Mechanics and Mathematical Modeling of Class III Treatment with Orthodontic Appliances with a Movable Ramp

Treatment of class III is a current problem in orthodontics that requires constant improvement of its methods, development of new or modifications of known methods and techniques. We have developed and studied the modification of removable functionally-directing orthodontic appliances for treatment of Class III, which consists of a plastic base, vestibular arc, retaining clasps, ramp, which is connected with the base by means of two torsion springs. Its usage ensures a prolonged contact of ramp with the teeth. We studied two types of club-shaped springs (torsion springs): one spring, which create an amortization effect during the action of the ramp, but do not change its inclination angle and second one – spring that seek to increase the angle of the ramp inclination due to the disclosure of its curl

The Method of Light Dose Measurement During Phodinamic Therapy

A new method of light dose monitoring during the photodynamic therapy of abdominal cavity organs was developed. To apply this method specially developed sensors were constructed. For these sensors the temporal and distance dependences of light doses were received and analyzed. It was shown that the light dose from the operating lamp is large enough in laser light field to be taken into account when planning photodynamic therapy. Keywords: PDT, light doses, other source of light in PDT, photodynamic therap

Порожниста сферична молекула діоксиду силіцію (SiO2)20(H2O)10: теоретичні розрахунки IЧ-спектру

The IR spectrum of hollow spherical molecule (SiO2)20(H2O)10 have been calculated within harmonic approximation using density functional theory method (exchange-correlation functional B3LYP and basis set 6-31G (d, p)) and an assignment have been made of the frequencies to the forms of vibrations. It has been shown that the theoretically calculated spectrum of molecule (SiO2)20(H2O)10 is consistent with the experimental spectra of nanospheres, so the molecule (SiO2)20(H2O)10 and its higher homologues can be used in quantum-chemical calculations of the properties of synthesized hollow nanospheres (d ≈ 290 nm).Методом функціоналу густини з гібридним обмінно-кореляційним функціоналом B3LYP і базисним набором 6-31G(d, p) в гармонічному наближенні розраховано інфрачервоний спектр порожнистої сферичної молекули (SiO2)20(H2O)10 та виконано віднесення частот у відповідністю з формою коливань. Показано, що теоретично розрахований спектр молекули (SiO2)20(H2O)10 узгоджується із експериментальним спектром наносфер, а тому молекулу (SiO2)20(H2O)10 та її вищі гомологи можна використовувати при квантовохімічних розрахунках властивостей синтезованих порожнистих наносфер (d ≈ 290 нм)

The Organisation of Educational Space in the New Ukrainian School

Objective: The paper covers the issue of organisation of educational space of primary education in the conditions of establishment of the NUS. The purpose of the study was to determine the specific features in the organisation of educational space in foreign educational institutions and to provide recommendations for the organisation of educational space of the NUS.Background: The school begins with the organisation of new educational space as a carrier of symbolic information, which ensures additional opportunities for the cognitive, aesthetic, ethical development of the subjects of the educational process. The ideas of organising the educational space of foreign countries, with a clear division into the physical environment, curriculum, human factors, are embodied in the practice of the New Ukrainian School (NUS) to organise opportunities to meet the needs of the educational process while having its own features.Method: The authors used communicative, cognitive, transformative, systematising and control methods of teaching during the research.Results: The concept of "educational space" is described; models of organisation of educational space are presented. The paper provides the analysis of an array of works of scholars, which cover various aspects of the definition of educational space. The educational sources, which are determined by the Methodical recommendations on the organisation of the educational space of the New Ukrainian School, are analysed.Conclusion: Recommendations are given to future primary school teachers on the organisation of educational space and educational sources in classrooms of modern primary school. The general conclusions concerning the investigated problem are formulated

IGHV3-21 gene expression in patients with b-cell chronic lymphocytic leukemia in Ukraine

The aim of the study was to evaluate the frequency of IGHV3-21 gene usage and its clinical significance for patients with B-cell chronic lymphocytic leukemia (CLL) in Ukraine. Patients and Methods: Immunoglobulin variable heavy chain (IGHV) gene repertoire was studied in 189 CLL patients using reverse transcribed polymerase chain reaction and direct sequence of amplified products. Results: IGHV3-21 gene expression was found in 11 cases (5.8%), and its frequency was intermediate between Scandinavian (11.7%) and Mediterranean CLL (2.9%) cohorts. The most of cases (9 of 11) belonged to subset with heterogeneous HCDR3 (heteroHCDR3 subset), and only 2 cases – to subset with classical short ARDANGMDV motif (homHCDR3 subset). Six IGHV3-21 cases were mutated and 5 cases were unmutated. All unmutated cases (all were from heteroHCDR3 subset) had similarity of their HCDR3s with previously published sequences. The differences in overall (OS), progression-free (PFS) and treatment-free survival (TFS) for IGHV3-21 positive patients in comparison with CLL patients expressing the other IGHV genes were statistically insignificant. These survival parameters were comparable also for CLL patients with mutated IGHV3-21 gene usage and expression the others mutated IGHV genes. But remarkable feature of IGHV3-21 expressing patients was high incidence of solid tumors. They have developed in 4 IGHV3-21 positive cases (36.4%) and in 10 cases with expression of the others IGHV genes (5.6%, p = 0.0002). Furthermore, in small group of 6 patients with mutated IGHV3-21 gene expression, 3 patients had solid tumors and one underwent Richter transformation. Unmutated IGHV3-21 gene expressed patients had worse OS and PFS in comparison with CLL patients that expressed the others unmutated IGHV genes. Conclusion: Presented data are in agrement with the opinion about negative prognostic significance of IGHV3-21 gene expression regardless its mutation status. IGHV3-21 expression was associated with development of secondary solid tumors. Revealed high level of homology in heteroHDR3s subset might suggest about possible antigenic influence also, in addition to homHCDR3 subset that was proposed earlier.Цель: оценить частоту использования гена IGHV3-21 и его клиническое значение для больных B-клеточным хроническим лимфолейкозом (ХЛЛ) в Украине. Больные и методы исследования: репертуар генов вариабельных участков тяжелых цепей иммуноглобулинов (IGHV) изучали у 189 больных с ХЛЛ с помощью полимеразной цепной реакции на базе обратной транскрипции и прямого сиквенса амплифицированных продуктов. Результаты: экспрессия гена IGHV3-21 выявлена у 11 пациентов (5,8%), что занимает промежуточное положение между Скандинавской (11,7%) и Средиземноморской (2,9%) когортами. Большинство случаев (9 из 11) относились к подгруппе с гетерогенным третьим комплементарнымрегионом (heteroHCDR3 подгуппа) и только 2 случая — к подгруппе с коротким классическим ARDANGMDV мотивом (homHCDR уппа). есть IGHV3-21-позитивных случаев были мутированными и 5 — немутированными. Все немутированные случаи (все из heteroHCDR уппы) имели сходство HCDR3 с анее описанными последовательностями. Различия в общей выживаемости (OS), длительности периода до прогрессии заболевания (PFS) и начала лечения (TFS) для IGHV3-21-позитивных больных были статистически незначимы по сравнению с пациентами с ХЛЛ с экспрессией других IGHV-генов. Указанные параметры также сравнивали между больными ХЛЛ с экспрессией мутированных IGHV3-21- и других IGHV-генов. Отличительной чертой пациентов с экспрессией IGHV3-гена была высокая встречаемость солидных опухолей. Они развились в 4 IGHV3-21-позитивных случаях (36,4%) и в 10 случаях с экспрессией других IGHV-генов (5,6%, p = 0,0002). Кроме того, в небольшой группе больных (6) с экспрессией мутированного IGHV3-21-гена у 3 возникли солидные опухоли и 1 пациента — синдром Рихтера. У больных с экспрессией немутированного IGHV3-21-гена определяли худшие показатели OS и PFS по савнению с пациентами с экспрессией других немутированных IGHV-генов. Выводы: представленные данные согласуются с мнением о самостоятельном негативном прогностическом значении для больных с ХЛЛ экспрессии IGHV3-21-гена вне зависимости от его мутационного статуса. IGHV3-21-экспрессия была ассоциирована с развитием вторичных солидных опухолей. Выявленный высокий уровень гомологии в heteroHDR3s-подгруппе может свидетельствовать о возможном антигенном влиянии в дополнение к антигенному влиянию в homHCDR уппе, что было установлено ране

p60-S6K1 represents a novel kinase active isoform with the mode of regulation distinct from p70/p85-S6K1 isoforms

The phosphatidylinositol-3-kinase (PI3K)/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway controls plenty of cellular functions regulating phosphorylation one of its mediators ribosomal protein S6 kinase 1 (S6K1). Alternative translation of the common S6K1 transcript can generate three protein kinase isoforms, including p85-S6K1, p70-S6K1 and p60-S6K1. The catalytic activity of S6K1 is modulated by mitogens and growth factors via phosphorylation at three critical sites such as the activation loop (T-loop site), turn motif (TM site), and hydrophobic motif (HM site). Both members of the PI3K/mTORC1 pathway, PDK1 and mTORC1, directly phosphorylate the T-loop site and HM site, respectively. Indeed, most studies­ aimed at elucidating S6K1 regulation have focused on p70- and p85-S6K1. Meanwhile, however, the activi­ty of p60-S6K1 and its regulation have not been elucidated so far. To test whether p60-S6K1 was an active kinase isoform that was regulated similar to p70/p85-S6K1, we employed previously generated p85–/p70–/p60+HEK-293 cells. First, an in vitro kinase assay confirmed the ability of p60-S6K1 to phosphorylate ribosomal protein S6 (rpS6), a well-known S6K1 substrate. Next, analysis of p60-S6K1 phosphorylation under different cell growth conditions showed that p60-S6K1 does not have detectable levels of phosphorylation at PDK1- and mTORC1-regulated sites, yet this isoform undergoes phosphorylation at the TM site. Finally, we found that activity of p60-S6K1 was not sensitive to mitogenic stimulation and cell treatment by potent inhibitor of the PI3K1/mTORC1-dependent signaling pathway rapamycin suggesting the existence of a PI3K/mTORC1-independent mechanism of p60-S6K1 regulation in HEK-293. The data of the current study suggest that the p60-S6K1 isoform possesses intrinsic kinase activity that is independent of PI3K/mTORC1 signaling regulation in HEK-293 cells. What is more, modulation of p60-S6K1 activity via the PI3K/mTORC1 signaling pathway seems to be cell-type specific, since the p60-S6K1 isoform undergoes PDK1- and mTORC1-mediated phosphorylation in breast cancer cell line MCF-7

ОПЫТ ПРИМЕНЕНИЯ ЭРИБУЛИНА В УСЛОВИЯХ РЕАЛЬНОЙ КЛИНИЧЕСКОЙ ПРАКТИКИ

Background: Eribulin mesylate was initially approved in 2010 by FDA as a third-line treatment for women with advanced breast cancer (ABC) pretreated with at least two lines of chemotherapy, and then in 2011 it was approved by EMA as a second-line therapy. Patients should have received an anthracycline and a taxane in either the adjuvant or metastatic setting. Since then, several studies have been conducted confirming its efficacy and safety. We report our experience of using eribulin in our centre in a real-life clinical setting.Materials and methods: 34 patients with ABC were enrolled to receive eribulin. From February 2016 to February 2017, patients were treated with standard doses of eribulin and evaluated for toxicity and responses. All of them had previously received anthracyclines and taxanes in either the adjuvant or metastatic setting. Median age was 60 years (range: 39–79). ECOG performance status was 1 or 2 at the time of enrollment. Median number of cycles of eribulin was 5 (range 2–10). Patients received eribulin from first-line chemotherapy to seventh-line chemotherapy for ABC. Median number of envolved visceral organs was 2 (range 1–4).Results: There were no complete responses. Partial responses were achieved in 26.4% (9/34), stabilization of the disease in 32.4% (11/34) and progression of the disease in 41.2% (14/34) of patients. The median progression-free survival was 4.09 months (range: 2.6–6.53). Main toxicities (grade 3–4) included peripheral neuropathy and neutropenia. Neuropathy was marked in 14.7% (5/34) and neutropenia in 14.7% (5/34) of patients. Dose reductions were required in 14.7% (5/34) of patients because of neutropenia.Conclusion: Our experience shows that eribulin has clinical activity as well as satisfactory tolerability in unselected patients in a reallife clinical setting. Thus, in our opinion, eribulin can represent a new option in treatment of ABC patients.Введение: Эрибулин впервые был зарегистрирован FDA в 2010 г. в качестве 3 линии терапии у пациентов с метастатическим раком молочной железы (мРМЖ), ранее получивших по крайней мере 2 линии химиотерапии по поводу распространенного процесса, включавшие антрациклины и таксаны. Далее в 2011 г. EMA одобрила эрибулин в качестве 2 линии химиотерапии. Пациенты должны были получать антрациклины и таксаны или в адъювантном, или лечебном режиме. К настоящему времени опубликован ряд исследований, подтверждающих эффективность и безопасность препарата. В настоящей работе представлен собственный опыт применения эрибулина в условиях реальной клинической практики.Пациенты и методы: С февраля 2016 по февраль 2017 г. лечение эрибулином получили 34 пациента с прогрессирующим мРМЖ с последующей оценкой эффективности и безопасности препарата. Все больные получили предшествующую терапию с использованием антрациклинов и таксанов по поводу местнораспространенного и/или метастатического рака. Средний возраст пациентов на момент включения в исследование составил 60 лет (от 39 до 79 лет). Статус общего состояния по шкале ECOG на момент включения был от 0 до 2. Медиана числа проведенных курсов химиотерапии эрибулином составила 5 (от 2 до 10 курсов). Пациенты получали эрибулин с первой по седьмую линии химиотерапии по поводу мРМЖ. Среднее количество пораженных органов – 2 (от 1 до 4 органов).Результаты: Полных регрессией отмечено не было. Частичная регрессия отмечена у 26,4% (9/34) пациентов, стабилизация болезни достигнута у 32,4% (11/34). Прогрессирование болезни зафиксировано у 41,2% (14/34) пациентов. Медиана выживаемости без прогрессирования на терапии эрибулином мРМЖ составила 4,09 (95% ДИ 2,6–6,53) месяца. Наиболее клинически значимой (3–4 степени) токсичностью стали нейтропения и полинейропатия. Нейтропения была отмечена у 14,7% (5/34), полинейропатия также у 14,7% (5/34) пациентов. 5 больным (14,7%) потребовалась редукция дозы эрибулина в связи с нейтропенией.Выводы: Проведенный нами анализ демонстрирует, что эрибулин является активным препаратом с предсказуемым и управляемым профилем безопасности при лечении пациентов с мРМЖ в условиях реальной клинической практики. Таким образом, по нашему мнению, эрибулин может стать новым вариантом лечения пациентов с мРМЖ

Deep awareness as a factor of environmental motivation at sea

There are environmental problems at sea and some of them are specific. The International Maritime Organization is on the way of strict controlling permanently intensification regulations. One of the most important of them is the International Convention for the Prevention of Pollution from Ships (MARPOL). To prevent uncontrolled and undesired actions of seafarers officers are interested in strong methods including motivating others and themselves as leadership skills are requested by practice and the International Convention on Standards of Training, Certification and Watchkeeping for Seafarers (STCW). After considering different types of motives, factors in/decreasing their effectiveness existing at sea, the authors developed the practical research, analyzed the revealed data on the nature of the dominating motives among cadets of the Maritime University and the seafarers, and concluded highly developed awareness of the existing pollution at sea. Established forming experiment proved that the deep awareness of environmental problems adds to the inside, the strongest environmental motivation to fallow International regulations, acceptable from both behavioral and self-controlling points of view. Further actualized professional self-organization strategy helped to educational ecological project development, which were involved in the working courses

Фотодинамическая терапия больной с впч–ассоциированной lsil шейки матки (клиническое наблюдение)

The article describes a clinical example of timely, safe and effective photodynamic therapy (PDT) in a patient diagnosed with human papillomavirus (HPV) CIN I-associated cervical cancer after ineffective vaccination with 4-valent Gardasil vaccine. Clinical case demonstrates the low effectiveness of HPV vaccination in patients with established HPV infection. In this patient, the lack of adequate treatment for about 1.5 years led to the development of HPV associated CIN I of the cervix. Center for Laser and Photodynamic Diagnostics and Therapy of Tumors and MRI P.A. Herzen, the patient underwent a course of antiviral PDT with the achievement of complete regression of dysplasia and complete eradication of HPV viruses. The patient tolerated the treatment well, without complications. The period of relapse-free follow-up is 19 months.В статье описывается клинический пример проведения своевременной, безопасной и эффективной фотодинамической терапии (ФДТ) у пациентки с диагнозом ассоциированной с вирусом папилломы человека (ВПЧ) СIN I шейки матки после неэффективной вакцинации 4-валентной вакциной гардасил. Клиническое наблюдение демонстрирует низкую эффективность вакцинации против ВПЧ больных с установленной ВПЧ инфекцией. У данной пациентки отсутствие адекватного лечения на протяжении около 1,5 лет привело к развитию ВПЧ ассоциированной CIN I шейки матки. В Центре лазерной и фотодинамической диагностики и терапии опухолей и МР МНИОИ им. П.А. Герцена пациентке проведен курс противовирусной ФДТ с достижением полной регрессии дисплазии и полной эрадикации вирусов ВПЧ. Лечение пациентка перенесла хорошо, без осложнений. Срок безрецидивного наблюдения – 19 мес