bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of large disjoint motifs in biological networks
Authors: Elhesha Rasha , Kahveci Tamer
Published: October 2016

Background

Biological networks provide great potential to understand how cells function. Network motifs, frequent topological patterns, are key structures through which biological networks operate. Finding motifs in biological networks remains to be computationally challenging task as the size of the motif and the underlying network grow. Often, different copies of a given motif topology in a network share nodes or edges. Counting such overlapping copies introduces significant problems in motif identification.

Results

In this paper, we develop a scalable algorithm for finding network motifs. Unlike most of the existing studies, our algorithm counts independent copies of each motif topology. We introduce a set of small patterns and prove that we can construct any larger pattern by joining those patterns iteratively. By iteratively joining already identified motifs with those patterns, our algorithm avoids (i) constructing topologies which do not exist in the target network (ii) repeatedly counting the frequency of the motifs generated in subsequent iterations. Our experiments on real and synthetic networks demonstrate that our method is significantly faster and more accurate than the existing methods including SUBDUE and FSG.

Conclusions

We conclude that our method for finding network motifs is scalable and computationally feasible for large motif sizes and a broad range of networks with different sizes and densities. We proved that any motif with four or more edges can be constructed as a join of the small patterns.
A decision analysis model for KEGG pathway analysis
Authors: Du Junli , Li Manlin , Yuan Zhifa , Guo Mancai , Song Jiuzhou , Xie Xiaozhen , Chen Yulin
Published: October 2016

Background

The knowledge base-driven pathway analysis is becoming the first choice for many investigators, in that it not only can reduce the complexity of functional analysis by grouping thousands of genes into just several hundred pathways, but also can increase the explanatory power for the experiment by identifying active pathways in different conditions. However, current approaches are designed to analyze a biological system assuming that each pathway is independent of the other pathways.

Results

A decision analysis model is developed in this article that accounts for dependence among pathways in time-course experiments and multiple treatments experiments. This model introduces a decision coefficient—a designed index, to identify the most relevant pathways in a given experiment by taking into account not only the direct determination factor of each Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway itself, but also the indirect determination factors from its related pathways. Meanwhile, the direct and indirect determination factors of each pathway are employed to demonstrate the regulation mechanisms among KEGG pathways, and the sign of decision coefficient can be used to preliminarily estimate the impact direction of each KEGG pathway. The simulation study of decision analysis demonstrated the application of decision analysis model for KEGG pathway analysis.

Conclusions

A microarray dataset from bovine mammary tissue over entire lactation cycle was used to further illustrate our strategy. The results showed that the decision analysis model can provide the promising and more biologically meaningful results. Therefore, the decision analysis model is an initial attempt of optimizing pathway analysis methodology.
Ikaros 6 protects acute lymphoblastic leukemia cells against daunorubicin-induced apoptosis by activating the Akt-FoxO1 pathway
Authors: Han Juan , Jin Runming , Zhang Meiling , Guo Qing , Zhou Fen
Published: October 2016

Ikaros isoform 6 (Ik6) is associated with a poor prognosis for children with acute lymphoblastic leukemia (ALL). Our previous study demonstrated that overexpression of Ik6 enhances proliferation and chemoresistance of leukemia cells, with a possible underlying mechanism that involves antiapoptosis. In the present study, we investigated whether Ik6 protects against apoptosis by regulating the Akt-FoxO1 pathway. Bone marrow samples from children with ALL were collected and evaluated. In Ik6+ patients, the Akt-FoxO1 pathway was activated such that expression of phosphorylated Akt and FoxO1 was significantly increased, but that of Bim and p27 decreased. In vitro experiments in this study were performed by using human ALL Nalm-6 cells that were stably transfected with Ik6 (Nalm-6/Ik6) or Sup-B15 and Ik6 shRNA (Sup-B15/Ik6 shRNA). Upon treatment with daunorubicin, Nalm-6/Ik6 cells exhibited a statistically significant reduction in apoptosis, with increased expression of p-Akt and p-FoxO1. In contrast, an increase in apoptosis with decreased expression of p-Akt and p-FoxO1 was observed in Sup-B15/Ik6 shRNA cells. This protection was dependent on activation of caspase-3 cleavage. By using an activator and an inhibitor of Akt or FoxO1, we demonstrated that Akt or FoxO1 activation had no effect on Ik6 expression. In conclusion, Ik6, the upstream factor of Akt-FoxO1 pathway, can protect ALL cells against daunorubicin-induced apoptosis and can potentially be explored as a therapeutic target in the treatment of patients with ALL.
Positive PD-L1 Expression Predicts Worse Outcome in Cutaneous Angiosarcoma
Authors: Shimizu Akira , Kaira Kyoichi , Okubo Yuko , Utsumi Daisuke , Yasuda Masahito , Asao Takayuki , Nishiyama Masahiko , Takahashi Kenzo , Ishikawa Osamu
Published: October 2016

Purpose

Programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) targeted therapies have shown promising survival outcomes in several human neoplasms. However, it is unclear whether the expression of PD-L1 can be correlated to any clinical and pathologic variables in patients with cutaneous angiosarcoma (CA). The aim of this study was to evaluate the clinicopathological significance of PD-L1 expression in CA patients.

Materials and Methods

Data from 52 patients with CA were retrospectively reviewed. PD-L1 expression, tumor proliferation determined by Ki-67 index, and immunohistochemical evaluation of tumor-infiltrating lymphocytes, CD4+ and CD8+, were used to determine correlation with clinicopathological variables.

Results

PD-L1 was positively expressed in 40% of all patients. PD-L1 expression was significantly associated with tumor cell proliferation. Multivariate analysis confirmed that high levels of CD8+ tumor-infiltrating lymphocytes were a significant predictor in patients with clinical stage I CA and the positive expression of PD-L1 was an independent prognostic factor in predicting worse outcome.

Conclusion

PD-L1 expression is a novel pathologic marker for predicting worse outcome in patients with CA.
Is He Popenjoy? Deciding to Know and the Presumption of Realism
Authors: Ben-Yishai Ayelet
Published: October 2016

Presumptions—legal rules that assume a fact is true unless there is a greater weight of evidence that disproves it—mark the normal mode of things, the way things could be and most probably are. Like realist fiction, presumptions are but one of the ways in which Victorian culture addressed doubt and chose to know its reality. “Worlding” literary forms of knowing with legal/philosophical ones, through a reading of Anthony Trollope's Is He Popenjoy? (1878), I argue that realism knows by deciding to know. A focus on the presumptions—most prominently the presumption of legitimacy—that undergird Trollope's novel makes more explicit that which in his realism remains largely implicit: the complex relationship between the normative and the probabilistic that marks realism's relationship with the reality it purports to represent. After all, whatever else realism is, it is also always a historically contingent reflection of and on how we choose (knowingly or unknowingly but always communally) to know our world and make it known. Reading Is He Popenjoy? in this way allows us not only to discover surprising affinities between legal conventions and literary ones but also to understand the social and cultural work of conventionality itself, reconsidering knowing as a collective or communal endeavor. I thus suggest that the inherent commonality of epistemological structure—the way it is collectively and contingently “worlded”—offers an explanation for realism's persistence as a world phenomenon.
Simultaneous integrated boost (SIB) of the parametrium and cervix in radiotherapy for uterine cervical carcinoma: a dosimetric study using a new alternative approach
Authors: Cheng Jen-Yu , Huang Eng-Yen , Hsu Shun-Neng , Wang Chong-Jong
Published: October 2016

Objective:

To compare the dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous integrated boost (SIB) technique with that of the traditional midline block (MB) technique for boosting the parametrium in patients with cervical cancer.

Methods:

Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB) and IMRT followed by the MB technique (IMRT-MB) were generated for each of the 10 patients with cervical cancer. For the SIB plans, 45-Gy and 50-Gy dose levels in 25 equal fractions were set for the pelvis planning target volume 45 (PTV45) and the parametrial boost volume (PTV50), respectively. For the IMRT-MB plans, the parametrium was sequentially boosted with the MB technique (5.4 Gy in three fractions) after pelvic IMRT (PTV45).

Results:

Volume receiving 100% of the prescribed dose or more coverage of the PTV50 was significantly better for VMAT-SIB and IMRT-SIB than that for IMRT-MB (99.08 and 99.31% compared with 91.79%, respectively; p < 0.05). VMAT-SIB and IMRT-SIB both generated significantly greater doses to the organs at risk (OARs) except for the volume receiving 50 Gy or more doses, which were significantly lower for the bladder and bowel. Comparable results were achieved with VMAT-SIB and IMRT-SIB.

Conclusion:

The VMAT-SIB and IMRT-SIB techniques are promising in terms of dose distributions and tumour coverage, although these approaches might result in slightly higher doses of radiation to the OARs.

Advances in knowledge:

This is the first study to examine the feasibility of the SIB technique using IMRT or VMAT to boost the parametrium. The techniques dosimetrically produced better target coverage but resulted in slightly higher doses to the OARs.
Deep inspiration breath-hold radiotherapy for lung cancer: impact on image quality and registration uncertainty in cone beam CT image guidance
Authors: Josipovic Mirjana , Persson Gitte F , Bangsgaard Jens P , Specht Lena , Aznar Marianne C
Published: October 2016

Objective:

We investigated the impact of deep inspiration breath-hold (DIBH) and tumour baseline shifts on image quality and registration uncertainty in image-guided DIBH radiotherapy (RT) for locally advanced lung cancer.

Methods:

Patients treated with daily cone beam CT (CBCT)-guided free-breathing (FB) RT had an additional CBCT in DIBH at three fractions. These CBCT scans were offline rigidly registered (on tumour) to FB and DIBH CT scans acquired at planning. All registrations were repeated to evaluate the intraobserver uncertainty. CBCT scans were scored on degree of streak artefacts and visualization of tumour and anatomical structures. We examined the impact of tumour baseline shift between consecutive DIBHs on CBCT image quality.

Results:

CBCT scans from 15 patients were analysed. Intraobserver image registration uncertainty was approximately 2 mm in both FB and DIBH, except for the craniocaudal direction in FB, where it was >3 mm. On the 31st fraction, the intraobserver uncertainty increased compared with the second fraction. This increase was more pronounced in FB. Image quality scores improved in DIBH compared with FB for all parameters in all patients. Simulated tumour baseline shifts ≤2 mm did not affect the CBCT image quality considerably.

Conclusion:

DIBH CBCT improved image quality and reduced registration uncertainty in the craniocaudal direction in image-guided RT of locally advanced lung cancer. Baseline shifts ≤2 mm in DIBH during CBCT acquisition did not affect image quality.

Advances in knowledge:

DIBH RT has dosimetric advantages over FB; this work demonstrates an additional benefit of DIBH in terms of registration accuracy because of improved image quality.
The 2016 Bioinformatics Open Source Conference (BOSC)
Authors: Harris Nomi L. , Cock Peter J.A. , Chapman Brad , Fields Christopher J. , Hokamp Karsten , Lapp Hilmar , Muñoz-Torres Monica , Wiencko Heather
Published: October 2016

Message from the ISCB:

The Bioinformatics Open Source Conference (BOSC) is a yearly meeting organized by the Open Bioinformatics Foundation (OBF), a non-profit group dedicated to promoting the practice and philosophy of Open Source software development and Open Science within the biological research community. BOSC has been run since 2000 as a two-day Special Interest Group (SIG) before the annual ISMB conference. The 17th annual BOSC (http://www.open-bio.org/wiki/BOSC_2016) took place in Orlando, Florida in July 2016. As in previous years, the conference was preceded by a two-day collaborative coding event open to the bioinformatics community. The conference brought together nearly 100 bioinformatics researchers, developers and users of open source software to interact and share ideas about standards, bioinformatics software development, and open and reproducible science.
Research Roundup
Authors: Cowan Helen
Published: October 2016

Helen Cowan presents a selection of recently published articles of interest to nurses working in cardiovascular nursing. The aim of this roundup is to provide a brief overview of the research papers selected. A full reference is provided for those who wish to take a look at the research in further detail
Diagnosis and management of lipoedema in the community
Authors: Todd Marie
Published: October 2016

Lipoedema is a chronic progressive adipose disorder that affects mainly women and presents as symmetrical enlargement of the buttocks and legs. It is commonly misdiagnosed as obesity or lymphoedema, but careful assessment will reveal a disproportionate enlargement below the waist which is resistant to dieting, sparing of the feet, legs are tender or painful to touch and bruise easily, there is occasional orthostatic oedema, and there is often significant psychological morbidity. Lipoedema is a oestrogen-regulated condition with onset around puberty in 78% of women, and there is often a strong family history. The condition is exacerbated by weight gain and there is increasing anecdotal evidence that women who are obese are seeking a diagnosis of lipoedema, either to procure NHS funded manual lymphatic drainage, or to medicalise their obesity and avoid acknowledging that the responsibility for their weight gain is lifestyle orientated. Management of lipoedema consists of accurate diagnosis, psychological care, management of orthostatic oedema, and prevention of progression through skin care and weight management.
Personal reflection: A midwifery educator's revalidation experience
Authors: Clarke Elinor
Published: October 2016

Elinor Clarke is a registered midwife, who works at Coventry University as a senior lecturer in midwifery. She successfully revalidated in April 2016.

As of April 2016, midwives and nurses at all levels are required to undergo revalidation with the Nursing and Midwifery Council (NMC). The overall process is explained on the NMC website, but differs depending on the specific role of the individual. This article outlines the personal experience of a midwifery educator who revalidated this year, including tips for simplifying the revalidation process.
The NHS Heath Check screening and non-diabetic hyperglycaemia
Authors: Hudson Helen
Published: October 2016

Around 5 million people are at risk of developing type 2 diabetes in the UK. Helen Hudson analyses the role of physical activity in reducing risk, and of the general practice-based NHS Health Check in identifying people who remain undiagnosed or have modifiable risk factors

In 2015, Public Health England (PHE) predicted that 5 million people are at risk of developing diabetes in England, while Diabetes UK (2015) estimated that just under 550 000 people have undiagnosed type 2 diabetes. These figures demonstrate the importance of the role of the NHS Health Check screening programme. This article reviews the statistics, screening for non-diabetic hyperglycaemia and associated risk factors, as well as the rationale behind NHS Health Checks and their uptake, to date. It encourages practice nurses to provide advice to patients regarding the role of physical activity in reducing risk of developing type 2 diabetes.
Bariatric surgery in the treatment of morbid obesity in adolescents (literature review)
Authors: Okorokov Pavel L. , Vasyukova Olga V. , Dedov Ivan I.
Published: October 2016

Morbid obesity in children is associated with various metabolic complications, often persisting into adulthood and leading to reduced quality and duration of life. Conservative treatment of morbid obesity, often ineffective, and therefore, bariatric surgery in adolescents is becoming more common throughout the world. This review presents an analysis of international clinical guidelines for patient selection for bariatric surgery, assessed the efficiency and safety of different types of bariatric operations and identified the main problems of the widespread use of metabolic surgery as a method of treatment of morbid obesity in adolescents.
Assuring epidemiological safety for healthcare of patients with diabetes mellitus
Authors: Dedov Ivan I. , Briko Nikolay I. , Andrianova Ekaterina A. , Abramova Irina M. , Brusina Elena B. , Bunova Anna , Dementieva Larisa A. , Igonina Elena P. , Karpushkina Anna V. , Kravchuk Sergey V. , Laptev Dmitriy N. , Mayorov Alexander Y. , Panteleeva Ludmila G. , Pankratova Maria S. , Peterkova Valentina A. , Petryaykina Elena E. , Polibin Roman V. , Rybkina Irina G. , Shestopalova Tatiana N.
Published: October 2016

Healthcare associated infections (HAI) — infections that patients develop during the course of receiving healthcare in hospitals, outpatient department and at home, out of healthcare facilities, and infection resulting from occupational exposure. Patients with diabetes are vulnerable to HAI. Infections increase metabolism problems in patients with diabetes; and vice versa, high blood glucose level increases risk of infections. For assuring epidemiological safety for patients with diabetes infection control must be provided for the following medical practices: insulin injections; blood glucose test; care of diabetes foot; intravascular catheterization and surgery. Any invasive procedures increase the HAI risk. HAI are most commonly transferred through direct and indirect contact with the infection. Some of the main HIA preventive practices: staff cleaning hands with alcohol based sanitizer, single use of medical gloves, single use of insulin needles and syringes. In health facilities only multiple users and multiple blood glucose monitoring devices must be used by health providers. The protocol of glucose blood testing should include detailed disinfection procedures and additional measures to decrease the risk of potentially transmitting disease between patients and between patients and providers. Health providers should have special skills to care of patients with diabetes foot to perform non-traumatic procedures and infections control practices. Proper hand hygiene and gloves use combined with effective aseptic technique before catheter insertion and maintenance protect against severe HAI. Risk of infections significantly decreases when single-dose antibiotic was used before surgery as antimicrobial prophylaxis. To disease risk of infections patients should be recommended to strictly control diabetes during the weeks before elective surgical procedures.
Influence of novel GPR119 receptor agonist on plasma glucose and insulin level, as well as structural changes of pancreas islets in rats with experimental type 2 diabetes
Authors: Tyurenkov Ivan N. , Kurkin Denis V. , Bakulin Dmitry A. , Volotova Elena V. , Smirnov Aleksej V. , Mednikov Dmitry S. , Shafeev Mikhail A.
Published: October 2016

Background. GPR119 receptor is a promising target for novel antidiabetic drugs development because of its agonists in addition to hypoglycemic effects have cytoprotective effect on beta cells.Aim — to assess the effect of the novel GPR119 receptor agonist and sitagliptin on carbohydrate metabolism and morphological structure of the pancreas in animals with experimental type 2 diabetes.Material and methods. The study was performed in Wistar rats with streptozotocin-nicotinamide-induced diabetes. Serum insulin was determined by ELISA (Rat Insulin, (INS) ELISA Kit, 96 CSB). Immunohistochemical studies were performed using mouse monoclonal antibodies to insulin (clone 1G4, GeneTex) with determination of the absolute and relative area of immunopositive material (beta-cells) of the pancreatic islets.Results. 28-day treatment of animals with diabetes by GPR119 receptor agonist — ZB-16 (dipiaron) (1 mg/kg, per os, daily) and an inhibitor of the DPP-4 (sitagliptin) led to a reduction of fasting hyperglycemia and improve its glucose tolerance and enhance basal and stimulated insulin secretion relative to the control without treatment. Morphometric assessment of islets revealed that animals treated with the ZB-16 and sitagliptin have significantly higher absolute and relative islets area, as well as the perimeter of the insulin-positive material compared to islets of rats without treatment.Conclusion. Course administration of GPR119 receptor agonist to animals with streptozotocin-nicotinamide-induced diabetes has a pronounced antidiabetic effect consists in reducing fasting plasma glucose, improve glucose utilization, increase basal and stimulated insulin secretion, as well as increasing the area of the insulin-positive material in islets. Antidiabetic action of novel GPR119 receptor agonist, was comparable to that of sitagliptin.
Genetic markers of type 2 diabetes in Russian population
Authors: Vakhromeeva Ksenia A. , Suplotova Ludmila A. , Nosikov Valery V.
Published: October 2016

Introduction. Genetic susceptibility to Type 2 Diabetes (T2D) with a complex mode of inheritance is explained by the presence of multiple gene, each conferring a small moderate contribution the overall risk, as well as by alternative combinations of genes. Due to the success of Genome-Wide Association Study there has been rapid increase in the availability of genetic data for T2D. This allows the collection of large sets of genetic polymorphic loci, which could be key in the understanding of the genetic basis of T2D.The aim of this study was to determine alleles and allelic combinations that are associated with T2D phenotype.Methods. We assessed the associations of 96 single nucleotide polymorphisms (SNPs) linked with T2D different pathway components and carbohydrate metabolism abnormalities in 96 Russian patients and 96 normoglycemic controls using Illumina Golden Gate Genotyping Assay (low density DNA chip with 96 SNPs). T2D was defined according to the World Health Organization criteria, 1999. Data were analyzed with the free online statistical program named “Calculator for confidence intervals of odds ratio” (www.gen-exp.ru/calculator_or.php) and APSampler software (https://code.google.com/p/apsampler) for multi-locus association analysis.Results. On the first stage of the study we detected ten SNPs that can be independently contributing to T2D risk in the Russian cohort, they are rs8050136 (p=0,05) and rs11642841 (p=0,04) in FTO gene, rs2943641 (p=0,02) and rs2943634 (p=0,03) in IRS1 gene, rs571312 in MC4R gene, rs1470579 (p=0,04) in IGF2BP2 gene, rs163184(p=0,03) in KCNQ1 gene, rs11924032 (p=0,04) in SLC2A2 gene, rs11634397 (p=0,03) in ZFAND6 gene, rs7172432(p=0,04) in C2CD4A gene. On the second stage we found a biallelic combination of A allele rs8050136 in FTO gene and A allele rs7172432 in C2CD4R gene that was associated with T2D risk. Remarkable, the combined effect (association) of rs8050136 and rs7172432 was stronger (OR=1,97; p=0.006) than that of each SNP alone.Conclusion. The biallelic combination of A allele rs8050136 in FTO gene and A allele rs7172432 in C2CD4R gene can be used as a genetic marker of T2D.
Vitamin D status in infants during the first 9 months of age and its effect on growth and other biochemical markers: A Prospective Cohort Study
Authors: Gutch Manish , Kumar Sukriti , Mandal Uday Kumar
Published: October 2016

Background and aim. We planned this prospective cohort study in term newborn babies, with the objective to determine the incidence of vitamin D deficiency in infancy and to determine the level of vitamin D which triggers the physiological PTH axis of the body so as to differentiate truly deficient from sufficient vitamin D status.Methods. 96 participants at birth were enrolled and followed up till 9 months of age. Serum25OHD was estimated in cord blood at birth and at 14 ± 1 weeks of life. 77 participants were followed up at 9 months for estimation of serum 25OHD, PTH, Alkaline phosphatase (ALP), calcium and phosphorus. Vitamin D deficiency was defined as serum 25OHD <15 ng/mL as per USIOM guidelines.Results. Serum 25OHD levels at 9 months of age (15.78±8.97ng/mL) were significantly increased in comparison to the level of 3 months of age (14.04±7.10ng/mL) and at birth (8.94±2.24ng/mL).At birth all the participants (77) were deficient in 25OHD levels. It was found that 16/94 (17%)and 19/77 (24.7%) participants at 3 and 9 months of age respectively became vitamin D sufficient without any vitamin D supplementation. There was a significant inverse correlation between serum 25OHD and PTH concentration (r=-0.522, p<0.001), serum 25OHD and ALP(r=-.501, p<0.001). It was found that reduction in serum vitamin D level to below 10.25 ng/mL results in surge of serum PTH.Conclusion: Vitamin D deficiency is common from birth to 9 months of age but incidence decreases spontaneously even without supplementation. Also large number of babies may be falsely labelled as vitamin D deficient with currently followed cutoffs. So a new cutoff for vitamin D deficiency needs to be established for neonates and infants.
Effect of suppression of puberty and cross-sex hormone therapy on bone turnover markers and BMAD in transgender adolescents
Authors: Vlot Mariska Caroline , Klink Daniel T. , Den Heijer Martin , Blankenstein Marinus A. , Rotteveel Joost , Heijboer Annemieke C.
Published: October 2016

Background: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT).Objective: To investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.Methods: Thirty four female-to-males (FtMs) and 22 male-to-females (MtFs) were divided into a young and old pubertal group, based on the bone age of 14 years in the FtMs and 15 years in the MtFs. All patients received GnRHa triptorelin. CSHT was prescribed in incremental doses from the age of 16 years. FtMs received testosterone ester mixture and MtFs were treated with 17-β estradiol. BTMs P1NP, osteocalcin and ICTP and the BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. Furthermore, BMAD and Z-scores were calculated.Results: P1NP and 1CTP decreased during GnRHa treatment, indicating decreased bone turnover. Osteocalcin showed an aberrant pattern. A low BMAD Z-score of both FN and LS was observed in the MtFs at start of GnRHa treatment. The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of both FN and LS, however BMAD Z-scores of predominantly the LS decreased. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased. During CSHT BMAD Z-scores increased and returned towards normal, especially of the LS.Conclusion: Suppressing puberty by GnRHa leads to a decrease of BTMs in transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24 months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DEXA-scans remain important in follow-up of transgender adolescents.
The effect of preoperative blood glucose control on postoperative values
Authors: Amashukeli Medea Teimuraz
Published: October 2016

Background and aims. It has been largely studied and proven that tight glycemic control is necessary for the favorable outcome of coronary artery bypass graft (CABG) as it is associated with less morbidity and mortality. Insulin is considered as the fastest and safest means to control blood glucose in patients with type 2 diabetes mellitus (T2DM) in perioperative period. The aim of our study was to assess the preoperative risk factors for hyperglycemia after CABG.Materials and methods. 70 insulin-naive T2DM patients undergoing CABG were included in the study. Anthropometric, biochemical and hormonal examinations were performed before the operation. Hyperglycemia was managed with insulin. Continuous intravenous insulin infusion was used according to the Portland Protocol until the third postoperative day (target serum glucose concentration < 180 mg/dl). Patients were switched to subcutaneous insulin injections using intermediate and fast acting insulin after moving to the ward (Insulatard 100 IU/ml, Actrapid 100 IU/ml, Novo Nordisk A/S) until the day of discharge. All patients had 3-4 times daily capillary blood glucose check in the ward and mean daily glucose value was calculated.Results. The postoperative blood glucose values correlated significantly with the preoperative HbA1c values (p<0.05). The daily dose of insulin required to correct hyperglycemia correlated more with HbA1c values (p<0.005) than with patients’ weight (p<0.05).Conclusion. The preoperative good metabolic control in necessary for the patients awaiting CABG. The value of HbA1c should be considered to estimate the daily dose of insulin.
Long-term prognosis of diabetic patients with critical limb ischemia after endovascular therapy
Authors: Gorbacheva Ann M. , Abdulvapova Zera N. , Galstyan Gagik R. , Bondarenko Olga N. , Ayubova Natalya L. , Sitkin Ivan I. , Dedov Ivan I.
Published: October 2016

Introduction. Critical limb ischemia (CLI) occurs approximately 20 times more frequently among diabetic patients. Frequency of amputations is higher too. Main treatment goal in these situations is in reconstruction of arterial blood flow with bypass surgery or endovascular interventions. Nevertheless, long-term prognosis of survival, limb preservation and life quality among Russian patients that underwent this therapy remains unclear, as well as influencing risk factors.The aim of the study was to evaluate the long-term prognosis in diabetic patients with critical limb ischemia (CLI) after peripheral angioplasty with active and nonactive follow-up period.Methods. 81 diabetic patients with CLI underwent PTA in 88 limbs. Patients were divided into 2 groups: group A (n = 51) – with active follow up (FU) period (visits every 3-6 months during 5 years) and group B (n = 30) - without active FU period (the second visit in our center was performed in 5 years after PTA). Diagnosis and treatment of CLI were based on recommendation of TASC II. The primary outcome was cumulative survival, secondary outcome were cases of repeat PTA and major amputations (MA) after 5 years after surgery.Results. Only 44 (86%) patients from group A finished FU period. There were 37 (46%) men, with mean age 64,1[54-68] years, mean HbA1c 7,9±1,4%, mean duration of diabetes 16,5[0,8-43] years, diabetes type 1/2 - 8/73 (90% of type 2). 82% had arterial hypertension, 5% - strokes, 18,5% - myocardial infarction. Chronical kidney disease of stage 1-2 was detected in 55,5%, stage 3-5 – in 30,8%. Anemia was diagnosed in 67,5%, arrhythmias – in 7,4%. 49,3% of patients suffered from diabetic retinopathy. Patients from both groups were comparable in comorbidities, severity of lower limb artery obstruction’s and degree of tissue damage (p<0,05): peripheral arterial disease (PAD) 4-6 classes according Graziani classification in both groups was in 75(93%) cases; Rutherford classification in both groups: 4 category-12(15%), 5category in 43(53%), and 6 category in 29(31%) patients. Repeat PTA was performed in group A in 15 (35%), in group B in 5(16%) cases. There were major amputations in groups: A-4(9%) vs group B – 4(12%) (log-rank, p<0,05). Cumulative survival in groups: A-80%, in group B-67%. (log-rank, p<0,05).Conclusion. CLI in diabetic patients is accompanied by different complications and is characterized by severe morphological lesions of the lower limbs arteries and soft tissue lesions. Active FU period have advantages in diabetic patients with CLI after PTA: timely done reinterventions with decrease the risk of major amputations and cumulative survival.
Implementation of mobile diary app into clinical practice of gestational diabetes treatment
Authors: Pustozerov Evgenii , Popova Polina , Tkachuk Aleksandra , Bolotko Yana , Gerasimov Andrey
Published: October 2016

Introduction. The key element of successful treatment of gestational diabetes mellitus (GDM) is a well-organized diet and physical activity plan for the patient. In order to better monitor everyday life activity of patients and get more well-formed information on the process of treatment, a mobile application with electronic diary was given to patients at Almazov Federal North-West Medical Research Centre.The aim of the study is to assess the beneficial action of mHealth app diary usage in clinical practice of gestational diabetes treatment.Materials and methods. Android application diaCompanion was developed and given to a group of patients with detected GDM, who used it to keep records of food intake, blood glucose measurements, insulin injections, physical activity, sleep and ketones. These records were formed into unified electronic diaries and sent remotely to attending physicians. The developed diary app contained necessary functionality for disease management, including embedded food database with micronutrient and macronutrient parameters for more than 2000 local food items, record analysis and editing, database management, automated data retrieval and forwarding to attending physician.Results. By the end of May 2016, 85 patients were included in the study with 39 of them already ended the course. A total of 11020 measurements of blood glucose, and 11747 meals recorded by patients into the application were analyzed. The average number of recorded days per patient was 49 (a minimum of 2 and a maximum of 128 days). The average glucose levels were 4.9 + 0.7 mmol/L at fasting state, 6.3 ± 1.1 mmol/L-1 hours after breakfast, 6.2 ± 0.8 mmol/L after lunch, and 6.2 ± 0.9 mmol/L after dinner. In the analysis of food diaries the average daily energy intake was 1125 ± 405 kcal and the daily consumptions of carbs, proteins and fats were 104±42 g, 66±25 g and 60±22 g respectively. These figures are well below the recommended dietary allowance for pregnant women, may be due to underreporting by patients.Conclusion. Although the study is being in progress, the general impact of app usage revealed a high convenience of this practice from the physician’s perspective. Current approach made it possible to preserve and organize the data, which might otherwise be lost or not collected. This data may be used in medical studies, carried out on patients with GDM.
Does prostacyclin (PGI2) support porcine corpus luteum function? – data from in vitro study
Authors: Szymańska Magdalena Julia , Blitek Agnieszka
Published: October 2016

Background. Prostacyclin (PGI2) of luteal origin is involved in the control of corpus luteum (CL) development and function in cattle. PGI2 may regulate the process of angiogenesis and may stimulate progesterone (P4) secretion by luteal cells via its specific receptors, PTGIR. In contrast to cattle, the role of PGI2 in the pig CL has not yet been described.Aim. The present study aimed to investigate the effect of PGI2 on 1) P4 secretion by luteal cells, and 2) the expression of angiogenesis-related genes in endothelial cells of the porcine CL.Methods. CL collected from gilts on day 5-7 of the estrous cycle were used for enzymatic isolation of luteal (Experiment 1) and endothelial (Experiment 2) cells. In Exp. 1, cultured luteal cells were incubated with increasing (0, 0.01, 0.1, 1, 5 µM) doses of PGI2 analogues: iloprost (ILO) and carbaprostacyclin (cPGI2) for 8 h. To determine the effective doses of PGI2 analogues, P4 concentration in culture medium was examined by RIA. Thereafter, luteal cells were treated with ILO and cPGI2 at the concentration of 1 and 5 µM in the presence or absence of PTGIR antagonist (CAY10441). After 8 h of incubation the medium was collected for P4 determination. In Exp. 2, isolated endothelial cells were treated for 24 h with ILO and cPGI2 at doses of 1 and 5 µM. Then, cells were collected for analysis of Ang-1 and -2 mRNA expression using qPCR.Results. Both, ILO and cPGI2 affected P4 secretion by luteal cells. Elevated levels of P4 were observed in medium after treatment of luteal cells with 1 µM of ILO and 0.1, 1 and 5 µM of cPGI2 compared with control values (p<0.05). The addition of CAY10441 inhibited the stimulatory effect of ILO on P4 secretion, while did not change P4 production by luteal cells incubated with cPGI2. Moreover, PGI2 analogues differentially affected (p<0.05) the expression of proangiogenic factors. ILO stimulated Ang-2, whereas cPGI2 positively affected Ang-1 mRNA expression in endothelial cells at concentrations of 1 µM and 5 µM, respectively.Conclusion. PGI2 affects P4 secretion during luteal phase of the estrous cycle and may regulate the process of angiogenesis in the porcine CL.
Mir-30a and lin28b conform a double-negative feedback loop regulated by pi3k modulating thyroid cancer progression
Authors: Wert-Lamas León , Riesco-Eizaguitte Garcilaso , Gregory Richard I. , Santisteban Pilar
Published: October 2016

Background. Our recent results showed that tumor supressor miR-30a is firmly downregulated in Thyroid carcinomas. On the other hand, recent studies showed RNA- and DNA- binding proteins LIN28B and HMGA2 induce EMT, thus playing an important role in dedifferentiation and cancer malignification. Finally, latterly several authors agreed on the importance of a robust activation of PI3K for thyroid cancer emergency and progression.Aim: to study the link between the emergency of LIN28B and HMGA2, miR-30a silencing and PI3K hyperactivation, and to determine their effect on thyroid cancer progression.Methors. MiRNA targets computational predictions were performed with MiRanda algorythm. LIN28B and miR-30a expression vectors were transfected in ATC derived and normal thyroid cell lines; mRNA and protein levels were determined by qPCR, Luciferase and Western Blot. Invasion, proliferation and cell cycle assays were performed in Transwell, cell counter, and FACScan respectively.Results. MiRanda algorythm identified multiple miR30a recognition elements in all LIN28B, HMGA2 and PI3K effectors. LIN28B expression correlated with PI3K activating mutations in ATC derived cell lines. Overexpression of miR30a resulted in LIN28B, HMGA2, and several PI3K effectors silencing, and in an increase in p27(Kip) protein levels. Inversely, LIN28B overexpressing cells showed a decrease in miR30a levels and an increased expression of HMGA2 and PI3K effectors. The general outcome was a significant decrease in invasion and proliferation in miR-30a overexpressing cells and, conversely, an increase in these parameters by LIN28B.Conclusions. These data suggest the existence of a PI3K regulated feedback with a double-negative loop between miR-30a and LIN28B. Here, PI3K activation acts to switch the steady states. Initially, high miR-30a levels repress LIN28B expression. After PI3K is activated, LIN28B is produced and miR-30a is repressed. This state reinforces PI3K hyperactivation. Thus, the feedback implements a tumoral gene expression shift, contributing to thyroid cancer progression.
Use of intravenous glucocorticoids for treatment of Graves' orbitopathy
Authors: Asatiani Mariami Z.
Published: October 2016

Introduction. Graves' ophthalmopathy (GO) also known as thyroid-associated orbitopathy (TAO), is an autoimmune disorder of the retrobulbar tissue, closely linked to autoimmune thyroid disease. Less than 5-10% patients with Graves' disease will develop clinically relevant, active and progressive orbital complications. Treatment of this disease is difficult and often unsatisfactory. Glucocorticoids have been used for treatment of GO because of their anti-inflammatory and immunosuppressive actions during the active phase of GO.Case Report. In June 2013, 57 years old female patient referred to our clinic with complains of: heat intolerance, weight loss, fatigue, tachycardia, high blood pressure - classical picture of thyrotoxicosis. In 2006 subtotal resection of thyroid gland for Grave`s disease was performed. Laboratory studies revealed: TSH-0.01 (N=0.4-4.0µIU/ml); FT4-2.68 (N=0.89-1.76ng/dl); Hematology-leukocytes 4.7 (N=5.2-12.4µL); ESR-14(N=2-15); Thyroid ultrasound showed two nodules in the left lobe: 7X8X11mm, 8X8X8mm. Thyroid scintigraphy with TC-99m excluded hot and cold nodules. Anti-THS-Rec.-2.45 (N=<2.0 LU/L). The patient was given Thiamazole 30mg/day, Propranolol 10mg/day, Prednisolone 15mg/day. After six weeks of treatment the patient’s general condition was significantly improved: FT4-0.96; The dose of Thiamazole was decreased till 10mg/day, Propranolol 5mg/day, Prednisolone withheld. After 4 months the patient attended our clinic with complains of: lacrimation and duality, pain and exophthalmos of left eye. Thyroid function was within normal range. In order to exclude tumor, MRI of the head was performed- the tumor was excluded. Graves' ophthalmopathy was diagnosed. Pulse therapy was begun with Intravenous Methylprednisolone infusion according the following scheme: 1st week 1000mg once a day during 3 days, then 500 mg weekly for 3 weeks and 250 mg weekly for 3 weeks. After that the same infusion once in ten days – (total 4 infusion). Methylprednisolone 4mg 4tab. 3 times a day and Panangin 2tab. two times a day was given per-os. Glucose levels were monitored, it was always normal. After 14 weeks of pulse therapy optimized visual acuity and improvement of soft-tissue inflammatory signs and symptoms were evident.Conclusion. High-dose of i/v steroid therapy provides efficient and stable improvement in Graves' ophthalmopathy
Evaluation of potential predictors of hypopituitarism after pituitary adenoma surgery
Authors: Sampedro-Nuñez Miguel Antonio , Martin Garcia Raquel , Martin Avila Guillermo , García Centeno Rogelio , Blanco Carrera Concepción , Álvarez-Escola Cristina , Vicente Almudena , Huguet-Moreno Isabel , Ramos-Leví Ana Maria , Marazuela Monica
Published: October 2016

Introduction. Pituitary adenomas are the most frequent intracranial tumors. Surgical excision is the primary approach for these tumors, except for prolactinomas, and secondary hypopituitarism is its main complication.Aim: to assess the prevalence of postoperative hypopituitarism and analyze the risk factors involved in its development.Materials and methods. Ambispective multicenter observational study. Data were collected from The Molecular Registry of Pituitary Adenomas (REMAH). Univariate and multivariate analysis were performed in 128 patients with histologically confirmed adenomas who underwent transsphenoidal surgery between 2009 and 2015 in hospitals from Madrid, with more than one-month follow-up.Results. Postoperative hypopituitarism was found in 73.9% of cases (28.4% of new onset). Combined pituitary deficiency was the most frequently observed (46.3%), and hypoadrenalism the most frequent single postsurgical deficit (63.7%). Factors significantly associated with postoperative hypopituitarism in the univariate analysis were: previous hypopituitarism, larger tumor diameter, transsphenoidal endoscopic approach and presence of other postoperative complications (p <0.05). Independent predictors in the multivariate model were: tumor diameter and presurgical hypopituitarism for both single and multiple postsurgical deficits (p <0.05).Conclusion. Tumor size and previous hypopituitarism were independent predictors of postoperative hypopituitarism. Endoscopic transsphenoidal surgery was associated to a higher rate of hypopituitarism, and can be reconsidered as a modifiable factor in future studies.
Serum cortisol in the early post operative period after transphenoidal surgery to predict adrenal insufficiency
Authors: González Molero Inmaculada , Gonzalez Laura , Garcia Arnes Juan , Maraver Silvia , Olveira Gabriel , Arraez Miguel Angel , Tinahones Francisco
Published: October 2016

Background. Adrenal insufficiency is a common complication of transsphenoidal surgery (TSS) for pituitary adenoma. It is very important to identify patients requiring glucocorticoid replacement, minimising risks of adrenal insufficiency.Aim: to assess the performance of early ( 3ºday) post-TSS 08:00 a.m. cortisol measurement to detect and exclude secondary adrenal insufficiency.Methods. We selected patients undergoing TSS in our hospital during 12 months and performed a 3º day postoperative 08:00 a.m. cortisol measurement and cortisol+/-Synachten 6 months post-surgery. All patients received perioperative glucocorticoid replacement (First and second days postsurgery) unless basal cortisol was > 10 microg/dl and cortisol after Synachten > 23 microg/dl previous to surgery. We excluded patients with previous diagnosed and treated adrenal insuficiency. In patients with 3º day cortisol lower than 10 microg/dl we maintained glucocorticoid treatment until reevaluation with cortisol/Synachten 6 months post-surgery.In patients with 3º day cortisol higher than 10 microg/dl glucocorticoids were discontinued.Results. Data were reviewed from 20 patients (9 males, mean age 52,8 years), 18 with macroadenomas, 8 patients with cushing disease. Patients with adenomas no cushing: all patients with 3º day cortisol > 15 microg/dl had normal cortisol/Synachten 6 months post-surgery. 2 patients with 3º day cortisol between 10 and 15 microg/dl had adrenal insufficiency 6 months postsurgery.1 patient with 3º day cortisol< 10 microg/dl mantained adrenal insuficiency 6 months postsurgery. Cushing disease: all patients with 3º day cortisol > 10 microg/dl had not adrenal insuficiency 6 months postsurgery, all except one with recurrence. All patients with 3º day cortisol <10 microg/dl had not recurrences, all except one with adrenal insufficiency.Conclusion. A 3º day post-TSS cortisol > 15 microg/dl is a safe cutt off to discarge adrenal insufficiency. In cushing disease, a level < 10 microg/dl predict a low likelihood of recurrences.