Influence of Aromatic and Aliphatic Moieties on Thrombin Inhibitors Potency

Thrombin is a plasma serine protease that plays a key role in coagulation and hemostasis but also in thromboembolic diseases. Direct thrombin inhibitors could be beneficial for future anticoagulant therapy in the prophylaxis of venous and arterial thrombosis as well as myocardial infarction. To design the efficient thrombin inhibitors we have synthesized and studied peptide-based inhibitors resistant to enzymatic degradation. Compounds with general formula X-DArg-D-Phe-OMe, where X = residue of 3-[6-ethyl-7-hydroxy-3-(4-methyl-thiazol-2-yl)-4-oxo-4H-chromen-2-yl]-propionic acid (chromone) and lauric acid were synthesized by classic methods of peptides synthesis in solution. The comparative inhibitory analysis of prepared compounds in relation to thrombin was conducted. The analysis of the inhibition effect of the peptide with retro-D-sequence modified by residues of natural organic compounds (chromone or fatty acid moiety) has demonstrated that modification with the fatty acid residue appeared to be the most successful one. Introduction of lauric acid residue (Ki = 1,76 μM) maximally increased the inhibition effect. These findings establish an important role of fatty moiety in structure of inhibitors in preferential binding and inhibition of thrombin active side

Public awareness on natural and technological hazards as a key for safety: the BeSafeNet initiative contribution.

Natural and technological hazards cause great human and economic losses. Furthermore, as happened with the Great East Japan earthquake and tsunami in 2011, natural hazards can trigger technological accidents, introducing an additional negative effect on people and environment and requiring a more comprehensive risk assessment and emergency planning. If we cannot prevent many of these hazards, we can try to minimize their potential consequences, in particular by informing people about the nature of hazard and its possible consequences for specific regions. General public behavior is an important factor in the success of any planning and providing it with clear explanations of all pertinent aspect of hazards is a prerequisite to foster a culture of safety supporting the necessary preventive actions.The BeSafeNet initiative, promoted by the EUR-OPA Major Hazards Agreement of the Council of Europe, has as a main aim, to better protect people from hazards through better informing them on the causes and the consequences of natural and technological hazards. Distributing widely such knowledge will help people to better understand the potential risks and consequently to better protect themselves against them

Double difiusion in Ar-N2 Binary gas system at the constant value of temperature gradient

An experimental study of the diffusion-gravitational convection transition boundary in an Ar-N2 binary system at different pressures and a constant temperature gradient is performed. It is shown that the diflusion is replaced by the gravitational convection at a pressure p 0:5 MPa. In terms of the stability theory, a perturbation boundary line is determined, dividing the Rayleigh numbers plane into the regions of the diflusion and the convective mass transfer. The experimental data agree well with the theoretical values

Аттракторы биологического сигнального поля волков (canis lupus) в экспериментальных условиях

The concept of biological signal field is expanded to information field of biotope, considering as attractors different objects in biotope space that organize the activity of animals. The most effective attractors are the objects of environment that noticeably stand out for general background. The observed changes during the time in spatial activity of wolves are associated with changes in system of attractors and biological signal field - system of attractors of the second order being formed by population itself.Понятие «биологическое сигнальное поле» расширено до информационного поля биотопа, в качестве аттракторов учитываются различные объекты в пространстве биотопа, организующие активность животных. Наиболее эффективными аттракторами являются объекты окружающей среды, которые заметно выделяются из общего фона. Наблюдаемые изменения пространственной активности волков во времени связаны с изменением системы действующих аттракторов и биологического сигнального поля - системы аттракторов второго порядка, формируемой самой популяцией

ВОЗМОЖНОСТИ УЛЬТРАЗВУКОВОЙ НАВИГАЦИИ ДЛЯ РАДИОЧАСТОТНОЙ ДЕНЕРВАЦИИ МЕЖПОЗВОНКОВЫХ СУСТАВОВ ПОЯСНИЧНОГО ОТДЕЛА ПОЗВОНОЧНИКА

The aim of the study was to evaluate the possibility of US navigation for Radiofrequency denervation (RFD) of the lumbar facets.Material and methods. The authors performed a prospective controlled cohort study which included 50 patients with chronic pain syndrome who underwent RFD LIII-SI facets on both sides. The main group (US) included 25 patients, who underwent US guided navigation with FScontrol of the correct placement of the cannula prior to ablation. In the control group (FS) the RFD was performed only under FS control. Patients were selected after preliminary test block of medial branch with 50% pain reduction from the baseline. Patients with overweight, spinal deformity, pronounced degenerative changes, spinal stenosis and developmental anomalies were not included in the study. For the evaluation of outcomes, the numeric pain scale NRS-11 and the Oswestry index (ODI) were used, the accuracy of the cannula position was assessed and factors determining the accuracy were searched.Results. As a result of the intervention, there was a significant decrease of NRS-11 and ODI criteria in both groups (p0.001), a positive outcome was achieved in 18 (72%) of US patients and 16 (64%) of FS patients, p = 0.564. Of the 200 attempts to position the cannula under the ultrasound control, 169 (84.5%) were successful, in most cases (187 out of 200, 93.5%) at least 3 attempts were required to reposition the cannula. The average time for performing the procedure under the ultrasound control was 47.3±1.13 minutes. The facet angle and procedure level were defined as predictors of the cannula positioning accuracy, odds ratio 0.93 (95% CI 0.894–0.963) and 0.51 (95% CI 0.32–0.805), respectively.Conclusion. RFD of lumbar facet under ultrasound navigation allows to achieve a relatively high accuracy of the cannula position into the zone of passage of the articular branch. The navigation capabilities are reduced at the level of LV and SI vertebrae due to structural features of the joints, namely coronary orientation of the facets with the formation of a narrow space between the transverse and upper articular process, which create difficulties for scanning. The disadvantage of ultrasound control is the lengthy procedure and the need for repeated reinsertion of the cannulae worsening the patient’s tolerance of procedure.Цель исследования — оценить возможности использования УЗ-навигации при выполнении радиочастотной денервации (РЧД) межпозвонковых суставов (МПС) поясничного отдела позвоночника.Материал и методы. Выполнено проспективное контролируемое когортное исследование. В исследование включено 50 пациентов с хроническим болевым синдромом, которым выполнялась РЧД МПС LIII-SI позвонков с двух сторон. Пациенты были поделены на две группы. В основную группу вошло 25 пациентов, которым РЧД проводилась под ультразвуковой навигацией с ФС-контролем правильности установки канюль перед началом абляции. В контрольной группе, состоящей также из 25 пациентов, РЧД проводилась только под ФС-контролем. Отбор пациентов проводился на основании предварительной тестовой блокады МПС при условии снижении боли на 50% от исходного. Для оценки исходов использовалась цифровая шкала боли NRS-11 и индекс Освестри (OID), оценивалась точность попадания канюлей в необходимую зону, проводился поиск факторов, влияющих на точность попадания.Результаты. В результате вмешательства произошло значимое снижение исследуемых показателей в обеих группах (p0,001), положительный исход достигнут у 18 (72%) пациентов основной группы и 16 (64%) контрольной группы, различия не были статистически значимыми (p = 0,564). Из 200 попыток проведения канюль под УЗ-контролем 169 (84, 5%) были успешными при ФС-контроле, в большинстве случаев (187 из 200, 93,5%) требовалось не менее 3 попыток переустановки канюли. Среднее время выполнения вмешательства под УЗ-контролем составило 47,3±1,13 мин. Фасеточный угол и уровень вмешательства определены в качестве предикторов точности попадания, отношение шансов 0,93 при 95% доверительном интервале 0, 894–0,963, и 0,51 при 0,32–0,805 соответственно.Выводы. Выполнение РЧД МПС поясничного отдела позвоночника с использованием УЗ-навигации позволяет достигнуть относительно высокой точности попадания канюлей в зону прохождения артикулярной ветви. Возможности навигации снижаются на уровне LV и SI позвонков, что определяется наличием особенностей строения МПС в виде коронарной ориентации фасеток с формированием узкого пространства между поперечным и верхним суставным отростком, затрудняющим сканирование. Недостатком УЗ-контроля является длительность процедуры и необходимость неоднократной переустановки канюль, ухудшающих переносимость пациентом вмешательства

РЕЗУЛЬТАТЫ ТРАНСФОРАМИНАЛЬНОЙ ЭНДОСКОПИЧЕСКОЙ ДИСКЭКТОМИИ ПРИ ГРЫЖАХ МЕЖПОЗВОНКОВЫХ ДИСКОВ ПОЯСНИЧНО-КРЕСТЦОВОГО ОТДЕЛА ПОЗВОНОЧНИКА

Introduction. Lumbar disc herniation is a frequent pathology and surgical target. Endoscopic discectomy becomes more popular due to minimally invasive surgical technique. There is a deficit of scientific papers dedicated to analysis of potential for endoscopic discectomy depending on the specifics of spinal anatomy and degenerative changes.The purpose of the study was to evaluate the efficacy of transforaminal endoscopic discectomy (TED) in comparison with microdiscectomy (MD) and to specify factors determining complications and failures.Materials and methods. The authors performed randomized controlled study where main group of patients included data on prospective examination of 101 patients after TED procedure for lumbar intervertebral disc herniation. Age of patients ranged from 19 to 81 years with average of 41,4±12,6 years. Control group included data of retrospective examination of 153 patients that were operated by the same surgeon in the period from 201 till 2104 with microdiscectomy procedure. Age of patients ranged from 18 to 77 years with average of 47,8±11,3 years. Inclusion criteria were as follows: surgical procedure at the same level of the primary intervertebral herniation. Exclusion criteria were: degenerative spinal canal stenosis, spondylolisthesis, spine deformity.Results. Clinical outcomes after TED demonstrated no difference from MD procedure. No factors of significant influence on outcomes after surgical procedure were observed. The main group was characterized by more cases of revisions and conversions of endoscopic into open procedures (13,9%) which was related to mistakes in transforaminal approach due to features of intervertebral joints and foramina anatomy resulting in impossibility to achieve adequate spinal canal decompression.Conclusion. Transforaminal endoscopic discectomy is an effective and safe method of lumbar intervertebral herniation treatment. Complications and failures during learning curve of endoscopic procedure are associated with technique drawbacks as well as with mistakes in planning and performing the approach. Congenital alignment of lumbar spine with specific patterns of facets and foramina anatomy dictate technical difficulties with transforaminal approach. Актуальность. Эндоскопическая дискэктомия завоевывает все бóльшую популярность в связи с наименьшей травматичностью доступа. Существует дефицит научных работ, анализирующих возможности ее применения в зависимости от особенностей анатомии позвоночника и дегенеративно-дистрофических изменений.Цель исследования — оценить эффективность трансфораминальной эндоскопической дискэктомии в сравнении с открытой дискэктомией, а также определить факторы, влияющие на развитие осложнений и неудовлетворительные результаты.Материал и методы. Выполнено рандомизированное контролируемое когортное исследование. В основную группу были включены данные проспективного исследования 101 пациента, прооперированных по поводу грыж межпозвонковых дисков поясничного отдела позвоночника с использованием трансфораминальной эндоскопической дискэктомии. Возраст пациентов варьировал от 19 до 81 года, в среднем составил 41,4±12,6 лет. В контрольную группу вошли данные ретроспективного обследования 153 пациентов, оперированных тем же хирургом в 2013–2014 гг. в объеме микродискэктомии. Возраст пациентов варьировал от 18 до 77 лет, в среднем — 47,8±11,3 лет. Критерием включения в исследование являлось хирургическое вмешательство на одном уровне по поводу первичной грыжи МПД. Критерии исключения: дегенеративный стеноз позвоночного канала, спондилолистез, деформация позвоночника.Результаты. Клинические результаты эндоскопической дискэктомии не отличались от результатов микродискэктомии. Факторов, значимо влияющих на результаты оперативного лечения в обеих группах, не выявлено. В основной группе было больше повторных операций и конверсий эндоскопических вмешательств в открытые (13,9%). Это связано с ошибками выполнения трансфораминального доступа вследствие конституциональных особенностей анатомии межпозвонковых суставов и отверстий, в результате которого визуализация и адекватная декомпрессия позвоночного канала были невозможны.Выводы. Трансфораминальная эндоскопическая дискэктомия является эффективным и безопасным методом хирургического лечения межпозвонковых грыж поясничного отдела позвоночника. Осложнения и неудачные результаты оперативного лечения во время освоения эндоскопической хирургии определяются недостатками хирургической техники, а также ошибками в планировании и выполнении трансфораминального доступа. Особенности конституции позвоночника в виде гиперили гиполордоза с характерными изменениями анатомии фасеточных суставов и межпозвонковых отверстий оперелеляют технические трудности при трансфораминальном доступе.

An integrative taxonomic analysis reveals a new species of lotic Hynobius salamander from Japan

We examine the phylogenetic structure and morphological differentiation within the Hynobius kimurae–H. boulengeri species complex—a widely-distributed group of stream-breeding hynobiid salamanders, inhabiting montane areas of western, central and eastern parts of Honshu Island, Japan. Phylogenetic relationships were assessed based on analyses of mitochondrial (mtDNA) and nuclear (nuDNA) gene fragments for a total of 51 samples representing 23 localities covering the entire range of the species complex. Morphological study included one-way analysis of variance (ANOVA) and principal components analysis (PCA) analyses of 26 morphometric and six meristic characters for 38 adult specimens of H. kimurae and three adult specimens of H. boulengeri. MtDNA genealogy supported monophyly of the H. kimurae–H. boulengeri complex, which is sister to all other Hynobius except H. retardatus. The complex is subdivided into three major clades, corresponding to the Eastern (Clade I) and Western (Clade II) populations of H. kimurae sensu lato, and to H. boulengeri (Clade III). Monophyly of H. kimurae sensu lato is only moderately supported by mtDNA, while nuDNA suggested that the Western form of H. kimurae is closer to H. boulengeri than to the eastern form. The time of the split of the H. kimurae–H. boulengeri complex is estimated as late Miocene and coincides with intensive crust movement in western Japan. Divergence between Clades I and II took place in early Pliocene and was likely influenced by the uplift of Central Japanese Highlands. All three clades were found to be different in a number of morphological characters, allowing us to describe the eastern form of H. kimurae as a new species, Hynobius fossigenus sp. nov

Magneto-Conductance Anisotropy and Interference Effects in Variable Range Hopping

We investigate the magneto-conductance (MC) anisotropy in the variable range hopping regime, caused by quantum interference effects in three dimensions. When no spin-orbit scattering is included, there is an increase in the localization length (as in two dimensions), producing a large positive MC. By contrast, with spin-orbit scattering present, there is no change in the localization length, and only a small increase in the overall tunneling amplitude. The numerical data for small magnetic fields $B$, and hopping lengths $t$, can be collapsed by using scaling variables $B_\perp t^{3/2}$, and $B_\parallel t$ in the perpendicular and parallel field orientations respectively. This is in agreement with the flux through a `cigar'--shaped region with a diffusive transverse dimension proportional to $\sqrt{t}$. If a single hop dominates the conductivity of the sample, this leads to a characteristic orientational `finger print' for the MC anisotropy. However, we estimate that many hops contribute to conductivity of typical samples, and thus averaging over critical hop orientations renders the bulk sample isotropic, as seen experimentally. Anisotropy appears for thin films, when the length of the hop is comparable to the thickness. The hops are then restricted to align with the sample plane, leading to different MC behaviors parallel and perpendicular to it, even after averaging over many hops. We predict the variations of such anisotropy with both the hop size and the magnetic field strength. An orientational bias produced by strong electric fields will also lead to MC anisotropy.Comment: 24 pages, RevTex, 9 postscript figures uuencoded Submitted to PR