The potential role of emicizumab prophylaxis in severe von Willebrand disease
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01.03.2021 |
Barg A.A.
Avishai E.
Budnik I.
Brutman T.B.
Tamarin I.
Dardik R.
Bashari D.
Misgav M.
Lubetsky A.
Lalezari S.
Livnat T.
Kenet G.
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Blood Cells, Molecules, and Diseases |
10.1016/j.bcmd.2020.102530 |
0 |
Ссылка
© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.
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The potential role of emicizumab prophylaxis in severe von Willebrand disease
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01.03.2021 |
Barg A.A.
Avishai E.
Budnik I.
Brutman T.B.
Tamarin I.
Dardik R.
Bashari D.
Misgav M.
Lubetsky A.
Lalezari S.
Livnat T.
Kenet G.
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Blood Cells, Molecules, and Diseases |
10.1016/j.bcmd.2020.102530 |
0 |
Ссылка
© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.
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The distribution of conjunctival goblet cells in mice
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01.03.2021 |
Welss J.
Punchago N.
Feldt J.
Paulsen F.
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Annals of Anatomy |
10.1016/j.aanat.2020.151664 |
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Ссылка
© 2020 Purpose: To evaluate the density and distribution of conjunctival goblet cells in mice without clinical evidence of ocular surface diseases. Methods: Immediately after euthanasia of C57BL/6 wild-type mice, the eyes including eyelids were removed and fixed in paraformaldehyde. Entire eyeballs and eyelids were cut in series along the sagittal axis from nasal to temporal on a microtome and then stained with Periodic Acid-Schiff acid to visualize the goblet cells. At each section stained in this way, the conjunctival goblet cells of the entire upper and lower lid conjunctiva were counted by light microscopy. Additional (transmission electron microscopy) (TEM)-Analysis on ultrathin sections was performed to evaluate morphological differences. Results: The total number of conjunctival goblet cells differs markedly between individual animals. Categorisation into upper eyelid (UL) and lower eyelid (LL) and into regions (nasal, middle, temporal) revealed a significant increase of goblet cells from nasal to temporal in the UL and a significant decrease in the LL. Conclusion: The distribution of conjunctival goblet cells in mice differs considerably from humans and between individual animals. Therefore, precise selection of sampling and methods are needed to obtain comparable data. We recommend to use the middle region of the conjunctiva of UL/LL for goblet cell studies in mice. These findings are of particular interest for dry eye mouse models as well as pharmacological studies on mice with influence on their goblet cells.
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Arboviruses in the Astrakhan region of Russia for 2018 season: The development of multiplex PCR assays and analysis of mosquitoes, ticks, and human blood sera
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01.03.2021 |
Nikiforova M.A.
Kuznetsova N.A.
Shchetinin A.M.
Butenko A.M.
Kozlova A.A.
Larichev V.P.
Vakalova E.V.
Azarian A.R.
Rubalsky O.V.
Bashkina O.A.
Tkachuk A.P.
Gushchin V.A.
Gintsburg A.L.
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Infection, Genetics and Evolution |
10.1016/j.meegid.2021.104711 |
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© 2021 Elsevier B.V. The Astrakhan region of Russia is endemic for the number of arboviruses. In this paper, we describe the results of the detection of the list of neglected arboviruses in the Astrakhan region for the 2018 season. For the purpose of the study in-house PCR assays for detection of 18 arboviruses have been developed and validated using arboviruses obtained from Russian State Collection of Viruses. Pools of ticks (n = 463) and mosquitoes (n = 312) as well as 420 samples of human patients sera have been collected and analyzed. Using developed multiplex real-time PCR assays we were able to detect RNA of eight arboviruses (Crimean-Congo hemorrhagic fever virus, Dhori (Batken strain) virus, Batai virus, Tahyna virus, Uukuniemi virus, Inkoo virus, Sindbis virus and West Nile fever virus). All discovered viruses are capable of infecting humans causing fever and in some cases severe forms with hemorrhagic or neurologic symptoms. From PCR-positive samples, we were able to recover one isolate each of Dhori (Batken strain) virus and Crimean-Congo hemorrhagic fever virus which were further characterized by next-generation sequencing. The genomic sequences of identified Dhori (Batken strain) virus strain represent the most complete genome of Batken virus strain among previously reported.
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Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature
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01.03.2021 |
Giammattei L.
Starnoni D.
Benes V.
Froelich S.
Cossu G.
Borsotti F.
Májovsky M.
Sufianov A.A.
Fava A.
di Russo P.
Elbabaa S.K.
González-López P.
Messerer M.
Daniel R.T.
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World Neurosurgery |
10.1016/j.wneu.2020.12.042 |
0 |
Ссылка
© 2020 The Author(s) Objective: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. Methods: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. Results: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. Conclusions: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.
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Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature
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01.03.2021 |
Giammattei L.
Starnoni D.
Benes V.
Froelich S.
Cossu G.
Borsotti F.
Májovsky M.
Sufianov A.A.
Fava A.
di Russo P.
Elbabaa S.K.
González-López P.
Messerer M.
Daniel R.T.
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World Neurosurgery |
10.1016/j.wneu.2020.12.042 |
0 |
Ссылка
© 2020 The Author(s) Objective: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. Methods: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. Results: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. Conclusions: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.
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Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature
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01.03.2021 |
Giammattei L.
Starnoni D.
Benes V.
Froelich S.
Cossu G.
Borsotti F.
Májovsky M.
Sufianov A.A.
Fava A.
di Russo P.
Elbabaa S.K.
González-López P.
Messerer M.
Daniel R.T.
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World Neurosurgery |
10.1016/j.wneu.2020.12.042 |
0 |
Ссылка
© 2020 The Author(s) Objective: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. Methods: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. Results: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. Conclusions: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.
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Perioperative Dexmedetomidine Supplement Decreases Delirium Incidence After Adult Cardiac Surgery: A Randomized, Double-Blind, Controlled Study
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01.02.2021 |
Likhvantsev V.V.
Landoni G.
Grebenchikov O.A.
Ovezov A.M.
Skripkin Y.V.
Lembo R.
Gaevskiy D.I.
Tereshina A.A.
Yavorovskiy A.G.
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Journal of Cardiothoracic and Vascular Anesthesia |
10.1053/j.jvca.2020.02.035 |
0 |
Ссылка
© 2020 Elsevier Inc. Objective: Conflicting data exist on the effect of dexmedetomidine on delirium. For the present study, a randomized trial was performed to investigate the effect of perioperative dexmedetomidine on the rate of postoperative delirium after cardiac surgery. Design: A randomized controlled trial. Setting: University hospital. Participants: Patients (n = 169) undergoing elective cardiac surgery (coronary artery bypass graft surgery, valve surgery, or combined surgery) with cardiopulmonary bypass. Interventions: Patients received a sevoflurane-based general anesthesia and were randomly assigned 1:1 to receive a dexmedetomidine infusion that started in the operating room (0.7 μg/kg/h) and continued into the intensive care unit (0.4 μg/kg/h) or an equivolume infusion of placebo. Measurements and Main Results: A decrease in the rate of delirium in the dexmedetomidine group compared with the placebo group was demonstrated (6 of 84 [7.1%] v 16 of 85 [18.8%]; p = 0.02; odds ratio [OR] 0.33 [95% confidence interval {CI} 0.12-0.90]). Reduced intensive care unit and hospital lengths of stay also were observed (18 [18-22] hours v 22 [18-39] hours; p = 0.002 and 17 [7-20] days v 19 [8-21] days; p = 0.04, respectively). Mortality at 30 days was 2 (2.4%) in both groups. On multivariate analysis, only dexmedetomidine administration (OR 0.24 [95% CI 0.08-0.74]) and cardiopulmonary bypass time (OR 1.02 [95% CI 1.01-1.03] for increases of 1 min) were independent predictors of delirium development. Conclusions: Dexmedetomidine administered during and after general anesthesia for cardiac surgery with cardiopulmonary bypass decreased the rate of postoperative delirium and intensive care unit and hospital lengths of stay.
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A two-step microengineered system for high-density cell retention from bioreactors
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01.01.2021 |
Syed M.S.
Marquis C.
Taylor R.
Warkiani M.E.
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Separation and Purification Technology |
10.1016/j.seppur.2020.117610 |
0 |
Ссылка
© 2020 Elsevier B.V. Large-scale cell culture processes are required to produce biopharmaceuticals, cells for tissue engineering, and vaccine production while being effective in toxicity testing, gene therapy vector production for cancer research, and drug development. A growing trend in these industries, particularly for suspension cells, involves implementation of continuous cell perfusion processes, which require an aseptic, efficient, cost-effective, and reliable cell separation and retention scheme. Many cell separation techniques (membrane-based systems, lateral displacement devices, and acoustophoresis) have proven to be highly efficient, but suffer from issue of clogging and high cost, limiting their reliability, and thus, their overall feasibility. Some cell retention devices—those based on inertial microfluidics—offer high reliability (i.e., clog-free), but their efficiency reduces at higher cell concentrations. To overcome this apparent trade-off, we report the development of an integrated system consisting of two different membrane-less microfiltration techniques for cell separation from spent cell media. Although it could be adapted to numerous cell culture applications, this system was optimized and tested for suspension-adapted Chinese Hamster Ovary (CHO) cells. As the first step of the cell retention system, a miniaturised hydrocyclone was developed that could separate the cells with macroscopic volume processing rates (~200 mL/min). At this stage, up to 75% of the cells were isolated with minimal (<5%) change in the viability. The remaining cells passed through the overflow of the device and entered to a multiplexed spiral microchannel system, where more than 90% of the remaining cells were recovered, yielding an overall efficiency of up to 95%. The proposed integrated system is thus ideal for continuous and high throughput cell retention even at high cell concentrations (~80 million cells/mL), which is in range of current need in the bioprocessing industry.
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A two-step microengineered system for high-density cell retention from bioreactors
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01.01.2021 |
Syed M.S.
Marquis C.
Taylor R.
Warkiani M.E.
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Separation and Purification Technology |
10.1016/j.seppur.2020.117610 |
0 |
Ссылка
© 2020 Elsevier B.V. Large-scale cell culture processes are required to produce biopharmaceuticals, cells for tissue engineering, and vaccine production while being effective in toxicity testing, gene therapy vector production for cancer research, and drug development. A growing trend in these industries, particularly for suspension cells, involves implementation of continuous cell perfusion processes, which require an aseptic, efficient, cost-effective, and reliable cell separation and retention scheme. Many cell separation techniques (membrane-based systems, lateral displacement devices, and acoustophoresis) have proven to be highly efficient, but suffer from issue of clogging and high cost, limiting their reliability, and thus, their overall feasibility. Some cell retention devices—those based on inertial microfluidics—offer high reliability (i.e., clog-free), but their efficiency reduces at higher cell concentrations. To overcome this apparent trade-off, we report the development of an integrated system consisting of two different membrane-less microfiltration techniques for cell separation from spent cell media. Although it could be adapted to numerous cell culture applications, this system was optimized and tested for suspension-adapted Chinese Hamster Ovary (CHO) cells. As the first step of the cell retention system, a miniaturised hydrocyclone was developed that could separate the cells with macroscopic volume processing rates (~200 mL/min). At this stage, up to 75% of the cells were isolated with minimal (<5%) change in the viability. The remaining cells passed through the overflow of the device and entered to a multiplexed spiral microchannel system, where more than 90% of the remaining cells were recovered, yielding an overall efficiency of up to 95%. The proposed integrated system is thus ideal for continuous and high throughput cell retention even at high cell concentrations (~80 million cells/mL), which is in range of current need in the bioprocessing industry.
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Functional mechanisms for the development of acute respiratory viral infection
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01.01.2021 |
Medvedev I.N.
Bakulina E.D.
Rysakova O.G.
Garina E.V.
Dorontsev A.V.
Sibgatulina F.R.
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International Journal of Pharmaceutical Research |
10.31838/ijpr/2021.13.01.057 |
0 |
Ссылка
© 2020, Advanced Scientific Research. All rights reserved. In the modern world, acute respiratory viral infections are a widespread and socially significant disease. Having the similarity of structure, epidemiology and strong tropism to the respiratory tract, each causative agent of acute respiratory viral infection has its own characteristics. The most severe course with complications is characteristic of influenza. More than 200 viruses are known to cause acute respiratory viral infections. Their diversity is very great. This creates a situation when a person, having been ill with a disease caused by one virus, can immediately become infected with other viruses of this group and get sick again. For a year in the world, for an adult, 3-4 cases of the disease of acute respiratory viral infection occur. A child suffers from this infection 6-9 times during the year. 3.9 million deaths worldwide are associated with acute respiratory viral infections each year. Due to the enormous social significance of acute respiratory viral infection, the World Health Organization has launched the Battle against Respiratory Viruses initiative to combat it. Her prerequisites were problems with the treatment and prevention of acute respiratory viral infection. It is aimed at improving diagnostic methods to differentiate viral and bacterial infections at the earliest stages of the disease, developing effective antiviral drugs for the most common viruses and safe and effective stimulants of defense mechanisms in the body. It becomes clear that acute respiratory viral infections are a diverse group of infectious diseases of the respiratory tract that have similar developmental mechanisms, epidemiological and clinical characteristics. Given that these diseases have a high contagiousness, rapid spread, a significant number of complications, especially among people at risk, they require serious and lengthy research.
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Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19
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01.01.2021 |
Avdeev S.N.
Yaroshetskiy A.I.
Tsareva N.A.
Merzhoeva Z.M.
Trushenko N.V.
Nekludova G.V.
Chikina S.Y.
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American Journal of Emergency Medicine |
10.1016/j.ajem.2020.09.075 |
0 |
Ссылка
© 2020 Elsevier Inc. Aim: Noninvasive ventilation (NIV) is known to reduce intubation in patients with acute hypoxemic respiratory failure (AHRF). We aimed to assess the outcomes of NIV application in COVID-19 patients with AHRF. Materials & methods: In this retrospective cohort study, patients with confirmed diagnosis of COVID-19 and AHRF receiving NIV in general wards were recruited from two university-affiliated hospitals. Demographic, clinical, and laboratory data were recorded at admission. The failure of NIV was defined as intubation or death during the hospital stay. Results: Between April 8 and June 10, 2020, 61 patients were enrolled into the final cohort. NIV was successful in 44 out of 61 patients (72.1%), 17 patients who failed NIV therapy were intubated, and among them 15 died. Overall mortality rate was 24.6%. Patients who failed NIV were older, and had higher respiratory rate, PaCO2, D-dimer levels before NIV and higher minute ventilation and ventilatory ratio on the 1-st day of NIV. No healthcare workers were infected with SARS-CoV-2 during the study period. Conclusions: NIV is feasible in patients with COVID-19 and AHRF outside the intensive care unit, and it can be considered as a valuable option for the management of AHRF in these patients.
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Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19
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01.01.2021 |
Avdeev S.N.
Yaroshetskiy A.I.
Tsareva N.A.
Merzhoeva Z.M.
Trushenko N.V.
Nekludova G.V.
Chikina S.Y.
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American Journal of Emergency Medicine |
10.1016/j.ajem.2020.09.075 |
0 |
Ссылка
© 2020 Elsevier Inc. Aim: Noninvasive ventilation (NIV) is known to reduce intubation in patients with acute hypoxemic respiratory failure (AHRF). We aimed to assess the outcomes of NIV application in COVID-19 patients with AHRF. Materials & methods: In this retrospective cohort study, patients with confirmed diagnosis of COVID-19 and AHRF receiving NIV in general wards were recruited from two university-affiliated hospitals. Demographic, clinical, and laboratory data were recorded at admission. The failure of NIV was defined as intubation or death during the hospital stay. Results: Between April 8 and June 10, 2020, 61 patients were enrolled into the final cohort. NIV was successful in 44 out of 61 patients (72.1%), 17 patients who failed NIV therapy were intubated, and among them 15 died. Overall mortality rate was 24.6%. Patients who failed NIV were older, and had higher respiratory rate, PaCO2, D-dimer levels before NIV and higher minute ventilation and ventilatory ratio on the 1-st day of NIV. No healthcare workers were infected with SARS-CoV-2 during the study period. Conclusions: NIV is feasible in patients with COVID-19 and AHRF outside the intensive care unit, and it can be considered as a valuable option for the management of AHRF in these patients.
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Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
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01.12.2020 |
Kleine-Weber H.
Schroeder S.
Krüger N.
Prokscha A.
Naim H.
Müller M.
Drosten C.
Pöhlmann S.
Hoffmann M.
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Emerging microbes & infections |
10.1080/22221751.2020.1713705 |
0 |
Ссылка
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.
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Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
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01.12.2020 |
Kleine-Weber H.
Schroeder S.
Krüger N.
Prokscha A.
Naim H.
Müller M.
Drosten C.
Pöhlmann S.
Hoffmann M.
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Emerging microbes & infections |
10.1080/22221751.2020.1713705 |
0 |
Ссылка
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.
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Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
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01.12.2020 |
Kleine-Weber H.
Schroeder S.
Krüger N.
Prokscha A.
Naim H.
Müller M.
Drosten C.
Pöhlmann S.
Hoffmann M.
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Emerging microbes & infections |
10.1080/22221751.2020.1713705 |
0 |
Ссылка
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.
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Cellular effects and clinical implications of SLC2A3 copy number variation
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01.12.2020 |
Ziegler G.C.
Almos P.
McNeill R.V.
Jansch C.
Lesch K.P.
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Journal of Cellular Physiology |
10.1002/jcp.29753 |
2 |
Ссылка
© 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC SLC2A3 encodes the predominantly neuronal glucose transporter 3 (GLUT3), which facilitates diffusion of glucose across plasma membranes. The human brain depends on a steady glucose supply for ATP generation, which consequently fuels critical biochemical processes, such as axonal transport and neurotransmitter release. Besides its role in the central nervous system, GLUT3 is also expressed in nonneural organs, such as the heart and white blood cells, where it is equally involved in energy metabolism. In cancer cells, GLUT3 overexpression contributes to the Warburg effect by answering the cell's increased glycolytic demands. The SLC2A3 gene locus at chromosome 12p13.31 is unstable and prone to non-allelic homologous recombination events, generating multiple copy number variants (CNVs) of SLC2A3 which account for alterations in SLC2A3 expression. Recent associations of SLC2A3 CNVs with different clinical phenotypes warrant investigation of the potential influence of these structural variants on pathomechanisms of neuropsychiatric, cardiovascular, and immune diseases. In this review, we accumulate and discuss the evidence how SLC2A3 gene dosage may exert diverse protective or detrimental effects depending on the pathological condition. Cellular states which lead to increased energetic demand, such as organ development, proliferation, and cellular degeneration, appear particularly susceptible to alterations in SLC2A3 copy number. We conclude that better understanding of the impact of SLC2A3 variation on disease etiology may potentially provide novel therapeutic approaches specifically targeting this GLUT.
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Health of refugees and migrants from former Soviet Union countries in the Russian Federation: a narrative review
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01.12.2020 |
Bakunina N.
Gil A.
Polushkin V.
Sergeev B.
Flores M.
Toskin I.
Madyanova V.
Khalfin R.
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International Journal for Equity in Health |
10.1186/s12939-020-01279-0 |
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© 2020, The Author(s). This narrative review was conducted to synthesize and summarize available up-to-date evidence on current health status, including both non-communicable diseases and infectious diseases, of migrants and refugees from the former Soviet Union countries in the Russian Federation. Epidemiological and sociological studies with one or more determinants of the health, as well as relevant qualitative studies characterizing risk factors, well-being indicators, and lifestyles of migrants and refugees from the former Soviet Union countries in Russia published from 2004 to 2019 in Russian and English languages were included in the review. Despite significant limitations of the available research literature in the field, some patterns in migrants’ health in Russia and issues that need to be addressed were identified. In particular, the syndemic epidemics of communicable and non-communicable diseases, additively increasing negative health consequences, including cardiovascular diseases and chronic digestive system diseases, high rates of sexually transmitted infections and HIV, respiratory diseases and a growing percentage of new tuberculosis cases among migrants from the former Soviet Union countries are all of great concern. Possibly, the burden of these co-occurring morbidities is linked to commonly reported issues among this population group, such as poor nutrition and living conditions, high prevalence of unskilled manual labour, non-compliance with sanitary norms, lack of basic vaccinations, lack of basic knowledge about safe sexual practices and risky sexual behaviour, low healthcare seeking behaviour and limited access to health care. Importantly, these findings may urge the government to increase efforts and promote international collaboration in combating the threat of infectious diseases. Additionally, it was found that migrants had higher levels of anxiety and post-traumatic stress disorder, and those who stayed in the receiving country 5 years or more had a higher level of somatic pathology than those whose stay was less than 5 years. In order to ensure an adequate health system response and fulfil the main Universal Health Coverage principle of “leaving no one behind”, a robust monitoring system of the health status of refugees and migrants and an integrated legal framework for the standardized and more inclusive routine care for this population in Russia is urgently needed.
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Poly(3-hydroxybutyrate)/hydroxyapatite/alginate scaffolds seeded with mesenchymal stem cells enhance the regeneration of critical-sized bone defect
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01.09.2020 |
Volkov A.V.
Muraev A.A.
Zharkova I.I.
Voinova V.V.
Akoulina E.A.
Zhuikov V.A.
Khaydapova D.D.
Chesnokova D.V.
Menshikh K.A.
Dudun A.A.
Makhina T.K.
Bonartseva G.A.
Asfarov T.F.
Stamboliev I.A.
Gazhva Y.V.
Ryabova V.M.
Zlatev L.H.
Ivanov S.Y.
Shaitan K.V.
Bonartsev A.P.
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Materials Science and Engineering C |
10.1016/j.msec.2020.110991 |
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© 2020 Elsevier B.V. A critical-sized calvarial defect in rats is employed to reveal the osteoinductive properties of biomaterials. In this study, we investigate the osteogenic efficiency of hybrid scaffolds based on composites of a biodegradable and biocompatible polymer, poly(3-hydroxybutyrate) (PHB) with hydroxyapatite (HA) filled with alginate (ALG) hydrogel containing mesenchymal stem cells (MSCs) on the regeneration of the critical-sized radial defect of the parietal bone in rats. The scaffolds based on PHB and PHB/HA with desired shapes were prepared by two-stage salt leaching technique using a mold obtained by three-dimensional printing. To obtain PHB/HA/ALG/MSC scaffolds seeded with MSCs, the scaffolds were filled with ALG hydrogel containing MSCs; acellular PHB/ALG and PHB/ALG filled with empty ALG hydrogel were prepared for comparison. The produced scaffolds have high porosity and irregular interconnected pore structure. PHB/HA scaffolds supported MSC growth and induced cell osteogenic differentiation in a regular medium in vitro that was manifested by an increase in ALP activity and expression of the CD45 phenotype marker. The data of computed tomography and histological studies showed 94% and 92%, respectively, regeneration of critical-sized calvarial bone defect in vivo at 28th day after implantation of MSC-seeded PHB/HA/ALG/MSC scaffolds with 3.6 times higher formation of the main amount of bone tissue at 22–28 days in comparison with acellular PHB/HA/ALG scaffolds that was shown at the first time by fluorescent microscopy using the original technique of intraperitoneal administration of fluorescent dyes to living postoperative rats. The obtained in vivo results can be associated with the MSC-friendly microstructure and in vitro osteogenic properties of PHB/HA base-scaffolds. Thus, the obtained data demonstrate the potential of MSCs encapsulated in the bioactive biopolymer/mineral/hydrogel scaffold to improve the bone regeneration process in critical-sized bone defects.
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Enhanced morphological transformation of human lung epithelial cells by continuous exposure to cellulose nanocrystals
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01.07.2020 |
Kisin E.R.
Yanamala N.
Rodin D.
Menas A.
Farcas M.
Russo M.
Guppi S.
Khaliullin T.O.
Iavicoli I.
Harper M.
Star A.
Kagan V.E.
Shvedova A.A.
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Chemosphere |
10.1016/j.chemosphere.2020.126170 |
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© 2020 Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.
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