Репозиторий Университета

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2018 by the authors. The aim of the study was to investigate the effects of several decalcifying agents used as irrigant solutions in endodontic treatment on collagen and mineral components of dentin. Coronal dentin discs from five caries-free human third molars with a smear layer were treated for one minute with a chelating solution (1% Ethylenediaminetetraacetic acid (EDTA), 10% EDTA, 17% EDTA, 10% citric acid). Mineralization degree (Ca/N and P/N atomic ratios, IR Iapatite/Iamide II and I1410(carbonate)/I554(phosphate) spectroscopic ratios) and possible collagen rearrangements (collagen infrared (IR) amide II e III shifts) were evaluated by environmental scanning electron microscopy (ESEM)/energy dispersive X-ray spectroscopy (EDX) and IR spectroscopy before and after treatment (T0) and after ageing (T24h and T2m) in simulated body fluid (SBF). At T0, analysis showed that the highest demineralizing effect was achieved using a 10% citric acid solution and 10% EDTA, while the smallest effect was observed when using 17% EDTA. No significant collagen modifications were detected upon treatment with 1% EDTA, while subtle changes were observed after the other treatments. At T24h or T2m, analyses showed the highest remineralization values for 1% EDTA and the lowest for 10% citric acid, mainly at T2m. The samples treated with 17% EDTA showed slight collagen rearrangements upon remineralization. In conclusion, the highest demineralizing effect was observed for 10% EDTA and 10% citric acid. Collagen rearrangement was found for all the treatments except for 1% EDTA. The highest remineralization capability in SBF values was recorded for 1% EDTA and the lowest for 10% citric acid. A slight collagen rearrangement upon remineralization was still present in 17% EDTA-treated samples. Clinical use as a chelating agent in the endodontic therapy of citric acid and concentrated EDTA solutions should be reconsidered.

© 2019, The Author(s). Background: In recent years, joint replacement surgery has gradually progressed towards the fast-track model, and early rehabilitation immediately after surgery is regarded fundamental for optimal recovery of function: the aim of the present study is to describe the efficacy in perioperative management of pain in patients undergoing total hip replacement surgery and treated with tapentadol or oxycodone/naloxone in combination with ketoprofene. Methods: Single-center retrospective study on patients with moderate-severe pain, referred to total hip replacement. Patients received either tapentadol (100 mg/twice-daily post-surgery – treatment group) or oxycodone/naloxone (10 mg/5 mg post-surgery – control group) plus ketoprofen 100 mg/ twice daily. Supplemental analgesia (paracetamol 1 g or morphine 0,1 mg/kg sc) was provided if needed. Pain at rest and pain during movement were evaluated on a daily basis for 4 days post-op, after which patients were usually discharged. All adverse events were reported and compared between the two groups. Results: 106 patients were analyzed in the tapentadol group and compared to 105 patients treated with oxycodone/naloxone. Both pain intensity at rest and upon movement were significantly lower in the tapentadol group at all follow-up times (p < 0.001). Throughout T1-T4, supplemental analgesia was needed by significantly less tapentadol patients compared to the control group. Similarly, regarding side effects, a significantly higher occurrence of post-op nausea, vomit, itching and constipation was observed in the control group (p < 0.001 in all cases). Conclusion: Results from the present study support the use of tapentadol in combination with ketoprofen for the management of moderate-severe pain in the setting of major orthopedic surgery, given its effectiveness in reducing pain intensity, and its satisfactory tolerance.

© 2019 Wiley Periodicals, Inc. Background: Despite advances in treatment, the recurrence rates for laryngeal cancer range from 16% to 40%. Methods: Patients with recurrent laryngeal cancer treated at Memorial Sloan Kettering (MSK) from 1999 to 2016 were reviewed. Survival outcomes were analyzed. Results: Of 241 patients, 88% were male; the median age was 67 years; 71% had primary glottic tumors. At initial treatment, 72% of patients were seen with early stage disease; primary treatment was radiation (68%), chemoradiation (29%), and surgery (3%). The most common salvage surgery was total laryngectomy (74%). Forty-seven percentage were upstaged at salvage surgery. The 2- and 5-year disease-specific survival (DSS) was 74% and 57%, respectively. Patients with cT4 disease treated with nonsurgical primary management had a 0% 5-year DSS. Independent predictors of DSS were tumor location, perineural invasion, margin, and stage. Conclusions: Salvage surgery results in acceptable oncologic outcomes. Stage, disease site, perineural invasion, and margins are associated with inferior DSS.

© 2019 The Authors Introduction: Abdominal abscesses are one of the frequent and dangerous postoperative complication. They occur as a result of failure of seams esophagojejunal anastomosis after gastrectomy (17%), perforation of gastric and duodenal ulcers (26.8%), splenectomy (25.4%), failure of biliodigestive anastomoses (23.8%), inadequate drainage of the subphrenic space (22.2%), acute pancreatitis (14%). Left-sided subphrenic abscesses are the most common of them. Case presentation: We present a patient with the left-sided subphrenic abscess, formed as a result of insolvency of the esophagojejunal anastomosis after gastrectomy and splenectomy, which underwent percutaneous drainage under the control of ultrasound and X-ray. Sanitation of the abscess cavity and the introduction of fibrin glue into it made it possible to close the fistula and heal the patient. Discussion: The described case shows that the rehabilitation of the abscess and the injection of fibrin glue into it, made it possible to avoid surgery, eliminate the abscess and close the connection with the esophagojejunal anastomosis in a short time. Conclusion: Percutaneous drainage under the control of ultrasound made it possible to avoid surgery and heal the patient with the left-sided subphrenic abscess in a short time. Fistula treatment with fibrin glue is not only effective, but is also less risky than surgery.

© 2019 He et al. Current understanding of flagellum/cilium length regulation focuses on a few model organisms with flagella of uniform length. Leptomonas pyrrhocoris is a monoxenous trypanosomatid parasite of firebugs. When cultivated in vitro, L. pyrrhocoris duplicates every 4.2 ± 0.2 h, representing the shortest doubling time reported for trypanosomatids so far. Each L. pyrrhocoris cell starts its cell cycle with a single flagellum. A new flagellum is assembled de novo, while the old flagellum persists throughout the cell cycle. The flagella in an asynchronous L. pyrrhocoris population exhibited a vast length variation of ∼3 to 24 μm, casting doubt on the presence of a length regulation mechanism based on a single balance point between the assembly and disassembly rate in these cells. Through imaging of live L. pyrrhocoris cells, a rapid, partial disassembly of the existing, old flagellum is observed upon, if not prior to, the initial assembly of a new flagellum. Mathematical modeling demonstrated an inverse correlation between the flagellar growth rate and flagellar length and inferred the presence of distinct, cell cycle-dependent disassembly mechanisms with different rates. On the basis of these observations, we proposed a min-max model that could account for the vast flagellar length range observed for asynchronous L. pyrrhocoris. This model may also apply to other flagellated organisms with flagellar length variation. IMPORTANCE Current understanding of flagellum biogenesis during the cell cycle in trypanosomatids is limited to a few pathogenic species, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The most notable characteristics of trypanosomatid flagella studied so far are the extreme stability and lack of ciliary disassembly/absorption during the cell cycle. This is different from cilia in Chlamydomonas and mammalian cells, which undergo complete absorption prior to cell cycle initiation. In this study, we examined flagellum duplication during the cell cycle of Leptomonas pyrrhocoris. With the shortest duplication time documented for all Trypanosomatidae and its amenability to culture on agarose gel with limited mobility, we were able to image these cells through the cell cycle. Rapid, cell cycle-specific flagellum disassembly different from turnover was observed for the first time in trypanosomatids. Given the observed length-dependent growth rate and the presence of different disassembly mechanisms, we proposed a min-max model that can account for the flagellar length variation observed in L. pyrrhocoris.

© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley  &  Sons Ltd Objectives: To describe, step by step, a new one-stage dorsal skin flap urethroplasty for penile stricture repair. Materials and Methods: The surgery was accomplished through a midline incision on the ventral penile surface, the urethra was fully dissected from the corpora cavernosa and longitudinally opened along its dorsal surface. A penile skin island, based on the dartos fascia flap, was dissected and moved over the corpora cavernosa, and the urethra was moved and sutured over the penile skin flap. Results: Out of the 12 cases, 10 were classified successful and there were two failures. The operating time was 60 min. There was no postoperative fistula or urethral diverticulum. Conclusion: Our modified Orandi's technique was easy and feasible, and avoided fistula and diverticulum formation after repair.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Background: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major cause of viral persistence in patients with chronic HBV infection. Understanding the mechanisms underlying stability and persistence of HBV cccDNA in hepatocytes is critical for developing novel therapeutics and managing chronic hepatitis B. In this study, we observed an unexpected increase in HBV cccDNA levels upon suppression of transcription by de novo DNA methyltransferase DNMT3A and uncovered additional mechanisms potentially involved in HBV cccDNA maintenance. Methods: HBV-expressing cell lines were transfected with a DNMT3A-expressing plasmid. Real-time PCR and HBsAg assays were used to assess the HBV replication rate. Cell cycling was analyzed by fluorescent cell sorting. CRISPR/Cas9 was utilized to abrogate expression of APOBEC3A and APOBEC3B. Alterations in the expression of target genes were measured by real-time PCR. Results: Similar to previous studies, HBV replication induced DNMT3A expression, which in turn, led to reduced HBV transcription but elevated HBV cccDNA levels (4-to 6-fold increase). Increased levels of HBV cccDNA were not related to cell cycling, as DNMT3A accelerated proliferation of infected cells and could not contribute to HBV cccDNA expansion by arresting cells in a quiescent state. At the same time, DNMT3A suppressed transcription of innate immunity factors including cytidine deaminases APOBEC3A and APOBEC3B. CRISPR/Cas9-mediated silencing of APOBEC3A and APOBEC3B transcription had minor effects on HBV transcription, but significantly increased HBV cccDNA levels, similar to DNMT3A. In an attempt to further analyze the detrimental effects of HBV and DNMT3A on infected cells, we visualized γ-H2AX foci and demonstrated that HBV inflicts and DNMT3A aggravates DNA damage, possibly by downregulating DNA damage response factors. Additionally, suppression of HBV replication by DNMT3A may be related to reduced ATM/ATR expression. Conclusion: Formation and maintenance of HBV cccDNA pools may be partially suppressed by the baseline expression of host inhibitory factors including APOBEC3A and APOBEC3B. HBV inflicts DNA damage both directly and by inducing DNMT3A expression.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The relative age effect (RAE) has been well studied in adolescent and adult soccer players; however, less information has been available about children engaged in regular soccer training and the role of performance. Thus, the aim of the present study was to examine the prevalence of RAE in children and adolescent soccer players, as well as the role of age and performance. Russian soccer players (n = 10,446) of various ages, playing positions and performance levels were examined for their date of birth. It was observed that RAE was widespread in Russian soccer teams of all age groups. RAE was most pronounced in children teams of the top tier Russian soccer academies and junior Russia national teams, where the proportions of soccer players born in the first quarter were 43.9% and 39.8%, respectively, whereas those born in the fourth quarter of the year were 7.7% and 6.3%, respectively. In top tier soccer academies, RAE did not vary by age group. In the middle tier soccer academies, RAE was less pronounced. It was still prevalent in the junior teams of the top tier clubs of the Russian Premier League, where 14.3% of the soccer players were born in the fourth quarter of the year compared to 42.9% born in the first quarter of the year. RAE can be observed in the top tier Russian adult teams as well, although it is less pronounced there. In summary, RAE is highly prevalent in Russian children and junior soccer and is associated with the level of competitiveness. At the same time, the proportion of players born in the fourth quarter of the year is higher in adult teams than in junior and youth teams, which is most likely due to the wider selection of players, not limited by their age and place of residence. In junior teams, RAE results in a bias towards selection of players who are more physically mature, whereas children who may be more talented but are less developed due to their younger chronological age tend to be overlooked.

Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose of reviewThe frequency of hospitalization for anaphylaxis has increased over the last 20 years across Europe, Australia, and North America, particularly, for food and medication triggers. Adolescents show the highest risk for morbidity and fatality from food-induced anaphylaxis, yet there is little high-quality evidence addressing the reasons for this disproportionate vulnerability.Recent findingsRecent data seem to suggest a possible increasing burden of food-induced anaphylaxis among adolescents. Trends in anaphylaxis mortality are stable in North America and the United Kingdom, but not in Australia where the incidence of fatal anaphylaxis has recently doubled. The age distribution of fatal anaphylaxis varies according to the nature of the culprit trigger, with data suggesting an age-related predisposition to fatal food anaphylaxis in adolescents and young adults. Adolescence represents a critical phase of transition when rapid and substantial physical, emotional, and social changes occur. Therefore, adolescents show challenges in self-management that are different from other age groups, contributing to a higher risk of poor anaphylaxis outcomes.SummaryThe purpose of this review is to summarize recent data on epidemiology and elicitors of anaphylaxis in adolescents and to address currently known barriers and potential facilitators to self-management of anaphylaxis in this vulnerable age group.

© 2019, Pediatria Ltd. All rights reserved. Acute kidney damage (AKD) is characterized by rapidly progressing organ dysfunction, which often results in development of chronic kidney disease. There are difficulties in diagnosing initial stages of kidney damage, which are usually reversible. Molecular diagnostics is a sensitive method that can detect early nephron changes that are not detectable by conventional methods (by assessing serum creatinine and urinary albumin in urine, diuresis) before renal filtration function decrease. The review examines markers of AKD development key stages: Ischemia (Kidney Injury Molecule-1 (KIM-1), Clusterin), hypoxia (Vascular Endothelial Growth Factor), Hypoxia Inducible Factor (HIF)), inflammation (Monocyte Chemoattractact Protein-1 (MCP-1), Interleukin 18 (IL18)), kidney tubule damage proximal (Beta-2-Microglobulin (B2M), Cystatin C, Neutrophil gelatinase associated lipocalin (NGAL)), distal (NGAL, Calbindin, Osteopontin). The study of these biomarkers in children's urine can be recommended for non-invasive screening, diagnosis and monitoring of AKD.

© 2019, Pediatria Ltd. All rights reserved. In the article the authors present relevant information on the criteria for assessing the activity of juvenile dermatomyositis (JDM) and modern approaches to its treatment. In clinical practice, various scales are currently used to assess the overall JDM activity and severity of damage to various organs, primarily muscles and skin. The article provides modern recommendations for JDM treatment: The use of glucocorticosteroids, disease-modifying antirheumatic drugs (methotrexate, calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, hydroxychloroquine, intravenous immunoglobulin), genetically engineered drugs (rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept), as well as promising new drugs and methods of maintenance therapy. The modern JDM treatment algorithm is described.

© 2019, Pediatria Ltd. All rights reserved. Urinary tract infection (UTI) is one of the most common diseases of the urinary system faced by pediatricians. Objective of the research: To study and analyze outpatient records of patients in their first year of life, sent to a nephrologist for a consultation due to microbial inflammatory changes in urine general analysis. Materials and methods: Outpatient records of 160 children aged from 1 month to 1 year, who were sent in 2017 for a consultation with a nephrologist in consultative diagnostic clinic of G.N. Speransky City Children's Hospital № 9 with directing diagnosis UTI. Results: Authors performed an assessment of guiding diagnoses, age and gender composition of patients, an assessment of life anamnesis and disease clinical symptoms dynamics before referring patients for consultation with a nephrologist. The article discusses mistakes and issues of diagnosing UTI in young children. Conclusion: Authors substantiates pediatrician’s tactics for timely UTI diagnosis in young children and correct tactics of managing these patients.