Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review
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01.09.2019 |
Khaleva E.
Gridneva Z.
Geddes D.
Oddy W.
Colicino S.
Blyuss O.
Boyle R.
Warner J.
Munblit D.
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Clinical and Experimental Allergy |
10.1111/cea.13409 |
4 |
Ссылка
© 2019 John Wiley & Sons Ltd Background: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and clinical relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.
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The efficiency of Governmental and WFP UN Programs for improvement of nutritional status in Tajik schoolchildren as assessed by dietary intake and hair trace element content
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01.09.2019 |
Kirichuk A.
Skalny A.
Dodkhoyev J.
Skalnaya M.
Grabeklis A.
Ajsuvakova O.
Tinkov A.
Notova S.
Bjørklund G.
Tinkova M.
Chizhov A.
Bobrovnitskiy I.
Bolotnikova E.
Chernigov V.
Skalny A.
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Journal of Trace Elements in Medicine and Biology |
10.1016/j.jtemb.2019.06.018 |
0 |
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© 2019 Elsevier GmbH Background: The objective of the study was to assess hair trace element and mineral content in children undergoing WFP UN and the governmental programs of school nutrition in Tajikistan. Methods: WFP program included provision or wheat flour fortified with micronutrients including Fe and Zn, and iodized salt, whereas within the governmental program hot meals were provided. A total of 202 children studying in schools that were not (Type 1, n = 100) or were involved in dietary intervention programs (Type 2, n = 102). Food and hair trace element content was assessed using ICP-MS. Results: Daily intake of Fe, I, Zn, B, Co, Mg, Si, and Sr in Type 2 schools was more than 2.5, 12, 4, 2.9, 2.6, 2, 3, and 2-fold higher than that in Type 1 schools. Correspondingly, anthropometric parameters in children from Type 2 schools exceeded the control values. Surprisingly, no significant difference in hair iodine levels was detected. Hair analysis demonstrated a significant increase in hair Ca, Mg, Na, Co, Cr, Cu, Fe, Li, Mn, Se, V, Zn content. Certain toxic elements including Al, As, and Be were also characterized by an increase in Type 2 schools. At the same time, nutritional intervention was associated with a significant decrease in hair B, Hg, and Sn levels. Conclusions: Nutritional intervention within WFP and the governmental program was effective in increasing essential trace element supply in Tajik schoolchildren. However, further studies including a detailed assessment of nutritional and health status with a special focus on iodine and thyroid functioning are required.
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Prospective evaluation of the performance of [<sup>68</sup>Ga]Ga-PSMA-11 PET/CT(MRI) for lymph node staging in patients undergoing superextended salvage lymph node dissection after radical prostatectomy
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01.09.2019 |
Abufaraj M.
Grubmüller B.
Zeitlinger M.
Kramer G.
Seitz C.
Haitel A.
Baltzer P.
Hacker M.
Wadsak W.
Pfaff S.
Wiatr T.
Mitterhauser M.
Shariat S.
Hartenbach M.
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European Journal of Nuclear Medicine and Molecular Imaging |
10.1007/s00259-019-04361-0 |
1 |
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© 2019, The Author(s). Purpose: To assess the accuracy of [68Ga]-PSMA-11 PET/CT or [68Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Patients and methods: In a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND. Results: The median age of the patients at the time of SLND was 65 years (IQR 63–69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8–2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33–48) and the median number of positive nodes was 4 (IQR 2–6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3–9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1–5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively. Conclusion: PSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.
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Neutropenia during tocilizumab treatment is not associated with infection risk in systemic or polyarticular-course juvenile idiopathic arthritis
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01.09.2019 |
Pardeo M.
Wang J.
Ruperto N.
Alexeeva E.
Chasnyk V.
Schneider R.
Horneff G.
Huppertz H.
Minden K.
Onel K.
Zemel L.
Martin A.
Koné-Paut I.
Siamopoulou-Mavridou A.
Silva C.
Porter-Brown B.
Bharucha K.
Brunner H.
De Benedetti F.
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Journal of Rheumatology |
10.3899/jrheum.180795 |
0 |
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© 2019 The Journal of Rheumatology. All rights reserved. Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.
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Alcohol use disorders
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31.08.2019 |
Carvalho A.
Heilig M.
Perez A.
Probst C.
Rehm J.
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The Lancet |
10.1016/S0140-6736(19)31775-1 |
3 |
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© 2019 Elsevier Ltd Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. Despite their high prevalence, alcohol use disorders are undertreated partly because of the high stigma associated with them, but also because of insufficient systematic screening in primary health care, although effective and cost-effective psychosocial and pharmacological interventions do exist. Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.
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Tspan18 is a novel regulator of the Ca<sup>2+</sup> channel Orai1 and von Willebrand factor release in endothelial cells
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31.08.2019 |
Noy P.
Gavin R.
Colombo D.
Haining E.
Reyat J.
Payne H.
Thielmann I.
Lokman A.
Neag G.
Yang J.
Lloyd T.
Harrison N.
Heath V.
Gardiner C.
Whitworth K.
Robinson J.
Koo C.
Maio A.
Harrison P.
Lee S.
Michelangeli F.
Kalia N.
Rainger G.
Nieswandt B.
Brill A.
Watson S.
Tomlinson M.
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Haematologica |
10.3324/haematol.2018.194241 |
1 |
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© 2019 Ferrata Storti Foundation. Ca2+ entry via Orai1 store-operated Ca2+ channels in the plasma membrane is critical to cell function, and Orai1 loss causes severe immunodeficiency and developmental defects. The tetraspanins are a superfamily of transmembrane proteins that interact with specific 'partner proteins' and regulate their trafficking and clustering. The aim of this study was to functionally characterize tetraspanin Tspan18. We show that Tspan18 is expressed by endothelial cells at several-fold higher levels than most other cell types analyzed. Tspan18-knockdown primary human umbilical vein endothelial cells have 55-70% decreased Ca2+ mobilization upon stimulation with the inflammatory mediators thrombin or histamine, similar to Orai1-knockdown. Tspan18 interacts with Orai1, and Orai1 cell surface localization is reduced by 70% in Tspan18-knockdown endothelial cells. Tspan18 overexpression in lymphocyte model cell lines induces 20-fold activation of Ca2+ -responsive nuclear factor of activated T cell (NFAT) signaling, in an Orai1-dependent manner. Tspan18-knockout mice are viable. They lose on average 6-fold more blood in a tail-bleed assay. This is due to Tspan18 deficiency in non-hematopoietic cells, as assessed using chimeric mice. Tspan18- knockout mice have 60% reduced thrombus size in a deep vein thrombosis model, and 50% reduced platelet deposition in the microcirculation following myocardial ischemia-reperfusion injury. Histamine- or thrombin-induced von Willebrand factor release from endothelial cells is reduced by 90% following Tspan18-knockdown, and histamine-induced increase of plasma von Willebrand factor is reduced by 45% in Tspan18- knockout mice. These findings identify Tspan18 as a novel regulator of endothelial cell Orai1/Ca2+ signaling and von Willebrand factor release in response to inflammatory stimuli.
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Prospective evaluation of pregnancy outcome in an Italian woman with late-onset combined homocystinuria and methylmalonic aciduria
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30.08.2019 |
Grandone E.
Martinelli P.
Villani M.
Vecchione G.
Fischetti L.
Leccese A.
Santacroce R.
Corso G.
Margaglione M.
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BMC Pregnancy and Childbirth |
10.1186/s12884-019-2474-5 |
0 |
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© 2019 The Author(s). Background: Cobalamin metabolism disorders are rare, inherited diseases which cause megaloblastic anaemia and other clinical manifestations. Early diagnosis of these conditions is essential, in order to allow appropriate treatment as early as possible. Case presentation: Here we report the case of a patient who was apparently healthy until the age of 20, when she presented with impaired renal function and normocytic anaemia. At the age of 34, when her first pregnancy resulted in an intrauterine death of a morphologically normal growth-restricted foetus, she was diagnosed with homocystinuria and methylmalonic aciduria due to cyanocobalamin C (cblC) defect, which was confirmed by molecular investigation. Consequently, hydroxocobalamin was administered to correct homocysteine plasma levels. This treatment was efficacious in lowering homocysteine plasma levels and restored anaemia and renal function. During a second pregnancy, the patient was also administered a prophylactic dose of low molecular -weight heparin. The pregnancy concluded with a full-term delivery of a healthy male. Conclusions: This case emphasises the importance of awareness and appropriate management of rare metabolic diseases during pregnancy. We suggest that women with late-onset cblC defect can have a positive pregnancy outcome if this metabolic disease is treated adequately.
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Transcript Analysis of Zebrafish GLUT3 Genes, slc2a3a and slc2a3b, Define Overlapping as Well as Distinct Expression Domains in the Zebrafish (Danio rerio) Central Nervous System
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27.08.2019 |
Lechermeier C.
Zimmer F.
Lüffe T.
Lesch K.
Romanos M.
Lillesaar C.
Drepper C.
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Frontiers in Molecular Neuroscience |
10.3389/fnmol.2019.00199 |
0 |
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© Copyright © 2019 Lechermeier, Zimmer, Lüffe, Lesch, Romanos, Lillesaar and Drepper. The transport of glucose across the cell plasma membrane is vital to most mammalian cells. The glucose transporter (GLUT; also called SLC2A) family of transmembrane solute carriers is responsible for this function in vivo. GLUT proteins encompass 14 different isoforms in humans with different cell type-specific expression patterns and activities. Central to glucose utilization and delivery in the brain is the neuronally expressed GLUT3. Recent research has shown an involvement of GLUT3 genetic variation or altered expression in several different brain disorders, including Huntington’s and Alzheimer’s diseases. Furthermore, GLUT3 was identified as a potential risk gene for multiple psychiatric disorders. To study the role of GLUT3 in brain function and disease a more detailed knowledge of its expression in model organisms is needed. Zebrafish (Danio rerio) has in recent years gained popularity as a model organism for brain research and is now well-established for modeling psychiatric disorders. Here, we have analyzed the sequence of GLUT3 orthologs and identified two paralogous genes in the zebrafish, slc2a3a and slc2a3b. Interestingly, the Glut3b protein sequence contains a unique stretch of amino acids, which may be important for functional regulation. The slc2a3a transcript is detectable in the central nervous system including distinct cellular populations in telencephalon, diencephalon, mesencephalon and rhombencephalon at embryonic and larval stages. Conversely, the slc2a3b transcript shows a rather diffuse expression pattern at different embryonic stages and brain regions. Expression of slc2a3a is maintained in the adult brain and is found in the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The slc2a3b transcripts are present in overlapping as well as distinct regions compared to slc2a3a. Double in situ hybridizations were used to demonstrate that slc2a3a is expressed by some GABAergic neurons at embryonic stages. This detailed description of zebrafish slc2a3a and slc2a3b expression at developmental and adult stages paves the way for further investigations of normal GLUT3 function and its role in brain disorders.
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Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses
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20.08.2019 |
Rasche A.
Lehmann F.
König A.
Goldmann N.
Corman V.
Moreira-Soto A.
Geipel A.
van Riel D.
Vakulenko Y.
Sander A.
Niekamp H.
Kepper R.
Schlegel M.
Akoua-Koffi C.
Souza B.
Sahr F.
Olayemi A.
Schulze V.
Petraityte-Burneikiene R.
Kazaks A.
Lowjaga K.
Geyer J.
Kuiken T.
Drosten C.
Lukashev A.
Fichet-Calvet E.
Ulrich R.
Glebe D.
Drexler J.
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Proceedings of the National Academy of Sciences of the United States of America |
10.1073/pnas.1908072116 |
0 |
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© 2019 National Academy of Sciences. All rights reserved. Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.
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Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel
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15.08.2019 |
Mirzaev K.
Samsonova K.
Potapov P.
Andreev D.
Grishina E.
Ryzhikova K.
Sychev D.
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Molecular Biology Reports |
10.1007/s11033-019-04871-y |
0 |
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© 2019, Springer Nature B.V. The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.
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Combination of low-temperature electrosurgical unit and extractive electrospray ionization mass spectrometry for molecular profiling and classification of tissues
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15.08.2019 |
Sukhikh G.
Chagovets V.
Wang X.
Rodionov V.
Kometova V.
Tokareva A.
Kononikhin A.
Starodubtseva N.
Chingin K.
Chen H.
Frankevich V.
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Molecules |
10.3390/molecules24162957 |
0 |
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© 2019 by the authors. Real-time molecular navigation of tissue surgeries is an important goal at present. Combination of electrosurgical units and mass spectrometry (MS) to perform accurate molecular visualization of biological tissues has been pursued by many research groups. Determination of molecular tissue composition at a particular location by surgical smoke analysis is now of increasing interest for clinical use. However, molecular analysis of surgical smoke is commonly lacking molecular specificity and is associated with significant carbonization and chemical contamination, which are mainly related to the high temperature of smoke at which many molecules become unstable. Unlike traditional electrosurgical tools, low-temperature electrosurgical units allow tissue dissection without substantial heating. Here, we show that low-temperature electrosurgical units can be used for desorption of molecules from biological tissues without thermal degradation. The use of extractive electrospray ionization technique for the ionization of desorbed molecules allowed us to obtain mass spectra of healthy and pathological tissues with high degree of differentiation. Overall, the data indicate that the described approach has potential for intraoperative use.
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Chronic effects of platinum(IV) complex and its diamine ligand on rat heart function: comparison with cisplatin
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15.08.2019 |
Smigic J.
Sabo T.
Vranic A.
Zivkovic V.
Srejovic I.
Turnic T.
Milosavljevic I.
Poljarevic J.
Krivokapic M.
Bolevich S.
Jakovljevic V.
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Molecular and Cellular Biochemistry |
10.1007/s11010-019-03533-8 |
0 |
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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40–120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a “gold standard”, novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.
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Tortuosity of the superficial femoral artery and its influence on blood flow patterns and risk of atherosclerosis
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15.08.2019 |
Li X.
Liu X.
Li X.
Xu L.
Chen X.
Liang F.
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Biomechanics and Modeling in Mechanobiology |
10.1007/s10237-019-01118-4 |
0 |
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© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. The superficial femoral artery (SFA) is a typical atherosclerosis-prone site. We aimed to explore whether the tortuosity of the SFA associates with the occurrence of atherosclerosis and investigate how vascular tortuosity influences the characteristics of blood flow. Ten patients diagnosed with atherosclerotic disease in their SFAs while free of systemic atherosclerosis risk factors were enrolled together with ten atherosclerosis-free patients. The tortuosity of each SFA was quantitatively evaluated by calculating the averaged curvature (AC), maximum curvature (MC) and fraction of high curvature (FC) based on the geometrical model reconstructed from medical images. Hemodynamic studies were performed using both geometrically simplified and anatomically realistic models of the SFA to systematically address the hemodynamic effects of vascular tortuosity. Morphological analyses revealed that all curvature indices of the SFA were significantly larger in patients with atherosclerosis than in atherosclerosis-free patients (AC [mm−1]: 0.034 ± 0.016 vs. 0.018 ± 0.006; MC [mm−1]: 0.055 ± 0.023 vs. 0.034 ± 0.008; FC [%]: 22.77 ± 10.22 vs. 11.39 ± 6.82; p < 0.001). Simulations of blood flows in the geometrically simplified SFAs showed that increasing vascular curvature caused a progressive increase in the area ratios of low wall shear stress (LWSA) and high oscillatory shear index (HOSA). Hemodynamic studies on the anatomically realistic SFAs further demonstrated that high-curvature SFAs (n = 10) had overall larger LWSA and HOSA compared with low-curvature SFAs (n = 10) (LWSA [%]: 4.13 ± 1.91 vs. 1.79 ± 1.13, p = 0.009; HOSA [%]: 4.95 ± 1.92 vs. 2.37 ± 1.51, p = 0.007). These results suggest that increased vascular tortuosity augments the severity and distribution of atherosclerosis-promoting flow disturbances in the SFA and may be an independent risk factor for atherosclerosis.
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Determination of S-adenosylmethionine and S-adenosylhomocysteine in blood plasma by UPLC with fluorescence detection
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15.08.2019 |
Ivanov A.
Dubchenko E.
Kruglova M.
Virus E.
Bulgakova P.
Alexandrin V.
Fedoseev A.
Boyko A.
Grachev S.
Kubatiev A.
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Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences |
10.1016/j.jchromb.2019.06.032 |
0 |
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© 2019 Elsevier B.V. A validated approach to determine various methionine cycle metabolites (S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine) in human blood plasma is offered. The approach is based on solid-phase extraction (with grafted phenylboronic acid) and derivatization with chloroacetaldehyde followed by ultra-performance liquid chromatography with fluorescence detection. We used a 100 × 2.1 mm × 1.8 μm C18 column for the selective separation of analytes. Chromatographic separation was achieved with gradient elution of acetonitrile (flow rate 0.2 mL/min) from 2 to 20%. The eluent was initially composed of 10 mM KH2PO4 with 10 mM acetic acid and 25 μM heptafluorobutyric acid. The total analysis time was 11 min. Validation of the method included detection of the limit of detection (2 nM), limit of quantification (5 nM), accuracy (97.2–101%), and intra- and interday precision (2.2–9.0%). Analysis of plasma samples from healthy volunteers revealed that the average levels of S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine were 93.6, 20.9 and 14.8 nM, respectively.
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Rationale and design of two prospective, multicenter, observational studies on reproductive outcome in women with recurrent failures after spontaneous or assisted conception: OTTILIA and FIRST registries
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13.08.2019 |
Villani M.
Baldini D.
Totaro P.
Larciprete G.
Kovac M.
Carone D.
Passamonti S.
Permunian E.
Bartolotti T.
Lojacono A.
Cacciola R.
Pinto G.
Bucherini E.
De Stefano V.
Lodigiani C.
Lavopa C.
Cho Y.
Pizzicaroli C.
Colaizzo D.
Grandone E.
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BMC Pregnancy and Childbirth |
10.1186/s12884-019-2444-y |
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© 2019 The Author(s). Background: Spontaneous pregnancy loss and implantation failure after assisted reproductive technologies (ART) are very common occurrences. Although 50-60% of all cases remains unexplained, various predisposing factors, including thrombophilias, have been identified. Thus, the potential benefit of a prophylaxis with low-molecular-weight heparins in improving outcomes has been often investigated over the years. However, the majority of studies are observational and results from randomized clinical trials (RCTs) are inconclusive, probably due to heterogeneity and limited sample size. To cover these unmet needs and to have further data mainly based on the real-life clinical management, we designed these multicenter registries. Methods: OTTILIA (Observational sTudy on antiThrombotic prevention in thrombophILIA and pregnancy loss) and FIRST (recurrent Failures in assIsted Reproductive Techniques) registries are two prospective, multicenter, observational studies to evaluate pregnancy or ART outcomes in consecutive women with previous reproductive failures after spontaneous or assisted conception, respectively. All enrolled women are observed from their first visit after positive pregnancy test (OTTILIA) or before commencing a new ART cycle (FIRST) until the end of pregnancy or ART procedure (negative pregnancy test/end of pregnancy, if successful cycle), respectively. Data are collected by means of questionnaires and recorded in a central database. Follow-up investigations are performed during hospital stay, routine clinical follow-up visits or telephone interviews. Primary outcome is live birth rate in the OTTILIA register and clinical pregnancy rate in the FIRST. Discussion: Although RCTs are the 'gold standard' for evaluating treatment outcomes, we believe that our registries represent a valid alternative in improving knowledge on mechanisms involved in reproductive failures and supporting future clinical decisions. Trial registration: NCT 02385461, retrospectively registered 5 March 2015 (OTTILIA); NCT 02685800, registered 10 February 2016 (FIRST).
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Combined magnetic field sensor with nanoscale elements
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09.08.2019 |
Ichkitidze L.
Selishchev S.
Potapov D.
Telyshev D.
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AIP Conference Proceedings |
10.1063/1.5121953 |
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© 2019 Author(s). A combined magnetic field sensor consisting of a magnetic field concentrator based on a superconducting ring film and a magnetically sensitive element with a spintronics structure is investigated. It had a sandwich structure. It is established that the coefficient of concentration of the magnetic field increases due to fragmentation of the active band, in the form of several superconducting branches and cuts having nanoscale widths (≥20 nm). With an increase in the number of cuts, the threshold magnetosensitivity of the sensor also decreases several times. Nanoscale elements in the form of cuts in the active strip make it possible to reduce the diameter of the concentrator ring and the sensor as a whole smaller than 1 mm. It is noted that the considered combined magnetic field sensor with nanoscale elements has a high potential for detecting ultraweak magnetic fields (∼10 pT).
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Mathematical modeling of the Fontan circulation - Ventricular assist device interaction
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09.08.2019 |
Rubtsova E.
Markov A.
Telyshev D.
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AIP Conference Proceedings |
10.1063/1.5121983 |
0 |
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© 2019 Author(s). The Fontan procedure is performed for univentricular correction of the heart in pediatric patients with tricuspid atresia. It brings a great contribution to the improvement of mortality in patients with a single ventricle. However, as a result of the procedure the load on the single functional ventricle of the heart and veins increases. Eventually, patients need a heart transplantation. As a possible solution to the circulation deficiencies of the Fontan patients can be the ventricular assist device (VAD). The VAD is implanted between veins and the pulmonary artery. In order to decrease the amount of in vitro tests, we use the electro-hydraulic analogy, where the cardiovascular system (CVS) is represented as an electrical circuit. It allows as tointroduce mathematical nonlinear models with lumped parameters of the Fontan univentricular circulation and its interaction with the VAD. Appling VAD to the Fontan patients brings possibility to increase the venous return of blood. According to the Frank-Starling law, the stroke volume increases with increasing venous return. VAD creates a necessary pressure differential between the venous and pulmonary sections of CVS. The interaction model of the Fontan circulation with VAD support demonstrates the normalization of the pressures and volumes distribution in the CVS. This indicates that the method studied in this work might be an ideal way to optimize the health condition of patients after Fontan procedure.
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Animal trials of closed-loop insulin delivery system based on continuous non-invasive glucose monitoring
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09.08.2019 |
Pozhar K.
Litinskaia E.
Rudenko P.
Bazaev N.
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AIP Conference Proceedings |
10.1063/1.5121975 |
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© 2019 Author(s). The work is dedicated to animal trials of closed-loop insulin delivery system with non-invasive NIR-spectroscopic glucose monitor and model predictive control based on empirical sigma-model of BG dynamics. The trials were aimed on verification of safety and efficiency of the smartphone controlled closed-loop operation in interaction with living organism. As a subject of trials 1 female outbred dog with steroid diabetes were used. During 24 hours closed-loop worked in automatic insulin therapy mode with defined BG maintaining ranges 75-150 and 75-250 mg/dl (each for 12 hours). The tests showed that mean absolute percentage error was less than 23 % in BG range 50-100 mg/dl and less than 20 % in BG range of 100-250 mg/dl. 95.8 % of measurements fall in zones A and B (Clarke error grid). The closed loop enables to maintain animal BG in defined ranges with maximum deviation of 22.1 %. Since during the experiment no battery-low messages were displayed, continuous operation time was more than 24 hours. The animal trials results fir with investigation tests.
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Investigation of albumin denaturation when exposed to a nanosecond laser source
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09.08.2019 |
Savelyev M.
Agafonova N.
Vasilevsky P.
Ryabkin D.
Gerasimenko A.
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AIP Conference Proceedings |
10.1063/1.5121988 |
0 |
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© 2019 Author(s). In this article, the processes of protein denaturation in an aqueous dispersion with the presence of single-walled carbon nanotubes under the influence of near-IR laser radiation are investigated. For irradiation, a pulsed solid-state Nd: YAG laser with a wavelength of 1064 nm was used, the irradiation time was 10 minutes, the pulse repetition rate was 10 Hz, and the duration was 16 ns. The sample temperature during the experiment was measured using a pyrometer. It was found that in protein dispersions without carbon nanotubes at a power of incident radiation of ∼1 W, denaturation did not occur, while in dispersions with nanotubes at a temperature of 45-55 °C a decrease in sample transmission was observed, which indicates the occurrence of albumin protein denaturation. Denaturation of protein in dispersions with carbon nanotubes is explained by an increase in the absorption of laser radiation due to the appearance of nonlinear optical effects.
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Hardness maps analysis of the layered nanocomposites for tissue repair of the cardiovascular system
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09.08.2019 |
Gerasimenko A.
Ichkitidze L.
Kurilova U.
Murashko D.
Potapov D.
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AIP Conference Proceedings |
10.1063/1.5121947 |
1 |
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© 2019 Author(s). The hardness characteristic of layered nanocomposites based on single-walled carbon nanotubes in the biological matrices of albumin, collagen proteins and also the amino sugar of chitosa are investigated. Nanocomposites are formed by layer-by-layer near IR pulsed laser evaporation of aquatic biological matrices with nanotubes. Maps of the distribution of hardness of nanocomposites at depths 200-1000 nm were constructed using the scanning indentation method. Analysis of the maps made possible to demonstrate the structural characteristics of nanocomposites - the distribution of carbon nanotube bundles over the volume of nanocomposites. The hardness of nanocomposites ranged from 50 to 600 MPa. The results indicate the possibility of using nanocomposites based on single-walled carbon nanotubes with a diameter of 1.5-1.6 nm and a length of 7-8 μm in tissue engineering of the cardiovascular system.
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