bluuebunny/crossref_metadata_2025 huggingface dataset:
Descending necrotizing mediastinitis: Management and controversies
Authors: Putra Muhammad Arza , Romolo Harvey , Syafina Adinda Bunga , Sani Alvin Ariyanto , Wuryantoro  , Wardoyo Suprayitno , Susanti Dhama Shinta
Published: October 2016

Background:

Descending necrotizing mediastinitis has been known to be a life-threatening condition. It is most likely to be lethal without a prompt diagnosis and aggressive surgical management. In the surgical management of this subset of mediastinitis, a debate remains as to whether a transthoracic incision should be mandatory in addition to cervical approach.

Methods:

This is a single-center retrospective study performed at Cipto Mangunkusumo Hospital from January 2012 to June 2014. Patients with descending necrotizing mediastinitis were treated with broad-spectrum antibiotics and with cervical and transthoracic approach (via sternotomy) surgical debridement.

Results:

There were 16 consecutive cases of descending necrotizing mediastinitis. One patient did not undergo sternotomy and was ruled out from the study. The mean intensive care unit stay was 26.4 days, with a mean hospital stay of 46.7 days. There were three mortality cases reported and a total of three cases that needed reoperation. There was neither post-operative sternal dehiscence nor osteomyelitis found.

Conclusion:

Considering there are no post-operative sternal-related infection reported in this study, sternotomy should be considered as an access in descending necrotizing mediastinitis management. In the three mortality cases reported, two patients came with preoperative sepsis and one had iatrogenic subclavian artery injury.
The Significance of Ayurvedic Medicinal Plants
Authors: Kumar Syal , Dobos Gustav J. , Rampp Thomas
Published: October 2016

Traditional Indian medicine (ayurveda) is becoming increasingly popular, with many chronic conditions responding to it well. Most patients begin to take conventional medications as soon as their diagnoses are made, so ayurvedic treatments are usually undergone alongside and/or after conventional medical approaches. A detailed knowledge of the action of food, spices, and medicinal plants is needed in order to understand their potential influence fully. While societal use of ayurvedic plants and Indian spices is commonplace, without ill effect, the use of more concentrated products made from single plants, often in the form of teas or tablets, is of more concern. The mechanisms by which polyherbal drugs and their extracts act differ in many respects from the actions of single substances or synthetic drugs. Despite the fact that ayurvedic medicines are based on natural herbal materials, their safety depends on their method of administration, taking into account individuals’ needs and their specific disease conditions.
Stepfamily Relationship Quality and Stepchildren’s Depression in Adolescence and Adulthood
Authors: Jensen Todd M. , Harris Kathleen Mullan
Published: October 2016

Before reaching adulthood, one third of all youth in the United States will reside in a stepfamily household—a familial context marked by distinct challenges. Relatively few studies have explored family processes that promote youth adjustment in stepfamilies, and even fewer studies have examined these links across adolescence, emerging adulthood, and beyond. To address these gaps, we use a nationally representative sample of 758 adolescent stepchildren to examine the concurrent and long-term influence of mother–child, stepfather–child, nonresident father–child, and stepcouple relationship quality on stepchildren’s depression across three stages of development: adolescence, emerging adulthood, and young adulthood. Results from longitudinal structural equation modeling indicate that higher quality mother–child and stepfather–child relationships are directly associated with reductions in depression during adolescence and indirectly associated with reductions in depression during emerging and young adulthood via prior levels of depression; higher quality stepcouple relationships are directly associated with reductions in depression during emerging and young adulthood.
When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia
Authors: Ball Markus , List Alan F. , Padron Eric
Published: October 2016

Exome sequencing studies in chronic myelomonocytic leukemia (CMML) illustrate a mutational landscape characterized by few somatic mutations involving a subset of recurrent gene mutations in ASXL1, SRSF2, and TET2, each approaching 40% in incidence. This has led to the clinical implementation of next-generation sequencing panels that effectively identify clonal monocytosis and complement clinical prognostic scoring systems in most patients. However, most murine models based on single gene mutations fail to recapitulate the CMML phenotype, and many gene mutations are loss of function, making the identification of traditional therapeutic vulnerabilities challenging. Further, as a subtype of the myelodysplastic/myeloproliferative neoplasms, CMML has a complex clinical heterogeneity not reflected by the mutational landscape. In this review, we will discuss the discordance between mutational homogeneity and clinical complexity and highlight novel genomic and nongenomic approaches that offer insight into the underlying clinical characteristics of CMML.
Functional type Caristi-Kirk theorem on two metric spaces and applications
Authors: Chaira Karim , Marhrani ElMiloudi
Published: October 2016

In this paper, we give some generalizations of the functional type Caristi-Kirk theorem (see Functional Type Caristi-Kirk Theorems, 2005) for two mappings on metric spaces. We investigate the existence of some fixed points for two simultaneous projections to find the optimal solutions of the proximity two functions via Caristi-Kirk fixed point theorem.
Protein kinase CK2 controls T-cell polarization through dendritic cell activation in response to contact sensitizers
Authors: de Bourayne Marie , Gallais Yann , El Ali Zeina , Rousseau Philippe , Damiens Marie-Hélène , Cochet Claude , Filhol Odile , Chollet-Martin Sylvie , Pallardy Marc , Kerdine-Römer Saadia
Published: October 2016

Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin disease caused by chemicals present in the daily or professional environment. NiSO4 and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These contact sensitizers are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs; professional APCs), leading to the generation of CD8+ Tc1/Tc17 and CD4+ Th1/Th17 effector T cells. In the present study, using a peptide array approach, we identified protein kinase CK2 as a novel kinase involved in the activation of human monocyte-derived DCs (MoDCs) in response to NiSO4 and DNCB. Inhibition of CK2 activity in MoDCs led to an altered mature phenotype with lower expression of CD54, PDL-1, CD86, and CD40 in response to NiSO4 or DNCB. CK2 activity also regulated proinflammatory cytokine production, such as TNF-α, IL-1β, and IL-23 in MoDCs. Moreover, in a DC/T cell coculture model in an allogeneic setup, CK2 activity in MoDCs played a major role in Th1 polarization in response to NiSO4 and DNCB. CK2 inhibition in MoDCs led to an enhanced Th2 polarization in the absence of contact sensitizer stimulation.
Adaptive working memory strategy training in early Alzheimer's disease: Randomised controlled trial
Authors: Huntley J. D. , Hampshire A. , Bor D. , Owen A. , Howard R. J.
Published: October 2016

Background

Interventions that improve cognitive function in Alzheimer's disease are urgently required.

Aims

To assess whether a novel cognitive training paradigm based on ‘chunking’ improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).

Method

Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.

Results

Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.

Conclusions

Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.
ACAN Gene Mutations in Short Children Born SGA and Response to Growth Hormone Treatment
Authors: van der Steen Manouk , Pfundt Rolph , Maas Stephan J.W.H. , Bakker-van Waarde Willie M. , Odink Roelof J. , Hokken-Koelega Anita C.S.
Published: October 2016

Background:

Some children born small for gestational age (SGA) show advanced bone age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations have been described in children with short stature and advanced BA.

Objective:

To determine the presence of ACAN gene mutations in short SGA children with advanced BA and assess the response to GH treatment.

Methods:

BA assessment in 290 GH-treated SGA children. ACAN sequencing in 29 children with advanced BA ≥0.5 years compared with calendar age.

Results:

Four of 29 SGA children with advanced BA had an ACAN gene mutation (13.8%). Mutations were related to additional characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and broad great toes (P = 0.003). Children with one or fewer additional characteristic had no mutation. Of children with two additional characteristics, 50% had a mutation. Of children with three additional characteristics, 100% had a mutation. All GH-treated children with a mutation received gonadotropin-releasing hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than his father with the same ACAN gene mutation.

Conclusion:

This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have an ACAN gene mutation. ACAN sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems, or broad great toes. Our findings suggest that children with an ACAN gene mutation benefit from GH treatment with 2 years of GnRHa.
One Hundred Years of Egyptian Realism
Authors: Radwan Noha
Published: October 2016

The early twentieth century witnessed the birth of an Egyptian novel that was an offspring of European realism and a constituent of the project of “modernizing” the country and the region. Yet by the middle of the century, the majority of Egyptian writers were veering away from realism in search of more subjective as well as more indigenous or even hybrid narrative forms. The seventies, however, mandated another generic shift. As the impoverishing effects of global capital development and the government's neoliberal policies became preponderant, Egyptian writers reoriented their writings to address the socioeconomic conditions and search for means of resistance. I argue that this constitutes a return to realism in spite of the novels' diverse and unconventional forms. The essay ends with a comparison of two novels published at the start of the twenty-first century, one ostensibly realist, The Yacoubian Building, and one in a radically nonconventional form, An Interval for Bewilderment, and argues that other criteria besides narrative form should decide which of the two is realism and which a semblance of the genre and an obfuscation of reality.
A gene regulatory network for apical organ neurogenesis and its spatial control in sea star embryos
Authors: Cheatle Jarvela Alys M. , Yankura Kristen A. , Hinman Veronica F.
Published: October 2016

How neural stem cells generate the correct number and type of differentiated neurons in appropriate places remains an important question. Although nervous systems are diverse across phyla, in many taxa the larva forms an anterior concentration of serotonergic neurons, or apical organ. The sea star embryo initially has a pan-neurogenic ectoderm, but the genetic mechanism that directs a subset of these cells to generate serotonergic neurons in a particular location is unresolved. We show that neurogenesis in sea star larvae begins with soxc-expressing multipotent progenitors. These give rise to restricted progenitors that express lhx2/9. soxc- and lhx2/9-expressing cells can undergo both asymmetric divisions, allowing for progression towards a particular neural fate, and symmetric proliferative divisions. We show that nested concentric domains of gene expression along the anterior-posterior (AP) axis, which are observed in a great diversity of metazoans, control neurogenesis in the sea star larva by promoting particular division modes and progression towards becoming a neuron. This work explains how spatial patterning in the ectoderm controls progression of neurogenesis in addition to providing spatial cues for neuron location. Modification to the sizes of these AP territories provides a simple mechanism to explain the diversity of neuron number among apical organs.
iDamIDseq and iDEAR: an improved method and computational pipeline to profile chromatin-binding proteins
Authors: Gutierrez-Triana Jose Arturo , Mateo Juan L. , Ibberson David , Ryu Soojin , Wittbrodt Joachim
Published: October 2016

DNA adenine methyltransferase identification (DamID) has emerged as an alternative method to profile protein-DNA interactions; however, critical issues limit its widespread applicability. Here, we present iDamIDseq, a protocol that improves specificity and sensitivity by inverting the steps DpnI-DpnII and adding steps that involve a phosphatase and exonuclease. To determine genome-wide protein-DNA interactions efficiently, we present the analysis tool iDEAR (iDamIDseq Enrichment Analysis with R). The combination of DamID and iDEAR permits the establishment of consistent profiles for transcription factors, even in transient assays, as we exemplify using the small teleost medaka (Oryzias latipes). We report that the bacterial Dam-coding sequence induces aberrant splicing when it is used with different promoters to drive tissue-specific expression. Here, we present an optimization of the sequence to avoid this problem. This and our other improvements will allow researchers to use DamID effectively in any organism, in a general or targeted manner.
The GDNF-GFRα1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM
Authors: Irala Dolores , Bonafina Antonela , Fontanet Paula Aldana , Alsina Fernando Cruz , Paratcha Gustavo , Ledda Fernanda
Published: October 2016

The formation of synaptic connections during nervous system development requires the precise control of dendrite growth and synapse formation. Although glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 are expressed in the forebrain, the role of this system in the hippocampus remains unclear. Here, we investigated the consequences of GFRα1 deficiency for the development of hippocampal connections. Analysis of conditional Gfra1 knockout mice shows a reduction in dendritic length and complexity, as well as a decrease in postsynaptic density specializations and in the synaptic localization of postsynaptic proteins in hippocampal neurons. Gain- and loss-of-function assays demonstrate that the GDNF-GFRα1 complex promotes dendritic growth and postsynaptic differentiation in cultured hippocampal neurons. Finally, in vitro assays revealed that GDNF-GFRα1-induced dendrite growth and spine formation are mediated by NCAM signaling. Taken together, our results indicate that the GDNF-GFRα1 complex is essential for proper hippocampal circuit development.
Antagonism between β-catenin and Gata.a sequentially segregates the germ layers of ascidian embryos
Authors: Imai Kaoru S. , Hudson Clare , Oda-Ishii Izumi , Yasuo Hitoyoshi , Satou Yutaka
Published: October 2016

Many animal embryos use nuclear β-catenin (nβ-catenin) during the segregation of endomesoderm (or endoderm) from ectoderm. This mechanism is thus likely to be evolutionarily ancient. In the ascidian embryo, nβ-catenin reiteratively drives binary fate decisions between ectoderm and endomesoderm at the 16-cell stage, and then between endoderm and margin (mesoderm and caudal neural) at the 32-cell stage. At the 16-cell stage, nβ-catenin activates endomesoderm genes in the vegetal hemisphere. At the same time, nβ-catenin suppresses the DNA-binding activity of a maternal transcription factor, Gata.a, through a physical interaction, and Gata.a thereby activates its target genes only in the ectodermal lineage. In the present study, we found that this antagonism between nβ-catenin and Gata.a also operates during the binary fate switch at the 32-cell stage. Namely, in marginal cells where nβ-catenin is absent, Gata.a directly activates its target, Zic-r.b (ZicL), to specify the marginal cell lineages. Thus, the antagonistic action between nβ-catenin and Gata.a is involved in two consecutive stages of germ layer segregation in ascidian embryos.
A randomized control trial evaluating fluorescent ink versus dark ink tattoos for breast radiotherapy
Authors: Landeg Steven J , Kirby Anna M , Lee Steven F , Bartlett Freddie , Titmarsh Kumud , Donovan Ellen , Griffin Clare L , Gothard Lone , Locke Imogen , McNair Helen A
Published: October 2016

Objective:

The purpose of this UK study was to evaluate interfraction reproducibility and body image score when using ultraviolet (UV) tattoos (not visible in ambient lighting) for external references during breast/chest wall radiotherapy and compare with conventional dark ink.

Methods:

In this non-blinded, single-centre, parallel group, randomized control trial, patients were allocated to receive either conventional dark ink or UV ink tattoos using computer-generated random blocks. Participant assignment was not masked. Systematic (∑) and random (σ) setup errors were determined using electronic portal images. Body image questionnaires were completed at pre-treatment, 1 month and 6 months to determine the impact of tattoo type on body image. The primary end point was to determine that UV tattoo random error (σ  setup) was no less accurate than with conventional dark ink tattoos, i.e. <2.8 mm.

Results:

46 patients were randomized to receive conventional dark or UV ink tattoos. 45 patients completed treatment (UV: n = 23, dark: n = 22). σ  setup for the UV tattoo group was <2.8 mm in the u and v directions (p = 0.001 and p = 0.009, respectively). A larger proportion of patients reported improvement in body image score in the UV tattoo group compared with the dark ink group at 1 month [56% (13/23) vs 14% (3/22), respectively] and 6 months [52% (11/21) vs 38% (8/21), respectively].

Conclusion:

UV tattoos were associated with interfraction setup reproducibility comparable with conventional dark ink. Patients reported a more favourable change in body image score up to 6 months following treatment.

Advances in knowledge:

This study is the first to evaluate UV tattoo external references in a randomized control trial.
Recent advances in understanding hepatic drug transport
Authors: Stieger Bruno , Hagenbuch Bruno
Published: October 2016

Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo.
Key Reasons Why Transformation Projects Fail: Case-Study of a Procurement Function Transformation Project in a Large Russian Energy Corporation
Authors: �������  , Knyazeva Arina
Published: October 2016

Challenging issue of transformation project (program) management is discussed

in this paper. Transformation projects are widely implemented by

companies and their successful implementation has a direct impact on the

competitiveness of companies. There are a number of transformation project

management methodologies invented and widely implemented today,

however, according to various estimates, from 60 to 70% of the transformation

projects still fail.

This article describes main transformation project management methodologies,

as well as the results of various researches done in the field of identification

of factors of failure of transformation projects. This paper explores an

unsuccessfully implemented transformation project of procurement function

in a large Russian energy corporation. Key failure factors of transformation

project implementation are revealed and recommendations to prevent the

issues identified are made in the form of �lessons learnt�.
Exploring the Influence of Project Management System on Success of Company�s Projects Implementation
Authors: ��������  , Baranova Lidiya
Published: October 2016

The purpose of the paper is to research the influence of project management system on success of company�s projects implementation. The paper presents a review of the scientific literature on the approaches and methods in the IT project management. The components of IT project management system are presented along with the key projects success factors. There were identified and quantitatively analyzed the relationship between the project management system components and success factors of projects. According to the results of the research conducted, the change management system and the communications are the most critical factors influencing IT projects success.
A Bayesian Methodology for Systemic Risk Assessment in Financial Networks
Authors: Gandy Axel , Veraart Luitgard A. M.
Published: October 2016

We develop a Bayesian methodology for systemic risk assessment in financial networks such as the interbank market. Nodes represent participants in the network, and weighted directed edges represent liabilities. Often, for every participant, only the total liabilities and total assets within this network are observable. However, systemic risk assessment needs the individual liabilities. We propose a model for the individual liabilities, which, following a Bayesian approach, we then condition on the observed total liabilities and assets and, potentially, on certain observed individual liabilities. We construct a Gibbs sampler to generate samples from this conditional distribution. These samples can be used in stress testing, giving probabilities for the outcomes of interest. As one application we derive default probabilities of individual banks and discuss their sensitivity with respect to prior information included to model the network. An R package implementing the methodology is provided.

This paper was accepted by Noah Gans, stochastic models and simulation.
Experimental Archaeology at the University of Bologna, widening and opening archaeological research
Authors: Maurizio Cattani
Published: October 2016

The establishment of an Experimental Archaeology Laboratory at the University of Bologna has created the opportunity to offer students new training methods and to take on scientific research dedicated to the analysis and comprehension of ancient technologies. The Laboratory is based on the participation of several specialists, including archaeologists, technicians, ethno-archaeologists, and experts in archeometry, with the shared aim of investigating, documenting and understanding the past. Using limited financial resources, initial activities took place near the Bronze Age settlement of Solarolo, where the synergy among local institutions, land owners, academics and the general public created a basis on which to prepare activities and zones dedicated to different aspects of experimental archaeology.
Human remains in archaeology. Excavation, recording and analysis of data: the funerary context of San Severo in Classe
Authors: Debora Ferreri
Published: October 2016

Funerary archaeology reveals burial practices and the ways in which such mortuary practices can express social identities. The integration of archaeological and anthropological evidence can offer significant data regarding burials. The study of the cemeteries of San Severo at Classe (Ravernna) is being carried out using this integrated approach. All phases of the site of San Severo are characterised by burials and this funerary practice changed and developed, reflecting the life of the basilica and the monastery. All information regarding the characteristics of the layers, the phases and activities of members is entered in the GIS platform, so composite plans can be automatically generated.
Sequelae of large-head metal-on-metal hip arthroplasties
Authors: van Lingen Christiaan P. , Zagra Luigi M. , Ettema Harmen B. , Verheyen Cees C.
Published: October 2016

Large-head metal-on-metal (MoM) bearings were re-popularised in the late 1990s with the introduction of modern hip resurfacing (HR), followed closely by large metal head total hip arthroplasty (THA). A worldwide increase in the use of MoM hip arthroplasty subsequently saw a sharp decline, due to serious complications. MoM was rapidly adopted in the early 2000s until medical device alerts were issued by government regulatory agencies and national and international organisations, leading to post-marketing surveillance and discontinuation of these implants. Guidelines for MoM hip implant follow-up differ considerably between regulatory authorities worldwide; this can in part be attributed to missing or conflicting evidence. The authors consider that the use of large-head MoM THA should be discontinued. MoM HR should be approached with caution and, when considered, should be used only in patients who meet all of the recommended selection criteria, which limits its indications considerably. The phased introduction of new prostheses should be mandatory in future. Close monitoring of outcomes and long-term follow-up is also necessary for the introduction of new prostheses.

Cite this article: van Lingen CP, Zagra LM, Ettema HB, Verheyen CC. Sequelae of large-head metal-on-metal hip arthroplasties: current status and future prospects. EFORT Open Rev 2016;1:345-353. DOI: 10.1302/2058-5241.1.160014.
Hereditary variant of diabetes mellitus caused by a defect of the NEUROD1 gene (MODY6): the first description in Russia
Authors: Gioeva Olesya A. , Kolodkina Anna A. , Vasilyev Evgeny V. , Petrov Vasiliy M. , Tiulpakov Anatoly N.
Published: October 2016

MODY (Maturity-Onset diabetes of the young) is a heterogeneous group of disorders characterized by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic b-cells. Currently 13 candidate genes of MODY, and, respectively, 13 MODY subtypes are known. The final diagnosis can be established only on the basis of molecular genetic studies, which is the «gold standard» in the diagnosis of this disease. MODY2 and MODY3 are the most prevalent subtypes and were previously described in our country. Rare MODY subtypes have not been described in Russian literature. In this article we describe the first diagnosed case of MODY6 in Russia (a defect of the NEUROD1 gene, encoding neurogenic differentiation factor 1, which plays an important role in normal differentiation of β-cells of the pancreas and the regulation of transcription of the insulin gene). Molecular genetic study was conducted using the method of next-generation sequencing, has recently been widely used for genetic verification of monogenic diseases and, in particular, MODY. Technology of next-generation sequencing for diagnosing inherited disorders of carbohydrate metabolism in domestic practice used for the first time.
ACTH-producing medullary thyroid cancer. Clinical case.
Authors: Marova Evgenia I. , Rozhinskaya Ludmila Ya. , Voronkova Iya A. , Remizov Oleg V. , Zavalishina Anna I. , Slashchuk Konstantin Yu. , Davydov Mihail I. , Brzhezovsky Vitaliy Zh. , Gerasimov Sergey A. , Chekini Antonio K. , Stelmach Dmitry K. , Pak Maksim B.
Published: October 2016

Medullary thyroid cancer with ectopic ACTH production - the disease is extremely rare. The literature describes only a few cases of this disease. Rare ectopic ACTH syndrome caused by medullary thyroid cancer, and the diversity of the clinical picture are responsible for numerous diagnostic errors leading to ineffective treatment. In this regard, we consider it expedient to share our own experience in this area.
An analysis of the association between a polymorphism rs5219 of KCNJ11 and GFR in CKD development in patients with type 2 diabetes in Russian population
Authors: Zheleznyakova Anna V. , Vikulova Olga K. , Savelyeva Svetlana A. , Nosikov Valeriy V. , Shestakova Marina V.
Published: October 2016

Background. Chronic kidney disease is one of the most serious diabetic complications, which end-stage leads to a dramatic decline of renal function and needs for renal replacement therapy. Due to the progressive nature of CKD and the limited efficacy of treatment for advanced stages the prediction of risks and diagnostics on preclinical stage are of great importance. All of the above determines the high relevance of search for genetic markers predict the chronic kidney disease (CKD) development.The aim of our study was to investigate association between polymorphic marker (PM) of gene involved in insulin secretion with development of CKD in type 2 diabetic (T2D) patients. Polymorphism of KCNJ11 gene is associated with different phenotypes of glycemic disorders: neonatal diabetes, hyperinsulinemia, reduced insulin secretion and increased risk of type 2 diabetes. This gene coding Kir6.2 subunit of ATP-dependent potassium channels. The pathogenesis of it’s involvement in renal damage development referred to the fact that this type of potassium channels found not only in the beta- cells, but also in smooth muscle cells of blood vessels, and therefore might have an effect on risk of vascular complications, including CKD.Materials and methods. We enrolled 444 T2D patients. PM rs5219 in KCNJ11 gene was analysed among patients divided in 2 groups: with and without CKD (n=123/321) based on glomerular filtration rate (GFR) < and ≥ 60 ml/min/1,73m2 calculated by MDRD formula. PM studied using PCR. Differences in alleles/genotypes frequencies were assessed by χ² and odds ratio (OR) were calculated. The study was approved by local ethical committee; informed concern was obtained from all the patients.Results. We studied the main clinical parameters: age, HbA1c, serum levels of cholesterol and triglycerides, BP between the groups. We observed significant differences in alleles/genotypes distribution of rs5219 in KCNJ11 gene between groups with and without CKD: the prevalence of allele C and genotype CC in patients without CKD: OR=0,53, 95%CI: 0,40-0,72 and OR=0,46, 95%CI: 0,27-0,79, respectively; while allele T and genotype TT did as risk factors: χ²=17,33; р=0,0002; OR=1,87, 95%CI: 1,39-2,53; genotype TT OR=2,39, 95%CI: 1,52-3,76.Conclusions. We conclude that T2D patients might have genetic susceptibility to CKD development caused by polymorphism rs5219 of KCNJ11 gene with protective role of allele C and genotype CC and risk allelе/genotype is T/TT.
The effect of vitamin D deficiency on the severity and course of manifestation in type 1 diabetes mellitus in children
Authors: Aghajanova Elena Mikhail , Hakobyan Sergey Harutyun , Hakobyan Sona Vahagn , Zohrabyan Naira Hrachya
Published: October 2016

Background. As a hormone, vitamin D is involved in a number of processes (normal brain formation, anticancer effect, cardioprotection effect, immune defense, etc.). In diabetes mellitus type 1 several genetic and epidemiologic factors have been recognized. There is some epidemiologic evidence that decreased vitamin D level in pregnancy or early childhood may be associated with diabetes risk, but the evidence is not yet conclusive. Low level of vitamin D has also been shown to have negative effect in beta-cells function. In our work the influence of vitamin D deficiency on the gravity of manifestation of type 1 diabetes in children was estimated.Aim. To discover vitamin D deficiency and its effect on glycemic control in newly diagnosed type 1 diabetic children in Armenia.Methods. Newly diagnosed type 1 diabetic children were investigated (n=74). In all children the level of vitamin D and glycohemoglobin on the 4th day of diagnosis were evaluated. Vitamin D normal range lies between 13-67ng/L.Results. There were 51,35% (n=38) boys and 48,65% (n=36) girls by sex distribution. Distribution by age groups was as following : 0-4 years, n=14, 5-9 years, n=23, 10-14 years, n=32 and 15-17 years, n=5. Vitamin D deficiency was found in 58,11% patients (n=43). By age groups vitamin D deficiency was as following: 0-4 years - 78,55% (n=9), 5-9 years - 47,83% (n=11), 10-14 years - 62,5% (n=20), 15-17 years -60% (n=3). In 78,38% of cases (n=58) there was ketoacidosis on admission, and in 21,62% (n=16) -only ketosis. Moreover, vitamin D deficiency predominantly was met in the group of ketoacidosis cases (n=39, 67,24%), and in the ketosis group deficiency was seen only in 4 patients (25%). Average HbA1c was almost the same in the group of vitamin D deficiency and without (9,68% and 9,36%respectively).Conclusion. Positive correlation between severity of manifestation of disease and vitamin D deficiency have been revealed, and probably vitamin D deficiency has an impact on the further course of diabetes. Therefore it can be suggested to see the level of 25 OH vit D in all cases of newly diagnosed DMT1, and include the management of vit D deficiency in the protocol of DMT1 treatment.
Switching from insulin to oral sulfonylureas in patients with permanent neonatal diabetes – case report
Authors: Herescu Irina Elena , Mintici Luana , Purcaru Mircea , Ioacara Sorin , Fica Simona
Published: October 2016

Introduction. Neonatal diabetes is a rare disease and it is frequently caused by a mutation in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel. If the neonatal diabetes is associated with epilepsy and developmental delay, then the diagnosis is of DEND syndrome (developmental delay, epilepsy and neonatal diabetes).Aim. To determine which are the best methods of diagnosis and treatment for a child with neonatal diabetes.Methods and results. We present the case of a 9 years old girl, diagnosed with neonatal diabetes at age 3 months, who was first admitted to our clinic in December 2015 for frequent episodes of hyperglycemia at home and absence seizure lasting 2-4 minutes, suggesting minor epilepsy. The patient was treated with insulin from the moment of diagnosis until age 9 months, then with oral antidiabetic agents until January 2015, when she started again the insulin therapy in the context of persistent hyperglycemia and a level of glycated hemoglobin (HbA1c) of 10.6%. Her physical examination revealed height and weight according to age, with stable vital signs. The laboratory findings were all unremarkable, except for blood glucose values of 200-300 mg/dl and HbA1c level of 10.3%. The patient also had moderate mental delay, with an IQ of 66. The genetic testing for neonatal diabetes revealed a heterozygous mutation in KCNJ11 gene, so the diagnosis was of DEND syndrome. We initiated the treatment with glibenclamide 3.5 mg, 8 tablets/day and we recommended cognitive functions’ stimulation with exercises and reading 4-5 hours/day.Conclusions. The genetic testing for the identification of a mutation in KCNJ11 gene has an important impact on the therapeutic approach in children with neonatal diabetes, as there is the possibility to replace the insulin therapy with antidiabetic oral agents, therefore improving the quality of life and possibly the epilepsy seizures.
Clinical course of gestational diabetes mellitus (GDM) and pregnancy outcomes in women with GDM in relation to the method and term of diagnostic
Authors: Bunak Irina , Dreval' Aleksandr , Shestakova Tat'jana
Published: October 2016

Background and aims. Due to changes in criteria of diagnosis of GDM in Russia from 2013, it is relevant to study clinical course of GDM and pregnancy outcomes depending on terms and methods of diagnosis of GDM.Material and methods. 192 pregnant women aged 29,4±5,5ys, with a body weight 68,8±14,8 kg, BMI 25,3±5,3. 1st group: 86 pregnant women with high fasting glucose level before 20th week of pregnancy, 2nd group: 43 pregnant women with hyperglycemia in OGTT after 20th week of pregnancy, 3rd group: 63 pregnant women without GDM - control group.Results. Pregnant women with GDM were older than non-GDM women (29,5±5,4ys., 30,8±5,3ys., 28,4±5,7ys, р=0,05) and had higher body weight (72,3±16,9 kg, 68,0±12,4 kg, 64,4±11,5 kg, р=0,016). There weren't difference in age, BMI between groups 1st and 2nd. The proportion of compliant women was the same in groups 1st and 2nd (38,4% and 34,9%, p=0,85). Pregnant women who needed insulin were older and had higher BMI (32,4 ± 5,3 ys. vs. 28,9 ± 5,4 ys, р=0,04; 29,7 ± 7,1vs.25,6 ± 5,7, р=0,03 respectively). The number of women treated by insulin was higher in 2nd group (46,6%vs.15,5%, p=0,03). Women, who treated by insulin, were younger and had higher BMI in 1st group compared with 2nd group (29, 0±4,7ys vs 35,0±4,3ys, р=0,03; 34,4±5,7 vs 26,1±5,9 respectively, р=0,02). There was a significant difference in delivery term and summary severe adverse outcomes (macrosomia, preterm delivery, stillbirth) between non-compliant women with GDM and 3rd group (38,6±2,7ws 1st group, 38,0±1,9ws 2nd group, 39,5±1,09ws 3rd group, р=0,008; 34,3% 1st group, 66,7% 2nd group, 19,4% 3rd group, р=0,027). The frequency of macrosomia and summary adverse pragnancy outcomes (hypoglicemia, neonatal jaundice, clavicle fracture, asphyxia) was higher in non-compliant women with GDM compared with compliant women ((29,5% vs. 12,2%, р=0,03; 70,5% vs. 46,3%, р=0,02 respectively).Conclusions: Pregnant women with GDM diagnosed on base of high fasting glucose level, need insulin less frequently. Pregnancy outcomes in women with GDM depend on compliance rather than on terms or methods of diagnosis.
Pregnancy and delivery associated with Cushing’s disease
Authors: Grigoryants Sofya A. , Belaya Zhanna E. , Melnichenko Galina A. , Dzeranova Larisa K. , Pigarova Ekaterina A. , Ponomareva Tatyana A
Published: October 2016

Aim. We evaluated retrospective cohort data from 22 patients whose pregnancy associated with proven Cushing’s Disease (CD) in order to estimate its consequences for mother and child.Methods. The data was collected from individual patients referred to our department and from the personal contact with patients whose data was available through the Russian database. All subjects had medical records sufficient to confirm CD. Results. The following complications during pregnancy were suggested to be more common: arterial hypertension (45%), uterus hypertonus (41%), miscarriage risk (36%), late preeclampsia (18%), gestational diabetes (14%), fetal hypoxia (14%), placental detachment (10%). The common complications during delivery were entanglement umbilical cord of the fetus (n=9 ), fetal hypoxia (n= 8), bleeding (n=6 ), arterial hypertension (n= 4),CNS depression syndrome (n= 4).Women whose CD was manifested during or after the pregnancy had less complications as compared to women who had CD before pregnancy. The newly diagnosed during pregnancy or just after pregnancy patients with CD were more likely to achieve remission after the postpartum neurosurgery (100% of remission), as compared to women who suffered from CD before pregnancy (69% of remission). Moreover, the exacerbation of CD was registred after delivery (in 18 out of 22 subjects) and 50% (in 4 out of 8 subjects) recurrence rate in patients who were in remission before pregnancy. The age of children (n=22 ) varied from 1 to 10 years, and 70% were practically healthy at the moment of examination. However, some children suffered from headache ( 27% or n = 6), dizziness (27% or n = 6) or expansion pyelocaliceal system (14% or n=3). The identified data seems to be not differed from the population. According to Russian database, 33% of children were born with health problems in 2014. Conclusions. The complication rate in pregnancy rises with the activity of CD, but up to 70% of newborns are healthy and the existing health problems seems to be not specific. Up to 50% of patients with the history of CD might had the recurrences of the disease after the delivery. Consequently, pregnancy in CD should be prolonged, but careful examination must be recommended to all women with the history of CD after delivery.
mRNA analysis of genes responsible for idiopathic hypogonadotrophic hypogonadism
Authors: Loktionova Anna S. , Eneva Natela G , Khusniyarova Karina A. , Nefedova Lidia N , Kim Alexander I. , Dreval Alexander V. , Ilovayskaya Irena A.
Published: October 2016

Background. Hypogonadotropic hypogonadism (HH) is a disorder characterized by delayed or absent pubertal development due to pathology of the hypothalamic-pituitary-gonadal axis. HH may be both congenital (Kallmann’s syndrome) and sporadic. Congenital or isolated HH is divided into with anosmia/hyposmia (KS) and with normal olfaction (nIHH). Nowadays several tens of genes involved in the functioning of the reproductive axis are known. However DNA lesions can be found just in 5-15% of such cases of HH.Aim. So we decided to measure mRNA expression of several genes which can be found in leukocytes of peripheral blood - namely GNRHR and GNRH1 (are necessary for adequate biological effect of GnRH); PROK2 and CHD7 (are responsible for the migration of GnRH neurons), WDR11 and DUSP6 (are involved in normal sexual development).Methods. A quantitative determination of mRNA expression of these genes were comlpeted in the fresh peripheral blood sample by PCR in real time.Results. Examined patients: 9 women with hypogonadotropic hypogonadism (age from 18 to 28 y.o.); duration of the disease from 2 to 15 years; 3 of them – amenorrhea I and 6 – amenorrhea II. Reasons of amenorrhea II were: stress, excessive exercises, rapid body weight loss, past use of oral contraceptives. The control group: 19 healthy women; age from 19 to 37 y.o.; with regular ovalutory menstrual cycle, some of them have children. mRNA expression of examined genes differed from normal patterns in each case of hypogonadotropic hypogonadism. Changes in GNRHR, GNRH1 and DUSP6 mRNA expression were found in most of cases. However variations of mRNA expression were multidirectional in each case and there was no similarity among expression profiles of patients according to amenorrhea type or anamnestic factors.Conclusions. According to our preliminary results, in women with hypogonadotropic hypogonadism the functional activity damage of “reproductive-responsible” genes could be found in each case. Probably mRNA expression measuring could be a perspective method for proving hypothalamo-pituitary level of reproductive disorders and may help to determine which genes should be tested for DNA impairment.
Impact of weight loss on the cardiovascular system after bariatric surgery
Authors: Leca Bianca Maria , Stanca Ionuț , Florea Suzana , Fica Simona , Sîrbu Anca Elena
Published: October 2016

Introduction. Obesity is a chronic disease with a great impact on the cardiovascular system through its association with type II diabetes, hypertension, dyslipidemia, metabolic syndrome (MetS) and also through direct alterations in cardiac performance and morphology. Recent long term studies prove that substantial weight loss obtained via bariatric surgery is capable of improving cardiac risk factors associated with severe obesity, decreasing the mortality rates.Aim: to assess the long-term changes in cardiovascular risk and cardiac structure in obese patients who had lost weight after laparoscopic sleeve gastrectomy (LSG).Methods. Fifty-two severe obese patients (44±9 years, 57.7% women, BMI=45±8 kg/m2) underwent clinical and biochemical examination and Doppler echocardiograms before and 5 years after LSG.Results. Pre-operatively, 78.4% of patients were hypertensive, 46.2% had diabetes, 73.1% MetS and 44.2% presented left ventricle hypertrophy (LVH), reflecting high cardio-metabolic risk. The patients reassessment was made 61.7±10.5 months after LSG, when a decrease in BMI of 21.9±10% was achieved (p<0.001). The prevalence of hypertension (64.7%), diabetes (32.7%) and MetS (28.8%) decreased compared to the pre-operative examination (p=0.019, p<0.001, p=0.036). An increase in left ventricle mass and left ventricle mass index (LVMI) (p<0.001) and in the prevalence of LVH (57.7%-p=0.001) was recorded. Patients were divided into two groups based on the decrease in LVMI (positive response-38.5%) or increase in LVMI post-surgery (negative response-61.5%), compared with pre-operative values. The group of patients with negative response had lost less weight (p=0.006), had a poor glycemic control (p=0.022), and higher systolic (p=0.004) and diastolic (p=0.030) pressure values compared to the first evaluation.Conclusion. The increase of LVMI after LSG indicates that this study should continue, including a larger number of patients. It is important to identify the factors that can predict an inappropriate response to surgery, in order to prevent and treat them.