Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide
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01.12.2019 |
Akasov R.
Sholina N.
Khochenkov D.
Alova A.
Gorelkin P.
Erofeev A.
Generalova A.
Khaydukov E.
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Scientific Reports |
10.1038/s41598-019-46115-w |
0 |
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© 2019, The Author(s). Melanoma is one of the most aggressive and lethal form of cancer. Photodynamic therapy (PDT) is a clinically approved technique for cancer treatment, including non-melanoma skin cancer. However, the most of conventional photosensitizers are of low efficacy against melanoma due to the possible dark toxicity at high drug concentrations, melanin pigmentation, and induction of anti-oxidant defense mechanisms. In the current research we propose non-toxic flavin mononucleotide (FMN), which is a water-soluble form of riboflavin (vitamin B2) as a promising agent for photodynamic therapy of melanoma. We demonstrated selective accumulation of FMN in melanoma cells in vivo and in vitro in comparison with keratinocytes and fibroblasts. Blue light irradiation with dose 5 J/cm2 of melanoma cells pre-incubated with FMN led to cell death through apoptosis. Thus, the IC50 values of human melanoma A375, Mel IL, and Mel Z cells were in a range of FMN concentration 10–30 µM that can be achieved in tumor tissue under systemic administration. The efficiency of reactive oxygen species (ROS) generation under FMN blue light irradiation was measured in single melanoma cells by a label-free technique using an electrochemical nanoprobe in a real-time control manner. Melanoma xenograft regression in mice was observed as a result of intravenous injection of FMN followed by blue-light irradiation of tumor site. The inhibition of tumor growth was 85–90% within 50 days after PDT treatment.
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Tissue Engineered Neural Constructs Composed of Neural Precursor Cells, Recombinant Spidroin and PRP for Neural Tissue Regeneration
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01.12.2019 |
Baklaushev V.
Bogush V.
Kalsin V.
Sovetnikov N.
Samoilova E.
Revkova V.
Sidoruk K.
Konoplyannikov M.
Timashev P.
Kotova S.
Yushkov K.
Averyanov A.
Troitskiy A.
Ahlfors J.
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Scientific Reports |
10.1038/s41598-019-39341-9 |
2 |
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© 2019, The Author(s). We have designed a novel two-component matrix (SPRPix) for the encapsulation of directly reprogrammed human neural precursor cells (drNPC). The matrix is comprised of 1) a solid anisotropic complex scaffold prepared by electrospinning a mixture of recombinant analogues of the spider dragline silk proteins – spidroin 1 (rS1/9) and spidroin 2 (rS2/12) - and polycaprolactone (PCL) (rSS-PCL), and 2) a “liquid matrix” based on platelet-rich plasma (PRP). The combination of PRP and spidroin promoted drNPC proliferation with the formation of neural tissue organoids and dramatically activated neurogenesis. Differentiation of drNPCs generated large numbers of βIII-tubulin and MAP2 positive neurons as well as some GFAP-positive astrocytes, which likely had a neuronal supporting function. Interestingly the SPRPix microfibrils appeared to provide strong guidance cues as the differentiating neurons oriented their processes parallel to them. Implantation of the SPRPix matrix containing human drNPC into the brain and spinal cord of two healthy Rhesus macaque monkeys showed good biocompatibility: no astroglial and microglial reaction was present around the implanted construct. Importantly, the human drNPCs survived for the 3 month study period and differentiated into MAP2 positive neurons. Tissue engineered constructs based on SPRPix exhibits important attributes that warrant further examination in spinal cord injury treatment.
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Insect trypanosomatids in Papua New Guinea: high endemism and diversity
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01.12.2019 |
Králová J.
Grybchuk-Ieremenko A.
Votýpka J.
Novotný V.
Kment P.
Lukeš J.
Yurchenko V.
Kostygov A.
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International Journal for Parasitology |
10.1016/j.ijpara.2019.09.004 |
0 |
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© 2019 Australian Society for Parasitology The extreme biological diversity of Oceanian archipelagos has long stimulated research in ecology and evolution. However, parasitic protists in this geographic area remained neglected and no molecular analyses have been carried out to understand the evolutionary patterns and relationships with their hosts. Papua New Guinea (PNG) is a biodiversity hotspot containing over 5% of the world's biodiversity in less than 0.5% of the total land area. In the current work, we examined insect heteropteran hosts collected in PNG for the presence of trypanosomatid parasites. The diversity of insect flagellates was analysed, to our knowledge for the first time, east of Wallace's Line, one of the most distinct biogeographic boundaries of the world. Out of 907 investigated specimens from 138 species and 23 families of the true bugs collected in eight localities, 135 (15%) were infected by at least one trypanosomatid species. High species diversity of captured hosts correlated with high diversity of detected trypanosomatids. Of 46 trypanosomatid Typing Units documented in PNG, only eight were known from other geographic locations, while 38 TUs (~83%) have not been previously encountered. The widespread trypanosomatid TUs were found in both widely distributed and endemic/sub-endemic insects. Approximately one-third of the endemic trypanosomatid TUs were found in widely distributed hosts, while the remaining species were confined to endemic and sub-endemic insects. The TUs from PNG form clades with conspicuous host-parasite coevolutionary patterns, as well as those with a remarkable lack of this trait. In addition, our analysis revealed new members of the subfamilies Leishmaniinae and Strigomonadinae, potentially representing new genera of trypanosomatids.
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Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis
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01.12.2019 |
Mori K.
Kimura S.
Parizi M.
Enikeev D.
Glybochko P.
Seebacher V.
Fajkovic H.
Mostafaei H.
Lysenko I.
Janisch F.
Egawa S.
Shariat S.
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Clinical Genitourinary Cancer |
10.1016/j.clgc.2019.07.009 |
0 |
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© 2019 The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor–axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.
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Ferromagnetic-like behavior of Bi<inf>0.9</inf>La<inf>0.1</inf>FeO<inf>3</inf>–KBr nanocomposites
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01.12.2019 |
Karpinsky D.
Fesenko O.
Silibin M.
Dubkov S.
Chaika M.
Yaremkevich A.
Lukowiak A.
Gerasymchuk Y.
Stręk W.
Pakalniškis A.
Skaudzius R.
Kareiva A.
Fomichov Y.
Shvartsman V.
Kalinin S.
Morozovsky N.
Morozovska A.
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Scientific Reports |
10.1038/s41598-019-46834-0 |
0 |
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© 2019, The Author(s). We studied magnetostatic response of the Bi0.9La0.1FeO3– KBr composites (BLFO-KBr) consisting of nanosized (≈100 nm) ferrite Bi0.9La0.1FeO3 (BLFO) conjugated with fine grinded ionic conducting KBr. When the fraction of KBr is rather small (less than 15 wt%) the magnetic response of the composite is very weak and similar to that observed for the BLFO (pure KBr matrix without Bi1-xLaxFeO3 has no magnetic response as anticipated). However, when the fraction of KBr increases above 15%, the magnetic response of the composite changes substantially and the field dependence of magnetization reveals ferromagnetic-like hysteresis loop with a remanent magnetization about 0.14 emu/g and coercive field about 1.8 Tesla (at room temperature). Nothing similar to the ferromagnetic-like hysteresis loop can be observed in Bi1-zLazFeO3 ceramics with z ≤ 0.15, which magnetization quasi-linearly increases with magnetic field. Different physical mechanisms were considered to explain the unusual experimental results for BLFO-KBr nanocomposites, but only those among them, which are highly sensitive to the interaction of antiferromagnetic Bi0.9La0.1FeO3 with ionic conductor KBr, can be relevant.
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Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
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01.12.2019 |
Gorinski N.
Bijata M.
Prasad S.
Wirth A.
Abdel Galil D.
Zeug A.
Bazovkina D.
Kondaurova E.
Kulikova E.
Ilchibaeva T.
Zareba-Koziol M.
Papaleo F.
Scheggia D.
Kochlamazashvili G.
Dityatev A.
Smyth I.
Krzystyniak A.
Wlodarczyk J.
Richter D.
Strekalova T.
Sigrist S.
Bang C.
Hobuß L.
Fiedler J.
Thum T.
Naumenko V.
Pandey G.
Ponimaskin E.
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Nature Communications |
10.1038/s41467-019-11876-5 |
0 |
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© 2019, The Author(s). The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.
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The effect of radical cystectomy on survival in patients with metastatic urothelial carcinoma of the urinary bladder
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01.12.2019 |
Luzzago S.
Palumbo C.
Rosiello G.
Pecoraro A.
Deuker M.
Tian Z.
Shariat S.
Saad F.
de Cobelli O.
Karakiewicz P.
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Journal of Surgical Oncology |
10.1002/jso.25717 |
0 |
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© 2019 Wiley Periodicals, Inc. Background: To test the effect of radical cystectomy (RC) with chemotherapy vs only chemotherapy on overall mortality (OM) in metastatic urothelial carcinoma of the urinary bladder (mUCUB). Methods: Within the Surveillance, Epidemiology, and End Results registry (2004–2016), we identified patients with mUCUB. Stratification was made according to treatment: RC with chemotherapy vs only chemotherapy. Kaplan-Meier plots and multivariable Cox regression models were used before and after 1:1 propensity score (PS) matching and inverse probability of treatment weighting (IPTW). Results: Of 2414 patients with mUCUB, 500 (21.0%) vs 1914 (79.0%) were treated with RC with chemotherapy vs only chemotherapy, respectively. In multivariable Cox regression models, RC with chemotherapy was associated with lower OM in the overall cohort (hazard ratio [HR], 0.5; P <.001), after 1:1 PS matching (HR, 0.5; P <.001), after IPTW (HR, 0.5; P <.001) and after accounting for number and location of metastases (HR, 0.5; P <.001). However, higher overall survival after RC with chemotherapy was only observed in patients with one metastatic site (21 vs 16 months; P =.001). Conclusion: In contemporary patients with mUCUB, RC with chemotherapy is associated with lower OM rates, relative to chemotherapy alone, but only in patients with a single metastatic site. These individuals accounted for the vast majority of patients in whom an RC was performed, despite the presence of metastatic disease.
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Mechanisms of soil macrofauna community sustainability in temperate rice-growing systems
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01.12.2019 |
Korobushkin D.
Gongalsky K.
Gorbunova A.
Palatov D.
Shekhovtsov S.
Tanasevitch A.
Volkova J.
Chimidov S.
Dedova E.
Ladatko V.
Sunitskaya T.
John K.
Saifutdinov R.
Zaitsev A.
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Scientific Reports |
10.1038/s41598-019-46733-4 |
0 |
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© 2019, The Author(s). Rice growing requires highly destructive and highly invasive field management negatively affecting soil biota and its functions. We aimed to compare taxonomic and functional trait compositions of soil macrofauna at different stages of rice cropping cycles in the three temperate rice-growing regions in Russia. Samples were collected in 2016 at four different biotopes in each region: flooded rice paddies; upland crops planted one year after flooded rice; rice paddy bunds; and relatively undisturbed seminatural control grasslands. Collected soil macrofauna were allocated to different traits according to their feeding preferences, vertical distribution, mobility and flood tolerance. The lowest macrofaunal abundance across all regions was observed in rice paddies. Cultivation of upland crops after paddy flooding consistently decreased the abundance of resident macrofauna, but not that of mobile soil macrofauna. In the upland crops, the abundance of belowground and mobile belowground macrofauna was significantly higher than that in control grasslands. The abundance of aboveground phytophages was significantly lower in the upland crops than in control sites. Flood-associated taxa showed low colonization ability after the paddies were drained. In contrast, representatives of other traits recorded in flooded fields increased their abundance at the next stage of crop rotation, demonstrating high resilience within an entire rice-growing system, including bunds. This finding indicates a high potential of seminatural grasslands and especially bunds as sources of rapid restoration of soil macrofauna functional diversity in rice-growing agroecosystems, thus maintaining the sustainability of soil food webs in the rice paddies.
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Alkoxy aluminum chlorides in the cationic polymerization of isobutylene: A co-initiator, carbocation stabilizer and chain-transfer agent
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28.11.2019 |
Shiman D.
Vasilenko I.
Kostjuk S.
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Polymer Chemistry |
10.1039/c9py01317b |
0 |
Ссылка
© 2019 The Royal Society of Chemistry. Alkoxy aluminum chlorides are efficient catalysts for the preparation of well-defined exo-olefin terminated PIBs of low (Mn ∼ 1000 g mol-1) to medium (Mn up to 50000 g mol-1) molecular weight under mild experimental conditions (n-hexane as a solvent, [IB] = 5.8 M, temperature from -20 °C to 20 °C).
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The architecture of the IgG anti-carbohydrate repertoire in primary antibody deficiencies
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28.11.2019 |
Jandus P.
Boligan K.
Smith D.
de Graauw E.
Grimbacher B.
Jandus C.
Abdelhafez M.
Despont A.
Bovin N.
Simon D.
Rieben R.
Simon H.
Cummings R.
von Gunten S.
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Blood |
10.1182/blood.2019001705 |
1 |
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© 2019 by The American Society of Hematology. Immune system failure in primary antibody deficiencies (PADs) has been linked to recurrent infections, autoimmunity, and cancer, yet clinical judgment is often based on the reactivity to a restricted panel of antigens. Previously, we demonstrated that the human repertoire of carbohydrate-specific immunoglobulin G (IgG) exhibits modular organization related to glycan epitope structure. The current study compares the glycan-specific IgG repertoires between different PAD entities. Distinct repertoire profiles with extensive qualitative glycan-recognition defects were observed, which are characterized by the common loss of Galα and GalNAc reactivity and disease-specific recognition of microbial antigens, self-antigens, and tumor-associated carbohydrate antigens. Antibody repertoire analysis may provide a useful tool to elucidate the degree and the clinical implications of immune system failure in individual patients.
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Perception of alcohol policies by consumers of unrecorded alcohol - An exploratory qualitative interview study with patients of alcohol treatment facilities in Russia
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21.11.2019 |
Neufeld M.
Wittchen H.
Ross L.
Ferreira-Borges C.
Rehm J.
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Substance Abuse: Treatment, Prevention, and Policy |
10.1186/s13011-019-0234-1 |
0 |
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© 2019 The Author(s). Background: Over the last decade Russia has introduced various policy measures to reduce alcohol consumption and alcohol-related harm at the population level. Several of these policies, such as higher pricing and taxation or restrictions of availability, may not work in the case of unrecorded alcohol consumption; they may encourage consumers to switch to unrecorded alcohol and even increase consumption. In the present qualitative interview study we explore the perception of the recently implemented alcohol policies by patients diagnosed with alcohol dependence in two Russian cities in the years 2013-2014 and shed light on possible entry-points to prevention. Methods: Semi-structured in-depth expert interviews were conducted with 25 patients of state-run drug and alcohol treatment centers in two Russian cities in 2013 and 2014. The interviews were analyzed using thematic content analysis. Results: All of the interviewed participants have consumed unrecorded at some point with the majority being regular consumers, mostly switching between recorded and unrecorded alcohol depending on the situation, as predominantly defined by available money and available sources of alcohol. Low price and high availability were reported as the main reasons for unrecorded consumption. Participants voiced a general mistrust of the recently implemented alcohol regulations and viewed them largely as ineffective. They expressed particular concerns over price increases and restriction of night sales of alcoholic beverages. Substantial shifts within the unrecorded alcohol market were reported, with a decreasing availability of home-made beverages in favor of alcohol surrogates in the form of non-beverage alcohol, medicinal and cosmetic compounds. At the same time consumption of home-made alcoholic beverages was seen as a strategy to avoid counterfeit alcohol, which was frequently reported for retail sale. Conclusions: Despite the alcohol policy changes in the last years in Russia, consumption of unrecorded alcohol remained common for people with alcohol dependence. Reduction of availability of unrecorded alcohol, first and foremost in the form of cheap surrogates, is urgently needed to reduce alcohol-related harm. Implementation of screening and brief interventions for excessive alcohol consumption in various contexts such as primary healthcare settings, trauma treatment services or the workplace could be another important measure targeting consumers of unrecorded alcohol.
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A novel guided surgery system with a sleeveless open frame structure: a retrospective clinical study on 38 partially edentulous patients with 1 year of follow-up
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21.11.2019 |
Mouhyi J.
Salama M.
Mangano F.
Mangano C.
Margiani B.
Admakin O.
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BMC oral health |
10.1186/s12903-019-0940-0 |
0 |
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BACKGROUND: This retrospective clinical study aims to present results of experience with a novel guided surgery system with a sleeveless, open-frame structure, in which the surgical handpiece (not the drills used for preparation) is guided. METHODS: This study was based on an evaluation of the records of partially edentulous patients who had been treated with a sleeveless open-frame guided surgery system (TWIN-Guide®, 2Ingis, Brussels, Belgium), between January 2015 and December 2017. Inclusion criteria were patients with good systemic/oral health and a minimum follow-up of 1 year. Exclusion criteria were patients who had been treated without a guide, or with a guide with sleeves, patients with systemic/oral diseases and who did not have a follow-up of 1 year. The main outcomes were surgical (fit and stability of the surgical guide, duration of the intervention, implant stability, and any intra-operative or immediate post-operative complication), biologic, and prosthetic. RESULTS: Thirty-eight patients (24 males, 14 females; mean age 56.5 ± 14.0 years) were included in the study. These patients had been treated with 110 implants inserted by means of 40 sleeveless, open-frame guides. With regard to fit and stability, 34 guides were excellent, 4 acceptable, and 2 inadequate for use. The mean duration of the intervention was 23.7 (± 6.7) minutes. Immediately after placement, 2 fixtures were not stable and had to be removed. Two patients experienced pain/swelling after surgery. The 108 surviving implants were restored with 36 single crowns and 32 fixed partial prostheses (24 two-unit and 8 three-unit bridges); these restorations survived until the 1-year follow-up, with a low incidence of biologic and prosthetic complications. CONCLUSIONS: Within the limits of this study, this novel guided surgery system with sleeveless, open frame-structure guides seems to be clinically reliable; further studies on a larger sample of patients are needed to confirm these outcomes.
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Evaluation of free and total fluoride concentration in mouthwashes via measurement with ion-selective electrode
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20.11.2019 |
Reshetnyak V.
Nesterova O.
Admakin O.
Dobrokhotov D.
Avertseva I.
Dostdar S.
Khakimova D.
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BMC Oral Health |
10.1186/s12903-019-0908-0 |
0 |
Ссылка
© 2019 The Author(s). Background: The aim of this study was to compare free fluoride concentration and total fluoride concentration in mouthwashes. Methods: Fluorine-containing mouthwashes from various companies and manufacturers (Colgate Total Plax Classic Mint®, Colgate-Palmolive, New York, USA; Colgate Total Plax Gentle Mint®, Colgate-Palmolive, New York, USA; Colgate Total Plax Fresh Mint®, Colgate-Palmolive, New York, USA; Oral B Advantage®, Procter&Gamble, Cincinnati, USA; Reach Fresh Mint®, Johnson&Johnson, New Brunswick, USA; Foramen®, Laboratorios Foramen, Guarnizo, Spain; Lacalut Sensitive®, Dr. THEISS, Homburg, Germany; Sensodyne®, GlaxoSmithKline, London, UK; Vesna F®, Vita, Saint Petersburg, Russia; Lacalut Fresh®, Dr. THEISS, Homburg, Germany) were selected as study objects. Fluoride measurements were carried out using the fluoride selective electrode. Results: Free fluoride:total fluoride ratio was more than 80% for six samples (Colgate Total Plax Gentle Mint® - 88%, Colgate Total Plax Fresh Mint® - 99%, Oral B Advantage® - 92%, Reach Fresh Mint® - 92 and 89% for the mouthwash of another batch, Lacalut Sensitive® - 94%) and less than 63% for three samples (Colgate Total Plax Classic Mint® - 56%, Foramen® - 62%, Vesna F® - 61%). Two samples had more than 70% and less than 80% of unbound fluoride, respectively (Sensodyne® - 77%, another batch of Oral B Advantage® mouthwash - 74%). Rinse containing sodium monofluorophosphate (Na2PO3F) (Vesna F®) had more than 50% of free fluoride, while the rinse containing amine fluoride (AmF) (Lacalut Sensitive®) had 94%. The difference in the free fluoride:total fluoride ratio can be explained by binding of fluoride ions by components contained in mouthwashes, such as coloring agents and polymeric compounds. The lowest concentration of free fluoride ions (0.000093 mol/L) was observed for aluminum fluoride (AlF3) rinse (Lacalut Fresh®), while the total fluoride amount was not determined due to possible generation of strong fluoride complexes. This implies that fluoride ions will not be uptaken by tooth tissue and may even be washed away from it, compromising the efficacy of mouthwashes. Conclusions: The differences in free fluoride: total fluoride ratio between analyzed mouthwashes reveal a need to develop a method for evaluation of free fluorides in mouthwashes for proper updating of national and international guidelines.
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Thanatochemistry at the crime scene: a microfluidic paper-based device for ammonium analysis in the vitreous humor
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20.11.2019 |
Musile G.
Agard Y.
De Palo E.
Shestakova K.
Bortolotti F.
Tagliaro F.
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Analytica Chimica Acta |
10.1016/j.aca.2019.07.033 |
0 |
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© 2019 Elsevier B.V. Most of the on-site approaches for inferring of the post-mortem interval are still based on observative data from the direct body inspection, whereas, objective and quantitative analyses, such as potassium in the vitreous humor, are require laboratory instrumentation and skilled personnel. The present paper presents a simple and low cost analytical method suitable for use at the crime scene for inferring the time since death. The method uses a microfluidic paper-based device (μPAD) for the determination of ammonium in the vitreous humor (VH) based on the selective interaction between the ammonium and the Nessler's reagent. The color change was measured in terms of “RGB distance” by using a simple and free smartphone application. The optimized device showed a limit of detection of 0.4 mmol L−1, with between days precision less than 9.3% expressed as relative standard deviation, and accuracy between days from 94.5% to 104.5%. The selectivity of the Nessler's reaction was tested towards the main vitreous humor compounds, and no significant interferences were found. This paper-based analytical device was successfully used for the determination of ammonium ion in VH samples from forensic autopsies. The results obtained with the proposed method, although for a limited number of cases (n = 25), showed a close correlation with the data obtained with an instrumental analysis based on capillary electrophoresis. Moreover, in order to make the evaluation of results as simple as possible, a direct correlation between the color intensity, expressed as RGB distance, and the post-mortem interval was studied and a significant correlation was found (R2 > 0.78). In conclusion, the present preliminary study showes that the proposed device could be an additional tool to the traditional methods for a more accurate, although still presumptive, estimation of the time of death directly at the crime scene.
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Interrogating Parkinson's disease associated redox targets: Potential application of CRISPR editing
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20.11.2019 |
Artyukhova M.
Tyurina Y.
Chu C.
Zharikova T.
Bayır H.
Kagan V.
Timashev P.
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Free Radical Biology and Medicine |
10.1016/j.freeradbiomed.2019.06.007 |
1 |
Ссылка
© 2019 Elsevier Inc. Loss of dopaminergic neurons in the substantia nigra is one of the pathogenic hallmarks of Parkinson's disease, yet the underlying molecular mechanisms remain enigmatic. While aberrant redox metabolism strongly associated with iron dysregulation and accumulation of dysfunctional mitochondria is considered as one of the major contributors to neurodegeneration and death of dopaminergic cells, the specific anomalies in the molecular machinery and pathways leading to the PD development and progression have not been identified. The high efficiency and relative simplicity of a new genome editing tool, CRISPR/Cas9, make its applications attractive for deciphering molecular changes driving PD-related impairments of redox metabolism and lipid peroxidation in relation to mishandling of iron, aggregation and oligomerization of alpha-synuclein and mitochondrial injury as well as in mechanisms of mitophagy and programs of regulated cell death (apoptosis and ferroptosis). These insights into the mechanisms of PD pathology may be used for the identification of new targets for therapeutic interventions and innovative approaches to genome editing, including CRISPR/Cas9.
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Functional connectivity studies in migraine: What have we learned?
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20.11.2019 |
Skorobogatykh K.
Van Hoogstraten W.
Degan D.
Prischepa A.
Savitskaya A.
Ileen B.
Bentivegna E.
Skiba I.
D'Acunto L.
Ferri L.
Sacco S.
Hansen J.
Amin F.
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Journal of Headache and Pain |
10.1186/s10194-019-1047-3 |
0 |
Ссылка
© 2019 The Author(s). Background: Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies. Methods: We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients. Results: We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies. Conclusion: Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.
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Gender difference in the association of dietary patterns and metabolic parameters with obesity in young and middle-aged adults with dyslipidemia and abnormal fasting plasma glucose in Taiwan
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16.11.2019 |
Lin L.
Hsu C.
Lee H.
Tinkov A.
Skalny A.
Wang W.
Chao J.
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Nutrition Journal |
10.1186/s12937-019-0503-x |
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© 2019 The Author(s). Background: The increasing prevalence of obesity has become a pandemic problem, and dietary patterns are one of the important factors causing obesity. Although the correlation between dietary patterns and obesity has been well explored, the gender difference on the association between dietary patterns and obesity remains unclear. The objective of this study examined whether gender difference existed in the relationship of dietary patterns with metabolic parameters and specific indices of adiposity among young and middle-aged adults with dyslipidemia and abnormal fasting plasma glucose (FPG) in Taiwan. Methods: A total of 14,087 subjects aged between 20 and 50 years with dyslipidemia and abnormal FPG were recruited in Taiwan between 2001 and 2010 for a cross-sectional study. Dyslipidemia was defined primarily according to the National Cholesterol Education Program Adult Treatment Panel III guidelines with minor modification. Abnormal FPG level was defined by the American Diabetes Association. Principal component analysis was conducted to identify dietary patterns. Multivariate logistic regression analysis was performed to evaluate the association of dietary patterns and metabolic parameters with different indices of adiposity including general obesity, central obesity, and high body fat, stratified by gender. Results: Two dietary patterns derived from principal component analysis were the prudent dietary pattern and the western dietary pattern. Both men and women in the highest quartile of the western dietary pattern had a significantly increased odds ratio of general obesity, central obesity, and high body fat. However, only male subjects in the higher quartiles of the prudent dietary pattern had a significantly decreased odds ratio of all indices of obesity. Both men and women with higher high-density lipoprotein cholesterol and total cholesterol levels had a significantly reduced odds ratio of general and central obesity, while those with higher triglycerides and FPG levels had a significantly increased odds ratio of general and central obesity. Higher low-density lipoprotein cholesterol level was significantly associated with an elevated odds ratio of high body fat, while higher total cholesterol level was significantly correlated with a reduced odds ratio of high body fat only in women. Conclusions: Gender difference exists in the association of dietary patterns and metabolic parameters with obesity and body fat in young and middle-aged adults with dyslipidemia and abnormal FPG in Taiwan.
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Nano-liquid chromatography for enantiomers separation of baclofen by using vancomycin silica stationary phase
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08.11.2019 |
D'Orazio G.
Fanali C.
Gentili A.
Tagliaro F.
Fanali S.
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Journal of Chromatography A |
10.1016/j.chroma.2019.07.012 |
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© 2019 Elsevier B.V. The chiral separation of baclofen (Bac) was obtained by nano-liquid chromatography tandem mass spectrometry (nano-LC–MS/MS) using a 100 μm I.D. fused silica capillary column packed with silica particles chemically modified with vancomycin. Various experimental parameters, such as composition (buffer concentration, water content, organic modifier) and pH of the mobile phase and sample solvent were investigated for method optimization. In order to increase the sensitivity an on-column focusing procedure was applied. Acceptable separation of Bac enantiomers was obtained in less than 11 min eluting in isocratic mode, with 90:10 MeOH/water (v/v) containing 10 mM ammonium acetate at pH 4.5. These optimized experimental conditions were applied to the analysis of human plasma samples spiked with racemic mixture of Bac. The use of a Buckypaper disc as sorbent membrane allows one to recover both enantiomers with yields ≥ 65%. The method was fully validated, following the identification criteria of the European Commission Decision 2002/657/EC.
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The Effect of Sample Bias and Experimental Artefacts on the Statistical Phylogenetic Analysis of Picornaviruses
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06.11.2019 |
Vakulenko Y.
Deviatkin A.
Lukashev A.
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Viruses |
10.3390/v11111032 |
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Statistical phylogenetic methods are a powerful tool for inferring the evolutionary history of viruses through time and space. The selection of mathematical models and analysis parameters has a major impact on the outcome, and has been relatively well-described in the literature. The preparation of a sequence dataset is less formalized, but its impact can be even more profound. This article used simulated datasets of enterovirus sequences to evaluate the effect of sample bias on picornavirus phylogenetic studies. Possible approaches to the reduction of large datasets and their potential for introducing additional artefacts were demonstrated. The most consistent results were obtained using "smart sampling", which reduced sequence subsets from large studies more than those from smaller ones in order to preserve the rare sequences in a dataset. The effect of sequences with technical or annotation errors in the Bayesian framework was also analyzed. Sequences with about 0.5% sequencing errors or incorrect isolation dates altered by just 5 years could be detected by various approaches, but the efficiency of identification depended upon sequence position in a phylogenetic tree. Even a single erroneous sequence could profoundly destabilize the whole analysis by increasing the variance of the inferred evolutionary parameters.
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Polymorphic modifications of novel cerium germanide Ce<inf>33.3</inf>Ir<inf>22.2</inf>Ge<inf>44.5</inf> (at.%)
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05.11.2019 |
Gribanov A.
Gribanova S.
Kaczorowski D.
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Journal of Alloys and Compounds |
10.1016/j.jallcom.2019.151695 |
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© 2019 Elsevier B.V. The formation of novel ternary cerium germanide with the chemical composition Ce33.3Ir22.2Ge44.5 (at.%) was established. As derived from powder X-ray diffraction data, the compound crystallizes with two polymorphic modifications. The high-temperature modification, established for as-cast alloy, possesses a tetragonal ThSi2-type structure and can be named as Ce(IrxGe1-x)2, x = 0.32. The low-temperature modification forms in the course of heat treatment at 1073 K, crystallizes with an orthorhombic structure of its own type and can be labeled as Ce3Ir2-xGe4+x, x = 0.02. Both structures belong to the AlB2 structural family and are closely related to each other. In both modifications, statistical mixtures of Ir and Ge atoms occupy same crystallographic sites. As found by means of magnetization measurements, the two structural variants of Ce33.3Ir22.2Ge44.5 (at.%) exhibit very similar magnetic properties. Both polymorphs are Curie-Weiss paramagnets with strong crystalline electric field features observed at low temperatures.
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