ХИРУРГИЧЕСКОЕ ЛЕЧЕНИЕ СТОПЫ ШАРКО, ОСЛОЖНЕННОЙ ФЛЕГМОНОЙ

The article presents a clinical case of successful surgical treatment of phlegmon in the case of diabetic neuroosteoarthropathy (Charcot foot). This observation illustrates the clinical features, diagnostic algorithm and potential of modern complex treatment of the most  rare form of diabetic foot syndrome which is diabetic neuroosteoarthropathy.В статье приводится клинический случай успешного хирургического лечения флегмоны стопы на фоне диабетической нейроостеоартропатии (стопа Шарко). Данное наблюдение иллюстрирует особенности клинического течения, диагностического алгоритма и возможности современного комплексного лечения наиболее редко встречающейся формы синдрома диабетической стопы, какой является диабетическая нейроостеоартропатия

Comparison of Internal Ribosome Entry Site (IRES) and Furin-2A (F2A) for Monoclonal Antibody Expression Level and Quality in CHO Cells

10.1371/journal.pone.0063247PLoS ONE85

CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in ⩾50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC50 values of 2–7 ng ml−1. MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours

Отдаленные результаты комплексной терапии больной сахарным диабетом 2 типа и двусторонней нейроостеоартропатией

Diabetic neuroosteoarthropathy (DNOAP) is a serious diabetes melitus complication leading to the limb loss. There was developed several ways for surgical correction of foot deformation at DNOAP in recent years, however, there is no much known about their use long-term results. This article presents the successful complex treatment and 10-years outcomes results in patient with type 2 diabetes and both feet deformation due to the DNOAP.Диабетическая нейроостеоартропатия (ДНОАП) – тяжелое осложнение сахарного диабета (СД), которое может привести к потере конечности. В последние годы было разработано несколько вариантов хирургической коррекции деформаций стопы при ДНОАП, однако об отдаленных результатах их использования пока что известно мало. В данной статье мы представляем результаты 10-летнего наблюдения и успешного комплексного лечения пациентки с СД 2 типа и деформацией обеих стоп на фоне ДНОАП

Методы оценки размеров раневого дефекта при синдроме диабетической стопы

Object. The study of the informativeness by various methods of visualizing the dimensions of wound defects and the dynamics of their healing in patients with diabetic foot syndrome (DFS).Materials and Methods. The descriptive research analyzed various methods for determining the size of wounds in 77 patients with DFS. 63 (81.8 %) patients (1st group) were performed classical planimetry by film using. The wound size at 6 (7.8 %) patients (2nd group) was estimated by using a computer program, 8 (10.4 %) patients (3d group) underwent magnetic resonance imaging (MRI) their feet.Results. In the course of the study, the median area of wounds in Group 1 patients were 25.0 [16.2; 44.5] cm2, median depth — 3.3 [1.5; 6.5] cm. It was required about 15–20 minutes of the expert work. The median area of wounds by patients Group 2, measured with the mobile application V2F, was 8.95 [6.8; 10.6] cm2. The depth determined by the same method was 0.25 [0.2; 0.5] cm. The study duration amount to 5 minutes approximately. The 3d patients Group that was measured with MRI had wound defects depth equal to 3.2 [2.6; 4.5] cm, wound area - 23.5 [12.3; 55.3] cm2. This study duration was similar to the standard MRI protocol.Conclusion. The planimetric method of wound size analysis is a routine way for assessing the dynamics of the wound defects state, its size and depth. Determining the size of wounds with special software is rather quick and simple method, but it allows to evaluate only the planar characteristics of the wound and has a high error. The MRI procedure of a wound with an alginate dressing allows to reliably estimate the volume of wound defect and exclude the presence of a hidden infection focus.Цель. Изучение информативности различных методов визуализации размеров раневых дефектов и динамики их заживления у пациентов с синдромом диабетической стопы (СДС).Материалы и методы. В описательном исследовании были проанализированы различные методы определения размеров ран у 77 пациентов с СДС. 63 (81,8 %) пациентам (группа 1) провели классическую планиметрию с использованием пленки. У 6 (7,8 %) человек (группа 2) размеры раны оценивали с помощью компьютерной программы. 8 (10,4 %) больным (группа 3) проводили МРТ стопы. Результаты. В ходе проведенного исследования медиана площади ран у пациентов группы 1 составляла 25,0 [16,2; 44,5] см2, медиана глубины — 3,3 [1,5; 6,5] см. На проведение данного исследования в среднем требовалось около 15–20 минут специалиста. У пациентов группы 2 медиана площади ран, измеренная с помощью мобильного приложения V2F, составляла 8,95 [6,8; 10,6] см2. Глубина, определенная аналогичным методом, – 0,25 [0,2; 0,5] см. Длительность исследования составляла около 5 минут. У больных группы 3 медиана глубины раневых дефектов, измеренная при помощи МРТ, составляла 3,2 [2,6; 4,5] см, площадь раны — 23,5 [12,3; 55,3] см2. Продолжительность данного исследования аналогична стандартному протоколу МРТ.Заключение. Исследование размеров ран планиметрическим методом является рутинным способом оценки динамики состояния раневого дефекта, его размеров и глубины. Определение размеров ран при помощи специального программного обеспечения – достаточно быстрый и простой метод, однако он позволяет оценить лишь плоскостные характеристики раны и отличается высокой погрешностью. Методика проведения МРТ раны с альгинатной повязкой позволяет достоверно оценить объем раневого дефекта и исключить наличие скрытого очага инфекции.

Insights into the Transposable Mobilome of Paracoccus spp. (Alphaproteobacteria)

Several trap plasmids (enabling positive selection of transposition events) were used to identify a pool of functional transposable elements (TEs) residing in bacteria of the genus Paracoccus (Alphaproteobacteria). Complex analysis of 25 strains representing 20 species of this genus led to the capture and characterization of (i) 37 insertion sequences (ISs) representing 9 IS families (IS3, IS5, IS6, IS21, IS66, IS256, IS1182, IS1380 and IS1634), (ii) a composite transposon Tn6097 generated by two copies of the ISPfe2 (IS1634 family) containing two predicted genetic modules, involved in the arginine deiminase pathway and daunorubicin/doxorubicin resistance, (iii) 3 non-composite transposons of the Tn3 family, including Tn5393 carrying streptomycin resistance and (iv) a transposable genomic island TnPpa1 (45 kb). Some of the elements (e.g. Tn5393, Tn6097 and ISs of the IS903 group of the IS5 family) were shown to contain strong promoters able to drive transcription of genes placed downstream of the target site of transposition. Through the application of trap plasmid pCM132TC, containing a promoterless tetracycline resistance reporter gene, we identified five ways in which transposition can supply promoters to transcriptionally silent genes. Besides highlighting the diversity and specific features of several TEs, the analyses performed in this study have provided novel and interesting information on (i) the dynamics of the process of transposition (e.g. the unusually high frequency of transposition of TnPpa1) and (ii) structural changes in DNA mediated by transposition (e.g. the generation of large deletions in the recipient molecule upon transposition of ISPve1 of the IS21 family). We also demonstrated the great potential of TEs and transposition in the generation of diverse phenotypes as well as in the natural amplification and dissemination of genetic information (of adaptative value) by horizontal gene transfer, which is considered the driving force of bacterial evolution

Quantification of the relative contribution of the different right ventricular wall motion components to right ventricular ejection fraction

Abstract Three major mechanisms contribute to right ventricular (RV) pump function: (i) shortening of the longitudinal axis with traction of the tricuspid annulus towards the apex; (ii) inward movement of the RV free wall; (iii) bulging of the interventricular septum into the RV and stretching the free wall over the septum. The relative contribution of the aforementioned mechanisms to RV pump function may change in different pathological conditions. Our aim was to develop a custom method to separately assess the extent of longitudinal, radial and anteroposterior displacement of the RV walls and to quantify their relative contribution to global RV ejection fraction using 3D data sets obtained by echocardiography. Accordingly, we decomposed the movement of the exported RV beutel wall in a vertex based manner. The volumes of the beutels accounting for the RV wall motion in only one direction (either longitudinal, radial, or anteroposterior) were calculated at each time frame using the signed tetrahedron method. Then, the relative contribution of the RV wall motion along the three different directions to global RV ejection fraction was calculated either as the ratio of the given direction’s ejection fraction to global ejection fraction and as the frame-by-frame RV volume change (∆V/∆t) along the three motion directions. The ReVISION (Right VentrIcular Separate wall motIon quantificatiON) method may contribute to a better understanding of the pathophysiology of RV mechanical adaptations to different loading conditions and diseases

Methylobacterium Genome Sequences: A Reference Blueprint to Investigate Microbial Metabolism of C1 Compounds from Natural and Industrial Sources

Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. The genomes of two pink-pigmented facultative methylotrophic bacteria of the Alpha-proteobacterial genus Methylobacterium, the reference species Methylobacterium extorquens strain AM1 and the dichloromethane-degrading strain DM4, were compared. Methodology/Principal Findings The 6.88 Mb genome of strain AM1 comprises a 5.51 Mb chromosome, a 1.26 Mb megaplasmid and three plasmids, while the 6.12 Mb genome of strain DM4 features a 5.94 Mb chromosome and two plasmids. The chromosomes are highly syntenic and share a large majority of genes, while plasmids are mostly strain-specific, with the exception of a 130 kb region of the strain AM1 megaplasmid which is syntenic to a chromosomal region of strain DM4. Both genomes contain large sets of insertion elements, many of them strain-specific, suggesting an important potential for genomic plasticity. Most of the genomic determinants associated with methylotrophy are nearly identical, with two exceptions that illustrate the metabolic and genomic versatility of Methylobacterium. A 126 kb dichloromethane utilization (dcm) gene cluster is essential for the ability of strain DM4 to use DCM as the sole carbon and energy source for growth and is unique to strain DM4. The methylamine utilization (mau) gene cluster is only found in strain AM1, indicating that strain DM4 employs an alternative system for growth with methylamine. The dcm and mau clusters represent two of the chromosomal genomic islands (AM1: 28; DM4: 17) that were defined. The mau cluster is flanked by mobile elements, but the dcm cluster disrupts a gene annotated as chelatase and for which we propose the name “island integration determinant” (iid).Conclusion/Significance These two genome sequences provide a platform for intra- and interspecies genomic comparisons in the genus Methylobacterium, and for investigations of the adaptive mechanisms which allow bacterial lineages to acquire methylotrophic lifestyles.Organismic and Evolutionary Biolog

Biology of moderately halophilic aerobic bacteria

The moderately halophilic heterotrophic aerobic bacteria form a diverse group of microorganisms. The property of halophilism is widespread within the bacterial domain. Bacterial halophiles are abundant in environments such as salt lakes, saline soils, and salted food products. Most species keep their intracellular ionic concentrations at low levels while synthesizing or accumulating organic solutes to provide osmotic equilibrium of the cytoplasm with the surrounding medium. Complex mechanisms of adjustment of the intracellular environments and the properties of the cytoplasmic membrane enable rapid adaptation to changes in the salt concentration of the environment. Approaches to the study of genetic processes have recently been developed for several moderate halophiles, opening the way toward an understanding of haloadaptation at the molecular level. The new information obtained is also expected to contribute to the development of novel biotechnological uses for these organisms