On the vibron dressing in the α\alpha--helicoidal macromolecular chains

We present a study of the physical properties of the vibrational excitation in $\alpha$--helicoidal macromolecular chains, caused by the interaction with acoustical and optical phonon modes. The influence of the temperature and the basic system parameters on the vibron dressing has been analyzed by employing the simple mean--field approach based on the variational extension of the Lang--Firsov unitary transformation. Applied approach predicts a region in system parameter space where one takes place an abrupt transition from partially dressed (light and mobile) to fully dressed (immobile) vibron states. We found that the boundary of this region depends on system temperature and type of bond among structural elements in the macromolecular chain.Comment: 22 pages, 12 figures, title changed, the interaction with optical phonon modes jointly with acoustical ones added, consideration significantly enlarged, references added, the paper develops the results of arxiv:1210.3918, accepted for publication in Chinese Physics

Безопасность и эффективность 23-валентной полисахаридной пневмококковой вакцины у больных системной красной волчанкой

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy > 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs <1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated <1 year before immunization. Further long-term prospective studies in large patient cohorts are required.Цель исследования – изучение безопасности и эффективности 23-валентной полисахаридной пневмококковой вакцины (ППВ-23) у больных системной красной волчанкой (СКВ).Пациенты и методы. В исследование включено 75 пациентов с достоверным диагнозом СКВ в возрасте 19–68 лет, 10 (13%) из них имели высокую активность СКВ, 18 (24%) – среднюю, 42 (56%) – низкую, у 5 (7%) – выявлена ремиссия заболевания. ППВ-23 вводили подкожно в разовой дозе 0,5 мл. У 60 пациентов срок наблюдения составлял ≥12 мес, у 15 – от 2 до 6 мес. Больных обследовали до и через 1, 3 и 12 мес после иммунизации.Результаты и обсуждение. У 38 (50,7%) пациентов отмечались стандартные местные вакцинальные реакции легкой и средней степени выраженности, у 1 (1,3%) – общая реакция легкой степени выраженности, у 2 (2,7%) – легкая диарея в течение 1 сут, у 1 (1,3%) – гиперергическая реакция по типу феномена Артюса, симптомы которой были купированы за 7 дней. На протяжении 12 мес наблюдения не выявлено ни одного случая обострения СКВ, достоверно связанного с вакцинацией, а также новых аутоиммунных феноменов. Через 1 год наблюдения число ответивших на вакцинацию составило 58%, не ответивших – 42%. Длительность и активность заболевания, возраст старше 50 лет, прием глюкокортикоидов в дозе >10 мг/сут значимо не влияли на вакцинальный ответ. Отмечено снижение иммунного ответа на фоне терапии генно-инженерными биологическими препаратами (ГИБП) по сравнению с отсутствием данного лечения (43 и 68% случаев соответственно), р=0,058. Различий на фоне применения ритуксимаба и белимумаба не установлено. Обнаружена тенденция к преобладанию ответивших на вакцинацию среди больных, получавших ГИБП <1 года до иммунизации, а также среди пациентов, которым эта терапия была инициирована после введения ППВ-23. Наблюдалась положительная динамика в виде уменьшения эпизодов пневмоний, острого и обострения хронического бронхита, синуситов.Заключение. Показаны достаточная иммуногенность, хорошая переносимость и клиническая эффективность ППВ-23 у больных СКВ, в том числе получавших комбинированную иммуносупрессивную терапию. Применение ГИБП уменьшает число пациентов с вакцинальным ответом. Если иммунизацию проводить до начала терапии ГИБП или на фоне такого лечения длительностью <1 года, то число ответивших на вакцинацию возрастает. Необходимы дальнейшие длительные проспективные исследования на больших выборках пациентов

Повреждение легких при антифосфолипидном синдроме

Functional lesions of organs depend on the size of a diseased vessel and frequently require the use of intensive therapy methods. The commonest manifestation of antiphospholipid syndrome (APS) is deep vein thrombosis of the leg and pulmonary thromboembolism (PTE).Objective: to estimate the frequency of lung lesions in primary APS (PAPS), secondary (in the presence of systemic lupus erythematosus (SLE)) and catastrophic APS and to assess a relationship between lung pathology and other clinical and laboratory manifestations of the disease.Subjects and methods. The study covered 372 patients followed up at the Institute of Rheumatology, Russian Academy of Medical Sciences, since 1990, of whom 290 and 82 patients had SLE and PAPS, respectively. Among the 290 patients with SLE, there were 96 males and 194 females. At the moment of the study, the patients’ age was 31.2±11.1 years and the duration of the disease was 8.6±7.2 years. The group of patients with PAPS comprised 20 males and 62 females. Their mean age was 35.6±9.9 years and the duration of the disease was 11.9±8.5 years. Thrombotic events were verified only by instrumental studies. Lung pathology was instrumentally confirmed; all the patients underwent lung X-ray study, if required, scintigraphy and computed tomography.Results. Lung lesion associated with the pathology of vessels was revealed in 28% of the examined patients (105/372). There were prevalent patients with PTE, followed by the development of lung infarcts, which was present in 96 (91%) of the 105 patients with pulmonary vascular pathology. Autopsy revealed pulmonary microangiopathy was in 12 patients, which was concurrent with focal pneumonia in 7 of them, with pneumonitis and exudative pleuritis in 5. Hemorrhagic alveolitis detected at autopsy in combination with occlusions of the pulmonary arterioles was in 3 patients who had been diagnosed as having thromboembolism of small branches of the pulmonary artery. Thrombosis of the pulmonary arterial trunk was detectable in 2 patients, both patients died from respiratory failure. All 105 patients with pulmonary vascular pathology had blood serological markers of APS. There was a combination of elevated levels of aKL and VA in 61% of cases and in 28.5% in the group of patients without pulmonary vascular pathology (OR = 3.92; [2.38-6.48]). The rate of vascular lung pathology increased in the presence of both blood aKL isotopes (IgG and IgM). The number of patients position in both aKL isotopes was 48% whereas in Group 2, that was 19.5% (OR = 3.76; [2.24-6.31]).Conclusion. More than a fourth of the patients with SLE and PAPS have pulmonary vascular pathology. The spectrum of pulmonary vascular diseases in SLE is broad and varies from thrombosis of the pulmonary arterial trunk to occlusive vascular lesion of the microcirculatory bed of the lung, and it is associated with aFL.Функциональные повреждения органов зависят от калибра пораженного сосуда и часто требуют применения методов интенсивной терапии. Наиболее частым проявлением АФС является тромбоз глубоких вен голеней и тромбоэмболии легочных артерий.Цель: оценить частоту поражения легких при первичном АФС, вторичном (на фоне СКВ) и катастрофическом АФС и связь между патологией легких и другими клинико-лабораторными проявлениями заболевания.Материал и методы. В исследование включены 372 больных, наблюдавшихся в Институте ревматологии РАМН с 1990 г., из которых 290 имели СКВ и 82 — ПАФС. Среди больных СКВ 96 из 290 были мужчины и 194 женщины. Возраст больных на момент исследования составлял 31,2±11,1 лет и длительность заболевания 8,6±7,2 лет. Группу больных с ПАФС составляли 20 мужчин и 62 женщины. Средний возраст был 35,6±9,9 лет и длительность заболевания — 11,9±8,5 лет. Тромботические исходы верифицировались только при инструментальном их подтверждении. Легочная патология подтверждалась инструментально, всем больным проводилась рентгенография легких, при необходимости сцинтиграфия и компьютерная томография легких.Результаты. Поражение легких, связанное с патологией сосудов, было выявлено у 28% (105 из 372) обследованных больных. Преобладало число больных с ТЭЛА и последующим развитием инфаркта легких, которая имела место у 96 из 105 (91%) больных c сосудистой патологией легких. Легочная микроанги-опатия была выявлена при аутопсии у 12 больных и у 7 из них она сочеталась с очаговой пневмонией, у 5 — с пневмонитом и экссудативным плевритом. Геморрагический альвеолит, выявленный на аутопсии, в сочетании с окклю-зиями артериол легких — у 3 больных, при жизни у них диагностировалась тромбоэмболия мелких ветвей легочной артерии. Тромбоз ствола легочной артерии определялся у 2 больных, оба пациента умерли из-за легочной недостаточности. Все 105 больных с сосудистой легочной патологией имели в крови серологические маркеры АФС. Сочетание повышенных уровней аКЛ и ВА отмечено в 61% случаев, тогда как в группе больных без сосудистой легочной патологии — в 28,5% (OR=3,92; [2,38—6,48]). Частота сосудистой патологии легких возрастала при наличии в крови обоих изотипов аКЛ (IgG; IgM). Число больных позитивных по обоим изотипам аКЛ в первой группе составило 48%, тогда как во второй — 19,5% (OR=3,76; [2,24—6,31]).Заключение. более одной четверти больных СКВ и ПАФС имеют патологию сосудов легких. Спектр легочной сосудистой патологии СКВ широк и варьирует от тромбоза ствола легочной артерии до окклюзивного поражения сосудов микроциркуляторного русла легких и ассоциируется с аФЛ

Differential Geometry for Model Independent Analysis of Images and Other Non-Euclidean Data: Recent Developments

This article provides an exposition of recent methodologies for nonparametric analysis of digital observations on images and other non-Euclidean objects. Fr\'echet means of distributions on metric spaces, such as manifolds and stratified spaces, have played an important role in this endeavor. Apart from theoretical issues of uniqueness of the Fr\'echet minimizer and the asymptotic distribution of the sample Fr\'echet mean under uniqueness, applications to image analysis are highlighted. In addition, nonparametric Bayes theory is brought to bear on the problems of density estimation and classification on manifolds

The Congenital Cataract-Linked G61C Mutation Destabilizes γD-Crystallin and Promotes Non-Native Aggregation

γD-crystallin is one of the major structural proteins in human eye lens. The solubility and stability of γD-crystallin play a crucial role in maintaining the optical properties of the lens during the life span of an individual. Previous study has shown that the inherited mutation G61C results in autosomal dominant congenital cataract. In this research, we studied the effects of the G61C mutation on γD-crystallin structure, stability and aggregation via biophysical methods. CD, intrinsic and extrinsic fluorescence spectroscopy indicated that the G61C mutation did not affect the native structure of γD-crystallin. The stability of γD-crystallin against heat- or GdnHCl-induced denaturation was significantly decreased by the mutation, while no influence was observed on the acid-induced unfolding. The mutation mainly affected the transition from the native state to the intermediate but not that from the intermediate to the unfolded or aggregated states. At high temperatures, both proteins were able to form aggregates, and the aggregation of the mutant was much more serious than the wild type protein at the same temperature. At body temperature and acidic conditions, the mutant was more prone to form amyloid-like fibrils. The aggregation-prone property of the mutant was not altered by the addition of reductive reagent. These results suggested that the decrease in protein stability followed by aggregation-prone property might be the major cause in the hereditary cataract induced by the G61C mutation

Antiphospholipide antibodies subtypes in systemic lupus erythematosus and antiphospholipid syndrome

Objective. То study frequency and clinical significance of different antiphospholipid antibodies (APHLA): anti- cardiolipin (АСА), anti-?2 glycoprotein (AB2), anti-annexin V (AAV) and autoantibodies to oxidized low density lipoproteins (AOLDPL) in pts with systemic lupus erythematosus (SLE) with and without antiphospholipid syndrome (APS). Material and methods. 68 pts (14 male, 54 female, mean age 35,2+11,4 years) followed up in the Institute оГ Rheumatology were included. 45 of them had SLE and 23 - primary APS. 24 from 45 SLE pts had signs of APS. Only instrumentally verified thromboembolic events were recorded. 43 from 68 (63,2%) pts had history of thrombosis. АСА, AB2, AAV and AOLDPL serum level was examined with immuno-enzyme assay. IgG АСА level was in the Institute of Rheumatology of RAMS and in the Institute of Rfeumatology of Warsaw. Lupus anticoagulant was tested with phospholipids-dependent method in platelet depleted plasma. Results. IgG АСА were more frequently revealed in the Institute of Rheumatology of RAMS and were associated with the presence of APS. In the Warsaw laboratory IgG positivity in SLE was revealed in 29%, in SLE+APS - in 33%, in primary APS - in 39%. in half of the pts IgG АСА level was doubtful or low-positive. Thromboembolic events were associated with the presence of IgG AB2 (mean level 0,292 U of OP, median 0,157, minimum - 0,049, maximum 0,994, interquartile dispersion 0,251). Mean level in the absence of thrombosis was 0, 178 U of OP (median 0,112, minimum - 0,440, maximum 0,834, interquartile dispersion 0,100), p=0,003 according to Mann-Whitney test. There was no statistical dependence between IgG АСА, IgG AAV and Ihrom- boembolic events but very high levels of antibodies were present in the group of pts with thromboses. There was a correlation between SLE activity and high AOLDPL level. Mean value of SLEDAI scale in 16 SLE pts with high AOLDPL level was 22,6+4,34 compared with 8,37+3,52 (p=0,000I) in 22 SLE pts not having these antibodies. Conclusion. Presence of IgG AB2 is associated with thromboses independently of their localization. Presence of AOLDPL was associated with disease activity