Studying of immunophysiological properties of Yersinia Pestis strains with various plasmid composition

Data of Yersinia pestis plasmid structure influence on its adhesive properties and phagocytic activity of peritoneal macrophages in vitro are represented. It is shown that Y. pestis strains of diverse subspecies differing by a plasmid profile, particularly by one of the plasmids (pYP, pYV) lacking, possess low adhesive activity and promote the increase of laboratory animal phagocyte absorbing capacity

Fano resonances in plasmonic core-shell particles and the Purcell effect

Despite a long history, light scattering by particles with size comparable with the light wavelength still unveils surprising optical phenomena, and many of them are related to the Fano effect. Originally described in the context of atomic physics, the Fano resonance in light scattering arises from the interference between a narrow subradiant mode and a spectrally broad radiation line. Here, we present an overview of Fano resonances in coated spherical scatterers within the framework of the Lorenz-Mie theory. We briefly introduce the concept of conventional and unconventional Fano resonances in light scattering. These resonances are associated with the interference between electromagnetic modes excited in the particle with different or the same multipole moment, respectively. In addition, we investigate the modification of the spontaneous-emission rate of an optical emitter at the presence of a plasmonic nanoshell. This modification of decay rate due to electromagnetic environment is referred to as the Purcell effect. We analytically show that the Purcell factor related to a dipole emitter oriented orthogonal or tangential to the spherical surface can exhibit Fano or Lorentzian line shapes in the near field, respectively.Comment: 28 pages, 10 figures; invited book chapter to appear in "Fano Resonances in Optics and Microwaves: Physics and Application", Springer Series in Optical Sciences (2018), edited by E. O. Kamenetskii, A. Sadreev, and A. Miroshnichenk

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation

ТЯЖЕЛАЯ СОЧЕТАННАЯ ЧЕРЕПНО-МОЗГОВАЯ ТРАВМА: ОСОБЕННОСТИ КЛИНИЧЕСКОГО ТЕЧЕНИЯ И ИСХОДЫ

Severe multisystem craniocerebral injury (smcci) is characterized by long-term disability and high lethal rates. Objective: analysis of smcci, features of its clinical course and lethality, including the main causes and terms of death. Materials and methods. An analysis of 170 case histories of the deceased with smcci was carried out: 130 men (76.5%) and 40 women (23.5%). The average age is 43.3±17.5 years. Victims were divided into groups, depending on the combination of head trauma with injuries to other anatomical areas of the body. The analysis of lethality, including the main causes and terms of lethal outcomes, was conducted. Depending on the main causes of death, all the deceased were divided into five groups: massive blood loss and shock, edema and dislocation of the brain, infectious pulmonary complications, purulent intoxication and others. Depending on the terms of death, the victims were divided into four subgroups: i — up to 24 hours, ii — from 1 to 3 days, iii — from 3 to 10 days, and iv — more than 10 days. The severity of the damage was assessed according to the injury severity score (iss), the level of consciousness was assessed according to the glasgow coma scale (gcs). The frequency of development of infectious complications and its relation to the terms of death was analyzed as well. Results. In the distribution of the victims, depending on the main causes of death, it was found that: in 41.2% (70) cases, the main cause of death was edema and dislocation of the brain; 25.3% (43) — massive blood loss and shock; 15.9% (27) had purulent intoxication, 12.9% (22) had infectious pulmonary complications and 4.7% (8) died due to other causes. The number of patients who died on the first day was 62 (36.5%), while 35 victims (56.5%) died within the first 3 hours after admission. On the third day, 24 patients (14.1%) died, 37 patients (21.8%) died 3-10 days after admission, and 47 patients (27.6%) died later than 10 days after admission. There was a significant correlation between the severity of the trauma and the terms of death: spearman’s rank correlation coefficient = -0.637 (-0.718; -0.538), p<0.0001. A significant connection between the iss and the timing of death was indicated by the chi-square=99.495, degrees of freedom=9, p<0.0001 for the contingency table 4x4. A significant correlation between the development of the ipc and the terms of death was indicated by the analysis of the contingency table (2x4): chi-square=143.136 with degrees of freedom=3 and p<0.0001. Conclusion. In the general structure of smcci, victims with a combination of head and musculoskeletal injuries prevailed, the combination with a chest trauma was second, the combination with a trauma to the abdomen was third and the combination with a spinal injury was fourth. The main causes of death were edema and dislocation of the brain, massive hemorrhage and shock, infectious pulmonary complications, septic complications and others. The statistically significant relation was found between the trauma severity, the development of infectious complications, “main causes” on the one hand, and the terms of death on the other.Резюме. Тяжелая сочетанная черепно-мозговая травма (ТСЧМТ) характеризуется длительной утратой трудоспособности и высокой летальностью.Цель. Анализ ТСЧМТ, особенностей ее клинического течения и летальности, включая основные причины и сроки смертельных исходов.Материал и методы. Проведен анализ 170 историй болезни умерших с ТСЧМТ: 130 мужчин (76,5%) и 40 женщин (23,5%). Средний возраст пострадавших составил 43,3±17,5 года. Пострадавшие распределены по группам в зависимости от сочетания травмы головы с повреждениями других анатомических областей тела. Проведен анализ летальности, включая основные причины и сроки смертельных исходов. В зависимости от основных причин смерти все умершие были распределены на пять групп: массивная кровопотеря и шок, отек и дислокация головного мозга, инфекционные легочные осложнения (ИЛО), гнойная интоксикация и прочие. В зависимости от сроков смерти пострадавшие распределены на четыре подгруппы: I — до 24 ч, II — от 1 до 3 сут, III — от 3 до 10 сут и IV — свыше 10 сут. Оценка тяжести повреждений проводилась по Injury Severity Score (ISS), уровня сознания — по шкале комы Глазго. Анализировалась частота развития инфекционных осложнений и их связь со сроками смерти.Результаты. При распределении пострадавших в зависимости от основных причин смерти было выявлено, что у 41,2% (70 пациентов) основной причиной смерти явились отек и дислокация головного мозга, у 25,3% (43) — массивная кровопотеря и шок, у 15,9% (27) — гнойная интоксикация, у 12,9% (22) — ИЛО и у 4,7% пострадавших (8) смерть наступила от прочих причин. Число умерших в первые сутки составило 62 человека (36,5%), при этом 35 (56,5%) из них погибли в первые 3 ч от момента поступления. В 1-е–3-и сут погибли 24 пациента (14,1%), в срок от 3 до 10 сут — 37 (21,8%) и в срок свыше 10 сут — 47 пациентов (27,6%). Отмечается статистически значимая корреляция между тяжестью травмы и сроками смерти: коэффициент ранговой корреляции Спирмена составил -0,637 (-0,718; -0,538), р<0,0001. О статистически значимой связи между тяжестью повреждений по ISS и сроками смерти свидетельствует также тест Хи-квадрат, равный 99,495, количество степеней свободы 9, р<0,0001 для таблицы сопряженности 4х4. О статистически значимой зависимости между развитием ИЛО и сроками смерти свидетельствует анализ таблицы сопряженности 2х4: Хи-квадрат составил 143,136 при количестве степеней свободы 3 и р<0,0001.Заключение. Основными причинами смерти при ТСЧМТ явились: отек и дислокация головного мозга; массивная кровопотеря и шок; гнойно-септические осложнения; ИЛО и прочие. Выявлена статистически значимая связь между тяжестью травмы, развитием инфекционных осложнений, основными причинами смерти, с одной стороны, и сроками смертельных исходов с другой

Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

Background: Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Methods: Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.Results: RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. Conclusion: These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma. © 2010 Sadikovic et al; licensee BioMed Central Ltd

Eribulin-trastuzumab combination in HER2-positive metastatic breast cancer: updated results from a Russian observational study

Introduction. The standard of 1st line treatment of HER2+ metastatic breast cancer (mBC) is double blockade with trastuzumab and pertuzumab + taxane, 2nd line – Trastuzumab-emtazine. There are no standards for further treatment, as well as the optimal drug sequence. Expansion of the arsenal of therapeutic possibilities and the use of new combinations will certainly improve the results of treatment of this category of patients and increase their life expectancy.Aim. We sought to describe treatment patterns of  eribulin  and clinical outcomes of  metastatic HER2-positive breast cancer treated with eribulin  plus trastuzumab combination in  academic institutions and community oncology practices across the Russian Federation.Materials and methods. Patients treated with eribulin anytime between Jan, 2014 and Sep, 2019 with a diagnosis of MBC were identified by 23 providers from Russia. Providers retrospectively reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient.Results. 100 HER2-positive pts received eribulin in combination with trastuzumab. Median age was 55 (31–80) yrs and ECOG status 0–3. 67% pts had visceral metastases. Eribulin was administered as 1st and 2nd line to 23 (23%) pts, 3rd line to 31 (31%) pts, 4th line and later to 46 (46%). Median number of cycles was 5 (2–27). ORR was 12%, SD – 72%, SD > 6 months – 23%, PD – 16%. Clinical efficacy rate achieved in 35%. Median PFS was 5.07 months (95% CI 4.021–6.119). According to the ER-status the response to eribulin and trastuzumab was different. ORR was 18.8%, SD 72.9% in pts with ER-positive MBC (n = 48) and 5.8% and 71.2% respectively in ER-negative MBC (n = 52). Median PFS was 6.97 months (95% CI 3.924–10.016) in pts with ER-positive MBC and 4.67 months (95% CI 3.841–5.499) in ER-negative MBC (р = 0.3). The combination was well tolerated: dose reductions were required in 12% pts, withdrawal due to toxicity in 4% pts. The most common type of toxicity was hematological with neutropenia Gr III-IV in 14 (14%) pts. Peripheral neuropathy Gr III was observed in 5 (5%) pts. No cardiotoxicity was detected.Conclusions. This is the real-life data of clinical outcomes for patients receiving eribulin plus trastuzumab for HER2-positive MBC throughout the Russian Federation. Our experience with eribulin plus trastuzumab demonstrates that this combination may be a potential effective treatment option for HER-2 positive MBC patients

Real-space collapse of a polariton condensate

Microcavity polaritons are two-dimensional bosonic fluids with strong nonlinearities, composed of coupled photonic and electronic excitations. In their condensed form, they display quantum hydrodynamic features similar to atomic Bose–Einstein condensates, such as long-range coherence, superfluidity and quantized vorticity. Here we report the unique phenomenology that is observed when a pulse of light impacts the polariton vacuum: the fluid which is suddenly created does not splash but instead coheres into a very bright spot. The real-space collapse into a sharp peak is at odd with the repulsive interactions of polaritons and their positive mass, suggesting that an unconventional mechanism is at play. Our modelling devises a possible explanation in the self-trapping due to a local heating of the crystal lattice, that can be described as a collective polaron formed by a polariton condensate. These observations hint at the polariton fluid dynamics in conditions of extreme intensities and ultrafast times

Продолжительность жизни больных метастатическим почечно-клеточным раком в Российской Федерации: результаты многоцентрового регистрового исследования RENSUR3

Background. Overall survival (OS) data obtained in patients with metastatic renal cell carcinoma (mRCC) in real-world settings are rarely published. The objective of the RENSUR3 registry study was to collect information on the use of various therapeutic options for mRCC in real-world clinical practice and assess OS in a Russian population.Methods. Patients were retrospectively identified at 8 cancer centres in different Russian regions and enrolled in the study if the diagnosis of mRCC had been made in the period from January 2015 to December 2016. Anonymous data were collected online, the registry contained demographic characteristics and treatment and outcome data.Results. The study had 573 subjects included in the analysis. The average age of patients at mRCC diagnosis was 63.1 years; 14.5 % of them were aged > 75 years. 65.6 % of the subjects were men; 72% had received surgical treatment for the primary tumour; clear cell and non-clear cell carcinomas were detected in 84 % and 16 % of the patients, respectively.Drug therapy was used in 307 patients (54%). The median duration of any line of therapy was 10 months (95% CI 7.6-12.4). The most frequent treatment option was interferon (administered 161 times as part of any line of therapy or at different stages of treatment). Targeted therapy was given to 160 patients (52.1%), 112 of whom received it as first-line therapy. 87 subjects (28.3%) received > 2 lines of therapy. The 3-year OS rate was 21%, and the median OS was 12 months (95% CI 11.1-12.9). The median OS in the therapy and no therapy groups was 15.1 months and 6.9 months, respectively (Р<0.0001). The median life expectancy in patients receiving second-line therapy (median 18.4 months) was significantly higher than in patients treated with first-line therapy only (10.9 months, Р<0.001).Conclusions: The OS results of the RENSUR3 study are unsatisfactory, which apparently can be explained by the fact that drug therapy was used in only half the patients, the infrequent use of targeted drugs, and the rare administration of targeted therapy for second and subsequent lines of therapy in patients with progressive disease. Introduction of the latest drug therapy options, including checkpoint inhibitors, will help improve patients» life expectancy.Введение. Данные по общей выживаемости (ОВ) пациентов с метастатическим почечно-клеточным раком (мПКР) в реальной жизни публикуются редко. Задача регистрового исследования RENSUR3 заключалась в сборе сведений по применению разных вариантов терапии при мПКР в условиях реальной клинической практики и оценке ОВ в популяции российских пациентов.Методы. Пациентов ретроспективно идентифицировали в 8 онкологических центрах в разных регионах России и включали в исследование, если диагноз мПКР был установлен в период с января 2015 г. по декабрь 2016 г. Анонимные сведения собирали онлайн, регистр охватывал демографические характеристики, а также данные по терапии и исходам.Результаты. В исследование для анализа было включено 573 больных, 65,6 % из них составили мужчины. Средний возраст пациентов на момент постановки диагноза мПКР составил 63,1 года, при этом 14,5% были в возрасте >75 лет. 72% прошли хирургическое лечение по поводу первичной опухоли; светлоклеточный и несветлоклеточный рак был выявлен у 84% и 16% пациентов, соответственно.Лекарственная терапия проводилась 307 (54%) пациентам. Медиана продолжительности всех линий терапии составила 10 месяцев (95% ДИ 7,6-12,4). Наиболее часто применявшимся вариантом лечения было назначение интерферона (частота — 161 раз в любой из линий или на различных этапах лечения). Таргетная терапия проводилась у 160 (52,1%) пациентов, из них в качестве первой линии таргетную терапию получили 112 пациентов. 87 (28,3%) больных получили >2 линий терапии. 3-летняя ОВ составила 21 %, а медиана ОВ — 12 месяцев (95 % ДИ 11,1-12,9). Медиана ОВ в группах получивших и не получивших терапию пациентов составила 15,1 и 6,9 месяца, соответственно (Р<0,0001). Продолжительность жизни пациентов, прошедших вторую линию терапии (медиана — 18,4 месяца), была значительно дольше, чем у пациентов, получивших только первую линию терапии (10,9 месяца, Р<0,001).Выводы. Показатели ОВ в исследовании RENSUR3 являются неудовлетворительными, что, по-видимому, можно объяснить назначением лекарственного лечения только половине пациентов, низкой частотой применения таргетных препаратов, редким назначением таргетной терапии во второй и последующих линиях при прогрессировании болезни. Внедрение новейших вариантов лекарственного лечения, в том числе ингибиторов контрольных точек, будет способствовать улучшению продолжительности жизни больных

Продолжительность жизни больных метастатическим почечно-клеточным раком в Российской Федерации: результаты многоцентрового регистрового исследования RENSUR3

Background. Overall survival (OS) data obtained in patients with metastatic renal cell carcinoma (mRCC) in real-world settings are rarely published. The objective of the RENSUR3 registry study was to collect information on the use of various therapeutic options for mRCC in real-world clinical practice and assess OS in a Russian population.Methods. Patients were retrospectively identified at 8 cancer centres in different Russian regions and enrolled in the study if the diagnosis of mRCC had been made in the period from January 2015 to December 2016. Anonymous data were collected online, the registry contained demographic characteristics and treatment and outcome data.Results. The study had 573 subjects included in the analysis. The average age of patients at mRCC diagnosis was 63.1 years; 14.5 % of them were aged > 75 years. 65.6 % of the subjects were men; 72% had received surgical treatment for the primary tumour; clear cell and non-clear cell carcinomas were detected in 84 % and 16 % of the patients, respectively.Drug therapy was used in 307 patients (54%). The median duration of any line of therapy was 10 months (95% CI 7.6-12.4). The most frequent treatment option was interferon (administered 161 times as part of any line of therapy or at different stages of treatment). Targeted therapy was given to 160 patients (52.1%), 112 of whom received it as first-line therapy. 87 subjects (28.3%) received > 2 lines of therapy. The 3-year OS rate was 21%, and the median OS was 12 months (95% CI 11.1-12.9). The median OS in the therapy and no therapy groups was 15.1 months and 6.9 months, respectively (Р<0.0001). The median life expectancy in patients receiving second-line therapy (median 18.4 months) was significantly higher than in patients treated with first-line therapy only (10.9 months, Р<0.001).Conclusions: The OS results of the RENSUR3 study are unsatisfactory, which apparently can be explained by the fact that drug therapy was used in only half the patients, the infrequent use of targeted drugs, and the rare administration of targeted therapy for second and subsequent lines of therapy in patients with progressive disease. Introduction of the latest drug therapy options, including checkpoint inhibitors, will help improve patients» life expectancy.Введение. Данные по общей выживаемости (ОВ) пациентов с метастатическим почечно-клеточным раком (мПКР) в реальной жизни публикуются редко. Задача регистрового исследования RENSUR3 заключалась в сборе сведений по применению разных вариантов терапии при мПКР в условиях реальной клинической практики и оценке ОВ в популяции российских пациентов.Методы. Пациентов ретроспективно идентифицировали в 8 онкологических центрах в разных регионах России и включали в исследование, если диагноз мПКР был установлен в период с января 2015 г. по декабрь 2016 г. Анонимные сведения собирали онлайн, регистр охватывал демографические характеристики, а также данные по терапии и исходам.Результаты. В исследование для анализа было включено 573 больных, 65,6 % из них составили мужчины. Средний возраст пациентов на момент постановки диагноза мПКР составил 63,1 года, при этом 14,5% были в возрасте >75 лет. 72% прошли хирургическое лечение по поводу первичной опухоли; светлоклеточный и несветлоклеточный рак был выявлен у 84% и 16% пациентов, соответственно.Лекарственная терапия проводилась 307 (54%) пациентам. Медиана продолжительности всех линий терапии составила 10 месяцев (95% ДИ 7,6-12,4). Наиболее часто применявшимся вариантом лечения было назначение интерферона (частота — 161 раз в любой из линий или на различных этапах лечения). Таргетная терапия проводилась у 160 (52,1%) пациентов, из них в качестве первой линии таргетную терапию получили 112 пациентов. 87 (28,3%) больных получили >2 линий терапии. 3-летняя ОВ составила 21 %, а медиана ОВ — 12 месяцев (95 % ДИ 11,1-12,9). Медиана ОВ в группах получивших и не получивших терапию пациентов составила 15,1 и 6,9 месяца, соответственно (Р<0,0001). Продолжительность жизни пациентов, прошедших вторую линию терапии (медиана — 18,4 месяца), была значительно дольше, чем у пациентов, получивших только первую линию терапии (10,9 месяца, Р<0,001).Выводы. Показатели ОВ в исследовании RENSUR3 являются неудовлетворительными, что, по-видимому, можно объяснить назначением лекарственного лечения только половине пациентов, низкой частотой применения таргетных препаратов, редким назначением таргетной терапии во второй и последующих линиях при прогрессировании болезни. Внедрение новейших вариантов лекарственного лечения, в том числе ингибиторов контрольных точек, будет способствовать улучшению продолжительности жизни больных

Эффективность и безопасность эрибулина при различных подтипах рака молочной железы: данные из реальной клинической практики в России

The article presents a pooled experience of the use of eribulin in the real clinical practice of treatment of metastatic breast cancer in Russian oncological institutions. The effectiveness of the drug in monotherapy with HER2‑negative breast cancer was analyzed, groups of patients with most effective use of eribulin were identified depending on the localization of metastases, the most effective lines of therapy. The effectiveness of the drug in combination with trastuzumab in HER2‑positive breast cancer is described, as well as toxic reactions. В статье представлен обобщенный опыт применения эрибулина в реальной клинической практике онкологических учреждений РФ при метастатическом раке молочной железы. Проанализирована эффективность препарата в монотерапии при HER2-отрицательном раке молочных желез, выделены группы больных в зависимости от локализации метастазов, линии терапии, в которых препарат оказался максимально эффективным. Описана эффективность препарата в комбинации с трастузумабом при HER2-положительном раке молочной железы, а также токсические реакции.