applied during the development of practical tasks. In particular, the literature from dental expert systems have been analyzed, the synthesis and generalization of knowledge on computer science, dentistry and pedagogy for the identification of the basic properties of the expert system was made in order to increase the accessibility of theoretical and practical material for students. Results. The article describes the experience of teaching topic from medical expert systems for students of the faculty of dentistry during the classes on medical informatics at the department of biophysics, informatics and medical equipment of National Pirogov Memorial Medical University (Vinnytsa). The practical tasks in MS Excel and MS Access programs are presented and the reasons for the choice of these programs are substantiated. In addition, examples of practical tasks for students with a high initial level of computer knowledge and skills are considered. The expert system developed by authors on differential diagnostics of forms of pulpitis is a basis of practical tasks as is a demonstration example at the beginning of the lesson and the basis for the development of their own expert system by future dentists during the class. Conclusions. Use professional-oriented tasks at every lesson activates the students, increases their interest in the use of information technology, increases the motivation of the study of medical informatics and, in addition, contributes to the better formation of information and communication competence of future dentists

Analysis of mutations in CDC27, CTBP2, HYDIN and KMT5A genes in carotid paragangliomas

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from paraganglionic tissue of the carotid body localizing at the bifurcation of carotid artery. These tumors are slowly growing, but occasionally they become aggressive and metastatic. Surgical treatment remains high-risk and extremely challenging; radiation and chemotherapy are poorly effective. The study of molecular pathogenesis of CPGLs will allow developing novel therapeutic approaches and revealing biomarkers. Previously, we performed the exome sequencing of 52 CPGLs and estimated mutational load (ML). Paired histologically normal tissues or blood were unavailable, so potentially germline mutations were excluded from the analysis with strong filtering conditions using 1000 Genomes Project and ExAC databases. In this work, ten genes (ZNF717, CDC27, FRG2C, FAM104B, CTBP2, HLA-DRB1, HYDIN, KMT5A, MUC3A, and PRSS3) characterized by the highest level of mutational load were analyzed. Using several prediction algorithms (SIFT, PolyPhen-2, MutationTaster, and LRT), potentially pathogenic mutations were identified in four genes (CDC27, CTBP2, HYDIN, and KMT5A). Many of these mutations occurred in the majority of cases, and their mutation type was checked using exome sequencing data of blood prepared with the same exome enrichment kit that was used for preparation of exome libraries from CPGLs. The majority of the mutations were germline that can apparently be associated with annotation errors in 1000 Genomes Pro ject and ExAC. However, part of the mutations identified in CDC27, CTBP2, HYDIN, and KMT5A remain potentially pathogenic, and there is a large body of data on the involvement of these genes in the formation and progression of other tumors. This allows considering CDC27, CTBP2, HYDIN, and KMT5A genes as potentially associated with CPGL pathogenesis and requires taking them into account in further investigations. Thus, there is a necessity to improve the methods for identification of cancer-asso ciated genes as well as pathogenic mutations

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

Oligothiophene-S,S-dioxides: A new class of thiophene-based materials

We report here that bissilylated oligothiophenes may be selectively oxidized at the thienyl sulfurs by m-chloroperbenzoic acid (m-CPBA) to afford stable S,S-dioxides having alternate aromatic and nonaromatic moieties. These compounds are characterized by enhanced electron delocalization, smaller optical gap, and greater electron affinity than the “fully aromatic” precursors

From easily oxidized to easily reduced thiophene-based materials

We report here a new strategy towards functionalization of oligothiophenes that consists of the chemical transformation of thienyl sulfurs into the corresponding S,S-dioxides. We show that this kind of functionalization, which implies the dearomatization of the thiophene rings, leads to very stable oligomers with increased electron delocalization and has also a dramatic effect on their electron affinity as deduced from their electrochemical reduction potential. It is worth mentioning that the synthesis and the characterization of unsubstituted thiophene S,S-dioxide has been reported only very recently and that only S,S-dioxides derived from polysubstituted thiophene are stable at room temperature. So far, no electrochemical data on this kind of compound have yet been published

Oligothiophene S,S-dioxides: Towards n-type semiconductor oligothiophenes?

A new class of thiophene based materials - oligothiophene S,S-dioxides, characterized by a much greater electron affinity than the precursor oligothiophenes - is described. © 1998 Elsevier Science B.V