Orthopaedic, psychological, social and philosophical aspects of achondroplasia patients treated with the Ilizarov method

Introduction Achondroplasia is the most common skeletal dysplasia with limb shortening that can be symptomatically be treated with the Ilizarov method developed in the 20th century. Achondroplasia patients were shown to have medical and surgical possibilities for height increase with indications being controversial, and psychological and social implications to be considered. Objective The purpose of the study was to review our own data and reported findings on possibilities, results and complications of Ilizarov treatment of achondroplasia patients. Material and methods Outcomes of 750 achondroplasia patients treated at the Kurgan Ilizarov Center between 1976 and 2017 were reviewed. The patients’age ranged from 4 to 23 years. Results Long-term outcomes were followed up in all the cases. Radiography was used to assess limb elongation at follow-ups and MRI, MSCT and US were optional. Ten-to-fifteen-year follow-ups showed persisted length gain, early osteoarthritis of the hip and knee joints due to baseline articular changes, completely restructured femur and tibia at the distraction site, normal anatomy and area of muscle cross-section, normal structure and thickness of tibial muscles. Social and psychological profile appeared to improve. We have data from the patients who underwent limb lengthening 30 years ago. Many of them are employed, have family and children. Conclusion The findings suggest that achondroplasia patients, a comparatively small group of short statured people, have good reasons to feel empowered, get social support, make parents happy and contribute to the success of the country. The Ilizarov method has turned the idea of height increase into an accomplishment for benefits of doctors and patients being an achievement of orthopaedic world to address orthopaedic, social, psychological and philosophical issues

СОВРЕМЕННЫЕ МЕТОДЫ ИЗУЧЕНИЯ ДИСТРАКЦИОННОГО РЕГЕНЕРАТА С ПРИМЕНЕНИЕМ ЛУЧЕВОЙ ДИАГНОСТИКИ

The review presents the results of diagnostic imaging techniques for evaluation of distractional regenerate bone starting from classical polypositional radiography to modern imaging modalities such as magnetic resonance imaging and computed tomography. There are described the modifications of the known techniques for evaluation of regeneration bone with quantitative and qualitative analysis, the opinions of different authors about possibilities and problems of imaging practices. There are presented the problems and goals for more effective evaluation of new bone at different stages of limb lengthening with the focus on a wider application of modern imaging modalities at medical institutions. The review is based on dissertation work of K. A. Diachkov «Diagnostic imaging for detection of the rules of distractional regenerate bone formation and bone quality during limb lengthening». Literature review was performed using database of PubMed, Medline, Embase 12 Russian journals on traumatology and orthopaedics, diagnostic imaging 2007–2016. All articles on evaluation of distractional bone regeneration were reviewed.В представленном обзоре представлены данные о применении методов лучевой диагностики для изучения дистракционного регенерата, начиная с классической полипозиционной рентгенографии и заканчивая самыми современными методами визуализации, в том числе магнитно-резонансной и компьютерной томографии. Приведены данные о различных модификациях известных методик, проанализированы способы оценки регенерата при изучении его качественных и количественных показателей, рекомендации и мнения авторов о возможности и проблемах использованных методик. Указано на нерешенные вопросы и задачи для более эффективного исследования новообразованной кости в различные периоды удлинения конечности, на необходимость более широкого внедрения современной аппаратуры в лечебных учреждениях. Материал, использованный для подготовки обзора, взят из диссертации К. А. Дьячкова «Лучевая диагностика в выявлении закономерностей формирования дистракционного регенерата и качества кости при удлинении конечности», защищенной 15 февраля 2017 г. по специальности 14.01.13 «Лучевая диагностика, лучевая терапия» в диссертационном совете Д208.041.04 на базе ГБОУ ВО МГМСУ им. А. И. Евдокимова Минздрава России, научный консультант — заслуженный деятель науки Российской Федерации, доктор медицинских наук, профессор, член-корреспондент РАН Васильев Александр Юрьевич. Обзор литературы проведен на основании анализа данных базы РubMed, Medline, Embase 12 русскоязычных журналов по травматологии и ортопедии, лучевой диагностике. Рассматривались статьи за 2007–2016 гг. Анализировались все статьи, где рассматривались вопросы изучения дистракционного регенерата методами лучевой диагностики

Association of the Chromosome Replication Initiator DnaA with the Escherichia coli Inner Membrane In Vivo: Quantity and Mode of Binding

DnaA initiates chromosome replication in most known bacteria and its activity is controlled so that this event occurs only once every cell division cycle. ATP in the active ATP-DnaA is hydrolyzed after initiation and the resulting ADP is replaced with ATP on the verge of the next initiation. Two putative recycling mechanisms depend on the binding of DnaA either to the membrane or to specific chromosomal sites, promoting nucleotide dissociation. While there is no doubt that DnaA interacts with artificial membranes in vitro, it is still controversial as to whether it binds the cytoplasmic membrane in vivo. In this work we looked for DnaA-membrane interaction in E. coli cells by employing cell fractionation with both native and fluorescent DnaA hybrids. We show that about 10% of cellular DnaA is reproducibly membrane-associated. This small fraction might be physiologically significant and represent the free DnaA available for initiation, rather than the vast majority bound to the datA reservoir. Using the combination of mCherry with a variety of DnaA fragments, we demonstrate that the membrane binding function is delocalized on the surface of the protein’s domain III, rather than confined to a particular sequence. We propose a new binding-bending mechanism to explain the membrane-induced nucleotide release from DnaA. This mechanism would be fundamental to the initiation of replication

Ion association in concentrated NaCI brines from ambient to supercritical conditions: results from classical molecular dynamics simulations

Highly concentrated NaCl brines are important geothermal fluids; chloride complexation of metals in such brines increases the solubility of minerals and plays a fundamental role in the genesis of hydrothermal ore deposits. There is experimental evidence that the molecular nature of the NaCl–water system changes over the pressure–temperature range of the Earth's crust. A transition of concentrated NaCl–H(2)O brines to a "hydrous molten salt" at high P and T has been argued to stabilize an aqueous fluid phase in the deep crust. In this work, we have done molecular dynamic simulations using classical potentials to determine the nature of concentrated (0.5–16 m) NaCl–water mixtures under ambient (25°C, 1 bar), hydrothermal (325°C, 1 kbar) and deep crustal (625°C, 15 kbar) conditions. We used the well-established SPCE model for water together with the Smith and Dang Lennard-Jones potentials for the ions (J. Chem. Phys., 1994, 100, 3757). With increasing temperature at 1 kbar, the dielectric constant of water decreases to give extensive ion-association and the formation of polyatomic (Na(n)Cl(m))(n-m )clusters in addition to simple NaCl ion pairs. Large polyatomic (Na(n)Cl(m))(n-m )clusters resemble what would be expected in a hydrous NaCl melt in which water and NaCl were completely miscible. Although ion association decreases with pressure, temperatures of 625°C are not enough to overcome pressures of 15 kbar; consequently, there is still enhanced Na–Cl association in brines under deep crustal conditions

C–O–H–S fluids and granitic magma : how S partitions and modifies CO2 concentrations of fluid-saturated felsic melt at 200 MPa

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 162 (2011): 849-865, doi:10.1007/s00410-011-0628-1.Hydrothermal volatile-solubility and partitioning experiments were conducted with fluid-saturated haplogranitic melt, H2O, CO2, and S in an internally heated pressure vessel at 900°C and 200 MPa; three additional experiments were conducted with iron-bearing melt. The run-product glasses were analyzed by electron microprobe, FTIR, and SIMS; and they contain ≤ 0.12 wt% S, ≤ 0.097 wt.% CO2, and ≤ 6.4 wt.% H2O. Apparent values of log ƒO2 for the experiments at run conditions were computed from the [(S6+)/(S6++S2-)] ratio of the glasses, and they range from NNO-0.4 to NNO+1.4. The C-O-H-S fluid compositions at run conditions were computed by mass balance, and they contained 22-99 mol% H2O, 0-78 mol% CO2, 0-12 mol% S, and < 3 wt% alkalis. Eight S-free experiments were conducted to determine the H2O and CO2 concentrations of melt and fluid compositions and to compare them with prior experimental results for C-O-H fluid-saturated rhyolite melt, and the agreement is excellent. Sulfur partitions very strongly in favor of fluid in all experiments, and the presence of S modifies the fluid compositions, and hence, the CO2 solubilities in coexisting felsic melt. The square of the mole fraction of H2O in melt increases in a linear fashion, from 0.05-0.25, with the H2O concentration of the fluid. The mole fraction of CO2 in melt increases linearly, from 0.0003-0.0045, with the CO2 concentration of C-O-H-S fluids. Interestingly, the CO2 concentration in melts, involving relatively reduced runs (log ƒO2 ≤ NNO+0.3) that contain 2.5-7 mol% S in the fluid, decreases significantly with increasing S in the system. This response to the changing fluid composition causes the H2O and CO2 solubility curve for C-O-H-S fluid-saturated haplogranitic melts at 200 MPa to shift to values near that modeled for C-O-H fluid-saturated, S-free rhyolite melt at 150 MPa. The concentration of S in haplogranitic melt increases in a linear fashion with increasing S in C-O-H-S fluids, but these data show significant dispersion that likely reflects the strong influence of ƒO2 on S speciation in melt and fluid. Importantly, the partitioning of S between fluid and melt does not vary with the (H2O/H2O+CO2) ratio of the fluid. The fluid-melt partition coefficients for H2O, CO2, and S and the atomic (C/S) ratios of the run-product fluids are virtually identical to thermodynamic constraints on volatile partitioning and the H, S, and C contents of pre-eruptive magmatic fluids and volcanic gases for subduction-related magmatic systems thus confirming our experiments are relevant to natural eruptive systems.This research was supported in part by National Science Foundation awards EAR 0308866 and EAR-0836741 to J.D.W

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).Bio-organic Synthesi

A Functional Misexpression Screen Uncovers a Role for Enabled in Progressive Neurodegeneration

Drosophila is a well-established model to study the molecular basis of neurodegenerative diseases. We carried out a misexpression screen to identify genes involved in neurodegeneration examining locomotor behavior in young and aged flies. We hypothesized that a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the interesting candidates showing progressive arrhythmicity has reduced enabled (ena) levels. ena down-regulation gave rise to progressive vacuolization in specific regions of the adult brain. Abnormal staining of pre-synaptic markers such as cystein string protein (CSP) suggest that axonal transport could underlie the neurodegeneration observed in the mutant. Reduced ena levels correlated with increased apoptosis, which could be rescued in the presence of p35, a general Caspase inhibitor. Thus, this mutant recapitulates two important features of human neurodegenerative diseases, i.e., vulnerability of certain neuronal populations and progressive degeneration, offering a unique scenario in which to unravel the specific mechanisms in an easily tractable organism