174 results on '"T. Andreeva"'
Search Results
102. [Study of some veterinary drug forms containing 5-nitrofuran derivatives (furagin, furazolidone, furacillin)]
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A T, Andreeva, I S, Azhgikhin, and Ia A, Vetra
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Veterinary Medicine ,Nitrofurans ,Nitrofurazone ,Suppositories ,Animals ,Furazolidone ,Cattle ,Rabbits ,Absorption - Published
- 1973
103. Dose-dependent genotoxicity of ammonia-modified graphene oxide particles in lung cancer cells.
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K Hristova-Panusheva, M Keremidarska-Markova, T Andreeva, G Speranza, D Wang, M Georgieva, G Miloshev, and N Krasteva
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- 2019
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104. Anglo-American 'special relationship' under the government of David Cameron
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T. Andreeva
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Economics and Econometrics ,Government ,Special Relationship ,Political science ,Political Science and International Relations ,Economic history - Abstract
The article is devoted to the Anglo-American "special relationship" maintaining under two U.S. governments of Barak Obama and two Britain's governments – the coalition government of David Cameron-Nicholas Clegg and the conservative government of D. Cameron. The paper covers the evolution of the bilateral relationship from worsening to improving, which came into being amid the American economic and military resources overheating due to the shift of the U.S. political interest from Europe to the Pacific region and overstretch of American military communications as a result. The author scrutinizes only two main fields of this "special relationship": political and military cooperation. International events and political steps of both countries have rescued their relations from the collapse and have boosted them. The article deals with the role of such international crises as wars in Afghanistan, Iraq, Libya, Syria, combating the Islamic State (Islamic jihadists) and the Ukrainian crisis in preserving the speciality of Anglo-American relations. The author comes to a conclusion that Britain's participation in military operations around the world as the main partner of the U.S. is the main reason for improving the bilateral relationship. The attention is paid to the trends in cooperation making the relationship special, such as nuclear, sea and intelligence cooperation. The partnership between two countries in NATO is also highlighted. The author regards the movement for Scottish secession from the United Kingdom as one of political tendencies in the British society which bring uncertainties to Britain–U.S. relations. Special attention is paid to another political trend in the British society – the movement for Britain's exit from the European Union, which is a real threat for Anglo-American "special relationship", because it can ruin its traditional pillar – the bridge between the U.S. and Europe. The author tries to answer the question about perspectives of Anglo-American "special relationship" under the Cameron's government.
105. Global energy confinement in the initial limiter configuration of Wendelstein 7-X.
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G. Fuchert, S.A. Bozhenkov, N. Pablant, K. Rahbarnia, Y. Turkin, A. Alonso, T. Andreeva, C.D. Beidler, M. Beurskens, A. Dinklage, J. Geiger, M. Hirsch, U. Höfel, J. Knauer, A. Langenberg, H.P. Laqua, H. Niemann, E. Pasch, T. Sunn Pedersen, and T. Stange
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PLASMA confinement ,FUSION reactor divertors ,FUSION reactor limiters ,STELLARATORS ,PLASMA density - Abstract
Global confinement properties of the limiter plasmas of the first operational campaign of W7-X are investigated with special focus on the energy confinement and possible operational limits. The energy confinement time was found to be close to expectations from the empirical ISS04 scaling for stellarators. Absolute values up to were achieved. This can be considered as a great success for the initial operation of the device. However, a clear degradation of the performance was observed when radiative losses became significant, which was typically the case at low heating power. While a significant improvement of the plasma purity is expected during divertor operation, the presented results underline the importance of the impurity dynamics for the development of high-performance steady-state scenarios in W7-X. Furthermore, comparisons of the global performance properties with neoclassical transport modeling are presented. These studies are not yet fully conclusive, which could indicate that anomalous transport may have played an essential role in the low-density OP1.1 plasmas. [ABSTRACT FROM AUTHOR]
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- 2018
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106. Diamagnetic energy measurement during the first operational phase at the Wendelstein 7-X stellarator.
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K. Rahbarnia, H. Thomsen, U. Neuner, J. Schilling, J. Geiger, G. Fuchert, T. Andreeva, M. Endler, D. Hathiramani, T. Bluhm, M. Zilker, B.b. Carvalho, A. Werner, and Team, Wendelstein 7-X.
- Subjects
DIAMAGNETIC materials ,STELLARATORS ,MAGNETIC flux ,THOMSON scattering ,X-ray imaging - Abstract
The magnetic diagnostic system at the Wendelstein 7-X stellarator includes three diamagnetic loops to measure magnetic flux changes in the plasma. Their signals are directly related to the plasma energy. The diagnostic design with respect to materials, component cooling and data acquisition is built to be fully steady-state capable within the harsh environment of a fusion plasma device. During the first operational phase, two diamagnetic loops have been put into operation, each of them close to one of the up-down symmetric main planes of the plasma column with a bean-shaped and triangular-shaped cross-section, respectively. Both loops measured reliable energies in accordance to theoretical expectations. The triangular-shaped diamagnetic loop is equipped with four compensation coils. They are used to compensate errors during the energy measurement due to small fluctuations of externally driven currents in the main superconducting magnetic field coils and eddy currents in the adjacent vacuum vessel and thereby increase the time-resolution allowing to measure fast changes of the plasma energy. The diamagnetic flux measurements agree well with corresponding estimations of diamagnetic signals using three-dimensional Biot–Savart calculations. A consistency check for the diamagnetic energy is performed by a reconstruction of the associated Pfirsch–Schlüter current distribution and a comparison of predicted signals with measurements of an arrangement of eight plasma encircling Rogowski coil segments. Additionally, the measured diamagnetic energy is compared to kinetic energy calculations based on density and temperature measurements performed by the Thomson scattering diagnostic and the x-ray imaging crystal spectrometer diagnostic. The resulting energy confinement times are similar to predictions of empirical scaling laws, like ISS04. For upcoming operational periods of Wendelstein 7-X, the diamagnetic energy measurement will be used to generate an interlock signal, which will turn off the main plasma heating systems in case of a sudden, unwanted plasma collapse. [ABSTRACT FROM AUTHOR]
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- 2018
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107. Confinement in Wendelstein 7-X limiter plasmas.
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M. Hirsch, A. Dinklage, A. Alonso, G. Fuchert, S. Bozhenkov, U. Höfel, T. Andreeva, J. Baldzuhn, M. Beurskens, H.-S. Bosch, C.D. Beidler, C. Biedermann, E. Blanco, R. Brakel, R. Burhenn, B. Buttenschön, A. Cappa, A. Czarnecka, M. Endler, and T. Estrada
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PLASMA confinement ,PLASMA gases ,STELLARATORS ,ELECTRONS ,PLASMA currents - Abstract
Observations on confinement in the first experimental campaign on the optimized Stellarator Wendelstein 7-X are summarized. In this phase W7-X was equipped with five inboard limiters only and thus the discharge length restricted to avoid local overheating. Stationary plasmas are limited to low densities <2–3 · 10
19 m−3 . With the available 4.3 MW ECR Heating core Te ~ 8 keV, Ti ~ 1–2 keV are achieved routinely resulting in energy confinement time τE between 80 ms to 150 ms. For these conditions the plasmas show characteristics of core electron root confinement with peaked Te -profiles and positive Er up to about half of the minor radius. Profiles and plasma currents respond to on- and off-axis heating and co- and counter ECCD respectively. [ABSTRACT FROM AUTHOR]- Published
- 2017
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108. Plans for the first plasma operation of Wendelstein 7-X.
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T. Sunn Pedersen, T. Andreeva, H.-S. Bosch, S. Bozhenkov, F. Effenberg, M. Endler, Y. Feng, D.A. Gates, J. Geiger, D. Hartmann, H. Hölbe, M. Jakubowski, R. König, H.P. Laqua, S. Lazerson, M. Otte, M. Preynas, O. Schmitz, T. Stange, and Y. Turkin
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PLASMA physics , *STELLARATORS , *PLASMA confinement devices , *FUSION reactor limiters , *FUSION reactor materials - Abstract
Wendelstein 7-X (W7-X) is currently under commissioning in preparation for its initial plasma operation phase, operation phase 1.1 (OP1.1). This first phase serves primarily to provide an integral commissioning of all major systems needed for plasma operation, as well as systems, such as diagnostics, that need plasma operation to verify their foreseen functions. In OP1.1, W7-X will have a reduced set of in-vessel components. In particular, five graphite limiter stripes replace the later foreseen divertor. This paper describes the expected machine capabilities in OP1.1, as well as a selection of physics topics that can be addressed in OP1.1, despite the simplified configuration and the reduced machine capabilities. Physics topics include the verification and adjustment of the magnetic topology, the testing of the foreseen plasma start-up scenarios and the feed-forward control of plasma density and temperature evolution, as well as more advanced topics such as scrape-off layer (SOL) studies at short connection lengths and transport studies. Plasma operation in OP1.1 will primarily be performed in helium, with a hydrogen plasma phase at the end. [ABSTRACT FROM AUTHOR]
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- 2015
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109. Tracking of the magnet system geometry during Wendelstein 7-X construction to achieve the designed magnetic field.
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T. Andreeva, T. Bräuer, V. Bykov, K. Egorov, M. Endler, J. Fellinger, J. Kißlinger, M. Köppen, and F. Schauer
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MAGNETS , *MAGNETIC fields , *STELLARATORS , *MANUFACTURING processes - Abstract
Wendelstein 7-X, currently under commissioning at the Max-Planck-Institut für Plasmaphysik in Greifswald, Germany, is a modular advanced stellarator, combining the modular coil concept with optimized properties of the plasma. Most of the envisaged magnetic configurations of the machine are rather sensitive to symmetry breaking perturbations which are the consequence of unavoidable manufacturing and assembly tolerances. This overview describes the successive tracking of the Wendelstein 7-X magnet system geometry starting from the manufacturing of the winding packs up to the modelling of the influence of operation loads. The deviations found were used to calculate the resulting error fields and to compare them with the compensation capacity of the trim coils. [ABSTRACT FROM AUTHOR]
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- 2015
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110. Psychic trauma and mental characteristics of patients with multiple sclerosis as predictors of post-traumatic stress disorder and targets for psychotherapy
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M. T. Andreeva, T. A. Karavaeva, and I. V. Kalinin
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psychotherapy targets ,comorbid mental disorder ,post-traumatic stress disorder (ptsd) ,resilience ,stress tolerance ,Psychiatry ,RC435-571 - Abstract
The article describes the psychological characteristics of the personality of patients with multiple sclerosis (MS), which can be identified as the main targets of psychotherapy for comorbid post-traumatic stress disorder (PTSD). A total of 127 patients with MS were examined, of which 61 patients had symptoms of PTSD that developed in connection with the underlying disease. The control group included 67 MS patients resistant to stress. To assess the structure of personality and psyche, Ammon’s I-structural test was used (G. Ammon, 1976, adaptation by Yu. Ya. Tupitsin, V. V. Bocharov, T. V. Alkhazova, E. V. Brodskaya, 1998). To determine the level of resilience, which is defined as the patient’s ability to navigate in a crisis situation and get out of stress with minimal damage to mental and physical health, D.A. Leontiev (D.A. Leontiev, E.I. Rasskazova, 2006).As a result of the study, it was revealed that patients of the main group have significantly lower scores on all scales of the resilience questionnaire («involvement», «control», «risk acceptance»). At the same time, patients with PTSD are characterized by a higher level of destructive and deficient manifestations of selffunctions on the Ammon scale, in contrast to patients in the control group. Decreased characteristics of hardiness, the predominance of deficient and destructive personality structures are predictors of the onset of post-traumatic stress disorder in patients with MS. The revealed psychological phenomena should be the targets of psychoprophylactic and psychotherapeutic influence in complex programs for the treatment and rehabilitation of these patients.
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- 2022
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111. Attitude towards the disease and quality of life of patients with multiple sclerosis as a target of personalized psychotherapy for PTSD
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M. T. Andreeva, T. A. Karavaeva, and I. V. Kalinin
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post-traumatic stress disorder ,multiple sclerosis ,quality of life ,internal picture of the disease ,attitude to the disease ,anxiety about progression ,targets of psychotherapy ,Psychiatry ,RC435-571 - Abstract
Attitude towards the disease and quality of life of patients with multiple sclerosis as a target of personalized psychotherapy for PTSDA chronic, progressive, potentially disabling disease with a poor prognosis can trigger the development of post-traumatic stress disorder (PTSD). The article presents the results of a survey of 127 patients with multiple sclerosis (MS), of which 61 patients had PTSD symptoms that developed in connection with the underlying disease were verified. The control group included 67 patients with MS who were resistant to stress. To fulfill the objectives of the study, all patients underwent a thorough collection of anamnestic information. To study the structure of the internal picture of the disease, we used a test technique aimed at diagnosing the type of attitude toward the disease (TOBOL). The study of QOL indicators was carried out using the SF-36 questionnaire.To assess the cognitive, emotional and behavioral aspects of anxiety about progression, the following questionnaires were used: “A short questionnaire for assessing the fear of disease progression” A. Mehnert, P. Herschbach, P. Berg (2006), adapted by N.А. Sirota, D.V. Moskovchenko (2014) and “Questionnaire of cognitive ideas about the disease” A. Evers, F. Kraaimaat (1998), adapted by N.A. Sirota, D.V. Moskovchenko (2014). As a result of the study, it was revealed that the patients of the main group have significantly lower scores of both physical and mental functioning when assessing the quality of life. At the same time, patients with PTSD are characterized by a higher intensity of anxiety about progression, negative thinking, and emotional reactions associated with the disease. An inadequate internal picture of the disease, characterized by the presence of mental maladjustment due to the disease, prevails in the group of patients with PTSD. All of these factors can be predictors of the development of PTSD. It is necessary to conduct further studies of the psychological characteristics of this group of patients in order to identify the targets of psychotherapeutic influence.
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- 2021
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112. Identification and characteristics of post-traumatic stress disorder in patients with multiple sclerosis
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M. T. Andreeva and T. A. Karavaeva
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post-traumatic stress disorder ,multiple sclerosis ,dissociation ,adaptive disorder ,Psychiatry ,RC435-571 - Abstract
The fourth edition of the Diagnostic and Statistical Manual on Mental Disorders (DSM-IV) recognizes the existence of a disease as a potential life-threatening stressor capable of causing post-traumatic stress disorder (PTSD). This research is one of the first works dedicated to the study of PTSD in patients diagnosed with «multiple sclerosis» (RS). A total of 724 complete sample patients were screened for outpatient treatment at the «City MS Center» in Saint Petersburg. According to the results of the screening survey and the expert clinical interview for the verification of the diagnosis of PTSD, the clinic—psychopathological signs sufficient for the diagnosis of PTSD have been identified in 61 patients, which is 8.4% of the total number of screened patients. The presence of PTSD is confirmed by high indices of sub-scales «avoidance», «intrusion», «physiological excitability» on the WOVTS scale, as well as higher indicators of dissociation level compared to control group. The lack of correlation between PTSD and the duration of RS, the degree of disability of patients, as well as socio-demographic data was found. Thus, the development of PTSD is more related to the premorbid personality characteristics than to the characteristics of the disease. These findings suggest that RS may have PTSD-type reactions. Further studies of the psychological characteristics of this group of patients are needed to identify the targets for psychotherapy.
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- 2020
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113. Associated Psychological Disorders and Impairment of Emotional Regulation among Patients with Multiple Sclerosis
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M. T. Andreeva and T. A. Karavaeva
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multiple sclerosis ,comorbid psychological disorders ,bipolar disorder ,depression ,anxiety disorders ,posttraumatic stress disorder ,Psychiatry ,RC435-571 - Abstract
The review of data from the available literature cites the results of studies of psychological disorders comorbid to multiple sclerosis and highlights scientific papers detailing domestic and foreign research. The high prevalence of affective and adaptive impairment is linked both to the neurophysiological particularities of this chronic, progressive, neurodegenerative illness and to psychological factors — individual personality traits and the attitude of those afflicted to their illness, to the change in their social functioning and to their prognosis. It is demonstrated that patients with multiple sclerosis have a significantly higher frequency of depressive and anxiety disorders than the general population, which suggests the need for an integrated, personalized approach to people with this illness.
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- 2020
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114. Primary hyperparathyroidism: clinical forms and their features. Retrospective study
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Liubov G. Yanevskaya, Tatiana L. Karonova, Ilya V. Sleptsov, Marina E. Boriskova, Aluza R. Bakhtiyarova, Ekaterina V. Ivanova, Karina A. Pogosian, Uliana V. Farafonova, Alena T. Andreeva, Uliana A. Tsoi, and Elena N. Grineva
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primary hyperparathyroidism ,parathyroid neoplasms ,parathyroid hormone ,vitamin d ,hypercalcemia ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background: Primary hyperparathyroidism (PHPT) is a disease characterized by autonomous production of parathyroid hormone (PTH) from one or more parathyroid glands. Over the past 50 years asymptomatic form of the disease have become more prevalent in developed countries. Aims: To evaluate the clinical forms of PHPT presented in recent years and to specify the clinical and laboratory features in patients with symptomatic and asymptomatic forms of the disease. Materials and methods: We reviewed medical records of 449 patients admitted to three Medical Centers (Saint-Petersburg, Russia) between 20112018. Anamnesis, anthropometric data, laboratory (PTH, serum total calcium and ionized calcium, phosphorus, alkaline phosphatase, 24-h calciuria level, 25(OH)D) and instrumental (ultrasonography, scintigraphy, CT/MRI scan, DXA) tests were analyzed. Results: Patients average age was 59 years, with 93.1% women, and an F:M ratio of 13.5:1. Symptomatic form ofPHPT was identified in 310 patients (69%), while 139 were asymptomatic. 4.2% of patients had PHPT as part ofMEN syndrome. Almost half of the male population had urolithiasis and 45% of women had osteoporosis. Cardiovascular diseases were present in 64.4% of cases. 25(OH)D level was determined only in 20% of cases and was higher in asymptomatic patients (32.2 18.6 ng/ml, p = 0.003). Normocalcemic form of PHPT was diagnosed in37 patients (8.2%) and was characterized not only by normocalcemia and lower PHT level, but also by smaller adenoma size (p = 0.01) and hypocalcemic syndrome after surgery. Conclusions: Study results showed that symptomatic PHPT is more prevalent in the Russian population, that there are gender distinctions affecting the clinical presentation, and that the frequency of cardiovascular disease is high in this patient population. PHPT as part of MEN syndrome was detected in 4.2% of cases and required molecular genetic testing. Normocalcemic form of PHPT with postoperative hypocalcemia was present in every fourth patient. Rare determination of 25(OH)D level imposes the need of mandatory assessment of vitamin D supplementation and the reduction of its deficiency as part of the preoperative preparation of PHPT patients.
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- 2019
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115. Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19
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Tatiana L. Karonova, Alena T. Andreeva, Ksenia A. Golovatuk, Ekaterina S. Bykova, Anna V. Simanenkova, Maria A. Vashukova, William B. Grant, and Evgeny V. Shlyakhto
- Subjects
vitamin D deficiency ,25(OH)D ,obesity ,COVID-19 ,Nutrition. Foods and food supply ,TX341-641 - Abstract
We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21–93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.
- Published
- 2021
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116. UROVEN' OBESPEChENNOSTI VITAMINOM D U ZhITELEY SEVERO-ZAPADNOGO REGIONA RF I ZNAChENIE DEFITsITA VITAMINA D DLYa ZDOROV'Ya
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T L KARONOVA, E P MIKhEEVA, I L NIKITINA, OD BELYaEVA, A M TODIEVA, P V POPOVA, A T ANDREEVA, P Yu GLOBA, I S BELETsKAYa, E Yu VASIL'EVA, E N GRINEVA, and O V GALKINA
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Osteopathy ,RZ301-397.5 - Abstract
Российская Федерация в силу географического расположения и экономических особенностей имеет все предпосылки для развития недостатка и дефицита витамина D. Цель исследования. Оценить уровень 25(OH)D) крови у жителей Северо-Западного региона РФ для изучения распространенности дефицита витамина D и его вклада в здоровье. Материал и методы. В исследование включено 1690 человек (1349 в возрасте 18-75 лет, включая 221 беременную и 120 детей/подростков в возрасте 3-17 лет). Уровень 25(OH)D крови оценивался хемилюминесцентным методом (AbbottArchitect 8000, USA), у беременных исследование проводилось на 8-14 неделях гестации. Критерии РАОП (2015) были использованы для оценки статуса витамина D. Антропометрическое исследование включало измерение роста, веса, окружности талии (ОТ) и расчет индекса массы тела (ИМТ). У 204 женщин в возрасте 30-52 лет проведена двухэнергетическая рентгеновская абсорбциометрия (ДРА) (Lunar Prodigy, USA). У 310 жителей 25-70 летнего возраста проведена оценка наличия тревоги и депрессии при помощи опросника госпитальной шкалы тревоги и депрессии HADS. За отсутствие тревоги и депрессии принималось суммарное значение баллов 0-7, за субклинические нарушения - 8-10, за клинические - >11. Результаты. Уровень 25(OH)D в сыворотке крови варьировал от 9,8 до 147,5 нмоль/л, у взрослых в среднем был 54,8±0,7нмоль/л, у детей/подростков - 46,8±1,6 нмоль/л. У женщин 25(OH)D крови был ниже чем у мужчин (53,9±0,8 и 67,2±2,2 нмоль/л; p
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- 2016
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117. UROVEN' OBESPEChENNOSTI VITAMINOM D I KOMPOZITsIONNYY SOSTAV TELA U SPORTSMENOV
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T L KARONOVA, P Yu GLOBA, A T ANDREEVA, S A ShIShKIN, M V BUDANOVA, and A A BAYRAMOV
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Osteopathy ,RZ301-397.5 - Abstract
Введение. Дефицит витамина D играет важную роль роли в патологии опорно-двигательной системы, однако данные о его влиянии на композиционный состав тела у профессиональных спортсменов весьма противоречивы. Цель исследования - определить уровень 25(ОН)D у молодых спортсменов и сопоставить с показателями количества жировой, соединительно-мышечной и костной ткани для уточнения распространенности дефицита витамина D и его вклада в формирование композиционного состава тела. Материал и методы. В исследование включено 186 спортсменов, 74 девушки и 112 юношей в возрасте от 16 до 20 лет (средний возраст 17,7±1,4 лет). Всем определено измерение роста, веса, рассчитан индекс массы тела (ИМТ, кг/м2). Уровень 25(ОН)D в сыворотке крови определен у 119 атлетов с помощью иммунохемилюминесцентного метода на анализаторе Architect 8000. Сорока семи спортсменам была выполнена двухэнергетическая рентгеновская абсорбциометрия (ДРА) в режиме total body с определением количества жировой, соединительно-мышечной и костной ткани. Результаты исследования продемонстрировали низкий уровень 25(ОН)D в сыворотке крови у 103 обследованных атлетов (86,6%), в том числе у 51,3% человек диагностирован дефицит витамина D. Гендерных различий в уровне в сыворотке крови выявлено не было. Уровень 25(ОН)D крови у атлетов, занимающихся в зале и более 2-х часов ежедневно на улице достоверно не отличался (21,9±1,2 и 21,1±0,9 нг/мл, p>0,05). Наименьший уровень 25(ОН)D был у баскетболистов, волейболистов, гандболистов, по сравнению с данным показателем у других атлетов (16,8±1,1 и 21,7±1,6 нг/мл, p0,05), ни с количеством соединительно-мышечной и костной ткани у обследованных спортсменов (r=-0,062, p>0,05). Выводы. Дефицит витамина D широко распространен среди спортсменов; тренировки на улице не влияют на уровень 25(ОН)D крови; атлеты командных видов спорта представляют группу риска по дефициту витамина D; дефицит витамина D не ассоциирован с меньшим количеством костной и мышечной массы у атлетов.
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- 2016
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118. Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.
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Taneva SG, Todinova S, and Andreeva T
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- Humans, Microscopy, Atomic Force, Blood Cells, Parkinson Disease diagnosis, Amyotrophic Lateral Sclerosis diagnosis, Alzheimer Disease diagnosis
- Abstract
Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today's society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs-Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD.
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- 2023
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119. Platelets' Nanomechanics and Morphology in Neurodegenerative Pathologies.
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Strijkova V, Todinova S, Andreeva T, Langari A, Bogdanova D, Zlatareva E, Kalaydzhiev N, Milanov I, and Taneva SG
- Abstract
The imaging and force-distance curve modes of atomic force microscopy (AFM) are explored to compare the morphological and mechanical signatures of platelets from patients diagnosed with classical neurodegenerative diseases (NDDs) and healthy individuals. Our data demonstrate the potential of AFM to distinguish between the three NDDs-Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and normal healthy platelets. The common features of platelets in the three pathologies are reduced membrane surface roughness, area and height, and enhanced nanomechanics in comparison with healthy cells. These changes might be related to general phenomena associated with reorganization in the platelet membrane morphology and cytoskeleton, a key factor for all platelets' functions. Importantly, the platelets' signatures are modified to a different extent in the three pathologies, most significant in ALS, less pronounced in PD and the least in AD platelets, which shows the specificity associated with each pathology. Moreover, different degree of activation, distinct pseudopodia and nanocluster formation characterize ALS, PD and AD platelets. The strongest alterations in the biophysical properties correlate with the highest activation of ALS platelets, which reflect the most significant changes in their nanoarchitecture. The specific platelet signatures that mark each of the studied pathologies can be added as novel biomarkers to the currently used diagnostic tools.
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- 2022
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120. Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.
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Jorstad SG, Marscher AP, Raiteri CM, Villata M, Weaver ZR, Zhang H, Dong L, Gómez JL, Perel MV, Savchenko SS, Larionov VM, Carosati D, Chen WP, Kurtanidze OM, Marchini A, Matsumoto K, Mortari F, Aceti P, Acosta-Pulido JA, Andreeva T, Apolonio G, Arena C, Arkharov A, Bachev R, Banfi M, Bonnoli G, Borman GA, Bozhilov V, Carnerero MI, Damljanovic G, Ehgamberdiev SA, Elsässer D, Frasca A, Gabellini D, Grishina TS, Gupta AC, Hagen-Thorn VA, Hallum MK, Hart M, Hasuda K, Hemrich F, Hsiao HY, Ibryamov S, Irsmambetova TR, Ivanov DV, Joner MD, Kimeridze GN, Klimanov SA, Knött J, Kopatskaya EN, Kurtanidze SO, Kurtenkov A, Kuutma T, Larionova EG, Leonini S, Lin HC, Lorey C, Mannheim K, Marino G, Minev M, Mirzaqulov DO, Morozova DA, Nikiforova AA, Nikolashvili MG, Ovcharov E, Papini R, Pursimo T, Rahimov I, Reinhart D, Sakamoto T, Salvaggio F, Semkov E, Shakhovskoy DN, Sigua LA, Steineke R, Stojanovic M, Strigachev A, Troitskaya YV, Troitskiy IS, Tsai A, Valcheva A, Vasilyev AA, Vince O, Waller L, Zaharieva E, and Chatterjee R
- Abstract
Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales
1-3 . This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5 , plasma instabilities6,7 or orbital motion in an accretion disc7,8 . Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref.9 ). BL Lac, the prototype of a subclass of blazars10 , is powered by a 1.7 × 108 MSun (ref.11 ) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref.12 )). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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121. Immune Tolerance Induction (ITI) with a pdFVIII/VWF Concentrate (octanate) in 100 Patients in the Observational ITI (ObsITI) Study.
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Escuriola Ettingshausen C, Vdovin V, Zozulya N, Svirin P, Andreeva T, Benedik-Dolničar M, Jiménez-Yuste V, Kitanovski L, Zupancic-Šalek S, Pavlova A, Bátorová A, Montaño Mejía C, Abdilova G, Knaub S, Jansen M, Lowndes S, Belyanskaya L, Walter O, and Oldenburg J
- Abstract
Background Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates., Competing Interests: Conflict of Interest C. Escuriola Ettingshausen has acted as a consultant and received speaker's fees and/or research funding from the following companies: Bayer, Biomarin, Biotest, Chugai, CSL Behring, Grifols, Kedrion, Novo Nordisk Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. V. Vdovin has participated in studies sponsored by Bayer, Generium, Novo Nordisk, Octapharma and Roche. N. Zozulya has acted as a consultant and received speaker's fees and/or research funding from the following companies: CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, SOBI and Takeda. T. Andreeva has received speaker's fees and/or research funding from Bayer, Baxalta, Biomarin, Catalis, CSL Behring, Generium, Grifols, Novo Nordisk, Octapharma and Roche, and has consulted for CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, Shire and Swedish Orphan Biovitrum. V Jiménez-Yuste has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Bayer, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. L. Kitanovski has acted as a consultant and received speaker's fees from the following companies: Bayer, Novo Nordisk, Octapharma, Roche, Takeda and Swedish Orphan Biovitrum. S. Zupančić Šalek has acted as a consultant and/or received speaker's fees and/or research funding from following companies: Bayer, Novo Nordisk, Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. A. Pavlova has participated in studies sponsored by Octapharma AG. A. Bátorová has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. C. Montaño Mejía has received speaker's fees from Octapharma and Roche; travel support from CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche and Takeda. J. Oldenburg has acted as a consultant and/or received speaker's fees, honoraria and research funding from the following companies: Bayer, Biogen Idec, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. S. Knaub, S. Lowndes, L. Belyanskaya and O. Walter are employees of Octapharma AG. M. Jansen is an employee of Octapharma Pharmazeutika Produktionsges.mbH. P. Svirin, M. Benedik-Dolničar and G. Abdilova stated that they had no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2022
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122. Global Seroprevalence of Pre-existing Immunity Against AAV5 and Other AAV Serotypes in People with Hemophilia A.
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Klamroth R, Hayes G, Andreeva T, Gregg K, Suzuki T, Mitha IH, Hardesty B, Shima M, Pollock T, Slev P, Oldenburg J, Ozelo MC, Stieltjes N, Castet SM, Mahlangu J, Peyvandi F, Kazmi R, Schved JF, Leavitt AD, Callaghan M, Pan-Petesch B, Quon DV, Andrews J, Trinh A, Li M, and Wong WY
- Subjects
- Antibodies, Neutralizing, Antibodies, Viral, Genetic Vectors genetics, Humans, Prospective Studies, Seroepidemiologic Studies, Serogroup, Dependovirus genetics, Hemophilia A epidemiology, Hemophilia A genetics, Hemophilia A therapy
- Abstract
Adeno-associated virus (AAV)-mediated gene therapy may provide durable protection from bleeding events and reduce treatment burden for people with hemophilia A (HA). However, pre-existing immunity against AAV may limit transduction efficiency and hence treatment success. Global data on the prevalence of AAV serotypes are limited. In this global, prospective, noninterventional study, we determined the prevalence of pre-existing immunity against AAV2, AAV5, AAV6, AAV8, and AAVrh10 among people ≥12 years of age with HA and residual FVIII levels ≤2 IU/dL. Antibodies against each serotype were detected using validated, electrochemiluminescent-based enzyme-linked immunosorbent assays. To evaluate changes in antibody titers over time, 20% of participants were retested at 3 and 6 months. In total, 546 participants with HA were enrolled at 19 sites in 9 countries. Mean (standard deviation) age at enrollment was 36.0 (14.87) years, including 12.5% younger than 18 years, and 20.0% 50 years of age and older. On day 1, global seroprevalence was 58.5% for AAV2, 34.8% for AAV5, 48.7% for AAV6, 45.6% for AAV8, and 46.0% for AAVrh10. Considerable geographic variability was observed in the prevalence of pre-existing antibodies against each serotype, but AAV5 consistently had the lowest seroprevalence across the countries studied. AAV5 seropositivity rates were 51.8% in South Africa ( n = 56), 46.2% in Russia ( n = 91), 40% in Italy ( n = 20), 37.2% in France ( n = 86), 26.8% in the United States ( n = 71), 26.9% in Brazil ( n = 26), 28.1% in Germany ( n = 89), 29.8% in Japan ( n = 84), and 5.9% in the United Kingdom ( n = 17). For all serotypes, seropositivity tended to increase with age. Serostatus and antibody titer were generally stable over the 6-month sampling period. As clinical trials of AAV-mediated gene therapies progress, data on the natural prevalence of antibodies against various AAV serotypes may become increasingly important.
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- 2022
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123. CVD-Synthesis of N-CNT Using Propane and Ammonia.
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Skudin V, Andreeva T, Myachina M, and Gavrilova N
- Abstract
N-CNT is a promising material for various applications, including catalysis, electronics, etc., whose widespread use is limited by the significant cost of production. CVD-synthesis using a propane-ammonia mixture is one of the cost-effective processes for obtaining carbon nanomaterials. In this work, the CVD-synthesis of N-CNT was conducted in a traditional bed reactor using catalyst: (Al
0,4 Fe0,48 Co0,12 )2 O3 + 3% MoO3 . The synthesized material was characterized by XPS spectroscopy, ASAP, TEM and SEM-microscopy. It is shown that the carbon material contains various morphological structures, including multiwalled carbon nanotubes (MWCNT), bamboo-like structures, spherical and irregular sections. The content of structures (bamboo-like and spherical structure) caused by the incorporation of nitrogen into the carbon nanotube structure depends on the synthesis temperature and the ammonia content in the reaction mixture. The optimal conditions for CVD-synthesis were determined: the temperature range (650-700 °C), the composition (C3 H8 /NH3 = 50/50%) and flow rate of the ammonia-propane mixture (200 mL/min).- Published
- 2022
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124. Morphometry and Stiffness of Red Blood Cells-Signatures of Neurodegenerative Diseases and Aging.
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Strijkova-Kenderova V, Todinova S, Andreeva T, Bogdanova D, Langari A, Danailova A, Krumova S, Zlatareva E, Kalaydzhiev N, Milanov I, and Taneva SG
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- Adult, Aged, Aged, 80 and over, Elastic Modulus physiology, Erythrocyte Count methods, Female, Humans, Male, Middle Aged, Aging pathology, Erythrocytes pathology, Neurodegenerative Diseases pathology
- Abstract
Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs)-Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies' RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young's modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified.
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- 2021
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125. Genetic Evidence of Authenticity of a Hair Shaft Relic from the Portrait of Tsesarevich Alexei, Son of the Last Russian Emperor.
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Andreeva T, Manakhov A, Kunizheva S, and Rogaev E
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- Humans, Russia, DNA, Mitochondrial genetics, Forensic Anthropology, Forensic Genetics, Hair, High-Throughput Nucleotide Sequencing
- Abstract
To determine the value of an art piece, authenticity of the artwork must be verified. We demonstrate here a genetic approach to determine origin of a historic relic in the museum piece. We tested two hair shafts of unknown origin framed into a watercolor portrait of Tsesarevich Alexei Romanov, son of the last Russian Tzar Nicholas II, which is a unique item kept in the State Historical Museum. Genetic identification of the hair shafts was performed by analysis of mitochondrial DNA (mtDNA) markers using both massive parallel genomic sequencing and multiplex targeted PCR, followed by Sanger sequencing. In previous works, we reconstructed the complete mtDNA sequence inherited to Alexei Romanov through the Queen Victoria lineage [Rogaev et al. (2009) Proc. Natl. Acad. Sci. USA, 106, 5258-5263]. DNA extracts were obtained from the two thin hair shafts and used for comparative genetic analysis. Despite the very low quantity and quality of the DNA templates retrieved from the historical single hair shaft specimen, informative mtDNA sequences were determined. The mtDNA haplotype in the hair shafts corresponds to the mtDNA haplotype of Tsarevich Alexei, his sisters, and his mother, Empress Alexandra Feodorovna. This haplotype remains unique in the currently available mtDNA databases. Our results reveal that the hair relic from the portrait is associated with the family of the last Russian Emperor Nicholas II. The study is an example of first application of the genetic methodology for verification of the value of museum artwork items.
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- 2021
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126. Publisher Correction: Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.
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Beidler CD, Smith HM, Alonso A, Andreeva T, Baldzuhn J, Beurskens MNA, Borchardt M, Bozhenkov SA, Brunner KJ, Damm H, Drevlak M, Ford OP, Fuchert G, Geiger J, Helander P, Hergenhahn U, Hirsch M, Höfel U, Kazakov YO, Kleiber R, Krychowiak M, Kwak S, Langenberg A, Laqua HP, Neuner U, Pablant NA, Pasch E, Pavone A, Pedersen TS, Rahbarnia K, Schilling J, Scott ER, Stange T, Svensson J, Thomsen H, Turkin Y, Warmer F, Wolf RC, and Zhang D
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- 2021
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127. Unprecedented formation of sterically stabilized phospholipid liposomes of cuboidal morphology.
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Bakardzhiev P, Forys A, Trzebicka B, Andreeva T, and Rangelov S
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- Doxorubicin, Lipid Bilayers, Polymers, Liposomes, Phospholipids
- Abstract
Sterically stabilized phospholipid liposomes of unprecedented cuboid morphology are formed upon introduction in the bilayer membrane of original polymers, based on polyglycidol bearing a lipid-mimetic residue. Strong hydrogen bonding in the polyglycidol sublayers creates attractive forces, which, facilitated by fluidization of the membrane, bring about the flattening of the bilayers and the formation of cuboid vesicles.
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- 2021
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128. Functionalization of Aminoalkylsilane-Grafted Bacterial Nanocellulose with ZnO-NPs-Doped Pullulan Electrospun Nanofibers for Multifunctional Wound Dressing.
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Shahriari-Khalaji M, Hu G, Chen L, Cao Z, Andreeva T, Xiong X, Krastev R, and Hong FF
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- Animals, Bandages, Glucans, Rats, Nanofibers, Nanoparticles, Zinc Oxide
- Abstract
High moisture permeability, excellent mechanical properties in a wet state, high water-holding capability, and high exudate absorption make bacterial nanocellulose (BNC) a favorable candidate for biomedical device production, especially wound dressings. The lack of antibacterial activity and healing-promoting ability are the main drawbacks that limit its wide application. Pullulan (Pul) is a nontoxic polymer that can promote wound healing. Zinc oxide nanoparticles (ZnO-NPs) are well-known as a safe antibacterial agent. In this study, aminoalkylsilane was chemically grafted on a BNC membrane (A- g -BNC) and used as a bridge to combine BNC with Pul-ZnO-NPs hybrid electrospun nanofibers. FTIR results confirmed the successful production of A- g -BNC/Pul-ZnO. The obtained dressing demonstrated blood clotting performance better than that of BNC. The dressing showed an ability to release ZnO, and its antibacterial activity was up to 5 log values higher than that of BNC. The cytotoxicity of the dressing toward L929 fibroblast cells clearly showed safety due to the proliferation of fibroblast cells. The animal test in a rat model indicated faster healing and re-epithelialization, small blood vessel formation, and collagen synthesis in the wounds covered by A- g -BNC/Pul-ZnO. The new functional dressing, fabricated with a cost-effective and easy method, not only showed excellent antibacterial activity but could also accelerate wound healing.
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- 2021
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129. Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.
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Beidler CD, Smith HM, Alonso A, Andreeva T, Baldzuhn J, Beurskens MNA, Borchardt M, Bozhenkov SA, Brunner KJ, Damm H, Drevlak M, Ford OP, Fuchert G, Geiger J, Helander P, Hergenhahn U, Hirsch M, Höfel U, Kazakov YO, Kleiber R, Krychowiak M, Kwak S, Langenberg A, Laqua HP, Neuner U, Pablant NA, Pasch E, Pavone A, Pedersen TS, Rahbarnia K, Schilling J, Scott ER, Stange T, Svensson J, Thomsen H, Turkin Y, Warmer F, Wolf RC, and Zhang D
- Abstract
Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak
1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2 , a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4 . The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5 . Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization., (© 2021. The Author(s).)- Published
- 2021
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130. Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia.
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Andreeva T, Komsa-Penkova R, Langari A, Krumova S, Golemanov G, Georgieva GB, Taneva SG, Giosheva I, Mihaylova N, Tchorbanov A, and Todinova S
- Subjects
- Abortion, Habitual etiology, Abortion, Habitual metabolism, Adult, Blood Platelets metabolism, Case-Control Studies, Female, Humans, Pregnancy, Abortion, Habitual pathology, Blood Platelets pathology, Nanostructures chemistry, Polymorphism, Genetic, Thrombophilia complications
- Abstract
Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients' platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) ( p < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) ( p < 0.05), strong alteration in the membrane Young modulus, increased production of platelets' microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia ( FVL , FII20210A , PLA1/A2 , MTHFR C677T or 4G/5G PAI-1 ) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes.
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- 2021
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131. Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course.
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Yukina M, Erofeeva T, Nuralieva N, Andreeva T, Savvateeva E, Dudko N, Troshina E, Rogaev E, and Melnichenko G
- Abstract
Context: Autoimmune polyglandular syndrome (APS) is a cluster of endocrine disorders arising from immune dysregulation, often combined with damage to nonendocrine organs. There are 2 types of APS: type 1 and type 2 (APS-1 and APS-2, respectively). In clinical practice, an atypical course of APS is often observed., Objective: This work aims to find a novel genetic predictor of APS., Methods: We performed exome sequencing in 2 patients with an atypical clinical APS picture and members of their families. Patient A presented with a manifestation of APS-2 in early childhood and patient B with a late manifestation of the main components of APS-1., Results: In patient B, we identified inherited compound mutations as a novel combination of the c.769C > T and c.821delG alleles of AIRE and genetic variation in the CIITA gene. No homozygous or compound mutations in AIRE were found in patient A, but we did reveal mutations in genes encoding regulatory proteins of innate and acquired immunity in this patient., Conclusion: Our data revealed novel combination of mutations in the AIRE gene in atypical APS and imply that mutations in immune-related genes may modify the clinical manifestation of APS in AIRE -mutation carriers and contribute to the development of autoimmune pathology in non-AIRE carriers with atypical APS., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2021
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132. Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABA A and Nicotinic Acetylcholine Receptors.
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Son L, Kryukova E, Ziganshin R, Andreeva T, Kudryavtsev D, Kasheverov I, Tsetlin V, and Utkin Y
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- Animals, Binding Sites, Binding, Competitive, Cell Line, Tumor, Cholinergic Agents metabolism, Cobra Neurotoxin Proteins metabolism, GABA-A Receptor Antagonists metabolism, Membrane Potentials, Mice, Protein Binding, Protein Conformation, Receptors, GABA genetics, Receptors, GABA metabolism, Structure-Activity Relationship, Torpedo, Xenopus laevis, alpha7 Nicotinic Acetylcholine Receptor metabolism, Cholinergic Agents pharmacology, Cobra Neurotoxin Proteins pharmacology, Elapid Venoms metabolism, GABA-A Receptor Antagonists pharmacology, Naja, Receptors, GABA drug effects, alpha7 Nicotinic Acetylcholine Receptor drug effects
- Abstract
Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABA
A receptors (GABAA Rs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAA R and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedo californica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAA Rs, showed that all toxins interacted with the GABAA R much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAA R was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAA R. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.- Published
- 2021
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133. Condensing Effect of Cholesterol on hBest1/POPC and hBest1/SM Langmuir Monolayers.
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Videv P, Mladenov N, Andreeva T, Mladenova K, Moskova-Doumanova V, Nikolaev G, Petrova SD, and Doumanov JA
- Abstract
Human bestrophin-1 protein (hBest1) is a transmembrane channel associated with the calcium-dependent transport of chloride ions in the retinal pigment epithelium as well as with the transport of glutamate and GABA in nerve cells. Interactions between hBest1, sphingomyelins, phosphatidylcholines and cholesterol are crucial for hBest1 association with cell membrane domains and its biological functions. As cholesterol plays a key role in the formation of lipid rafts, motional ordering of lipids and modeling/remodeling of the lateral membrane structure, we examined the effect of different cholesterol concentrations on the surface tension of hBest1/POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and hBest1/SM Langmuir monolayers in the presence/absence of Ca
2+ ions using surface pressure measurements and Brewster angle microscopy studies. Here, we report that cholesterol: (1) has negligible condensing effect on pure hBest1 monolayers detected mainly in the presence of Ca2+ ions, and; (2) induces a condensing effect on composite hBest1/POPC and hBest1/SM monolayers. These results offer evidence for the significance of intermolecular protein-lipid interactions for the conformational dynamics of hBest1 and its biological functions as multimeric ion channel.- Published
- 2021
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134. Opinion: Cultural and linguistic diversities are underappreciated pillars of biodiversity.
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Frainer A, Mustonen T, Hugu S, Andreeva T, Arttijeff EM, Arttijeff IS, Brizoela F, Coelho-de-Souza G, Printes RB, Prokhorova E, Sambou S, Scherer A, Shadrin V, and Pecl G
- Subjects
- Brazil, Europe, Humans, Linguistics, Senegal, Taiwan, Biodiversity, Cultural Diversity, Language
- Abstract
Competing Interests: The authors declare no competing interest.
- Published
- 2020
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135. Providers' Initial Trust on an Organization-Sponsored Sharing Platform: The Framing of Coworker Collaborative Consumption.
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Bhappu AD, Blomqvist K, Andreeva T, Zappa P, Yeo ML, and Lempiälä T
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Organization-sponsored sharing platforms extend the sharing economy to workplaces by connecting employees in a private online community where they can socially exchange goods and services with coworkers. Employees share costs but do not earn income during this collaborative consumption. Furthermore, employers pay for their employees to have access to the platform technology and any related transaction fees. Trust is a crucial antecedent for engagement on sharing platforms because it helps mitigate risks during collaborative consumption. However, the literature on trust in the sharing economy has focused almost exclusively on platforms that broker peer-to-peer rental transactions rather than social exchanges. There is also a lack of research about providers' perspectives. We address these gaps by investigating the nature of trust among employees who initially provide goods and services on an organization-sponsored sharing platform. We also explore how these employees' initial trust influences their collaborative consumption with coworkers. Through abductive analysis of 22 interviews with 15 providers on an organization-sponsored sharing platform, we shed light on how employees initially develop trust when providing goods and services to coworkers. By integrating prior research on initial trust among employees and cognitive framing with in-depth qualitative insights, we develop a conceptual model depicting how identity, interaction and issue frames shape these providers' beliefs about coworker trustworthiness and intended sharing strategy. In particular, our empirical findings reveal that employees' social categorization, illusions of control and engagement motive framed their initial trust and enactment of collaborative consumption as citizens in a community or consumers in a marketplace., (Copyright © 2020 Bhappu, Blomqvist, Andreeva, Zappa, Yeo and Lempiälä.)
- Published
- 2020
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136. Genetic Association Between Alzheimer's Disease Risk Variant of the PICALM Gene and EEG Functional Connectivity in Non-demented Adults.
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Ponomareva N, Andreeva T, Protasova M, Konovalov R, Krotenkova M, Malina D, Mitrofanov A, Fokin V, Illarioshkin S, and Rogaev E
- Abstract
Genome wide association studies (GWAS) have identified and validated the association of the PICALM genotype with Alzheimer's disease (AD). The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain functional connectivity in non-demented subjects remains largely unknown. We examined the association of the PICALM rs3851179 genotype with the characteristics of lagged linear connectivity (LLC) of resting EEG sources in 104 non-demented adults younger than 60 years of age. The EEG analysis was performed using exact low-resolution brain electromagnetic tomography (eLORETA) freeware (Pascual-Marqui et al., 2011). We found that the carriers of the A PICALM allele ( PICALM AA and AG genotypes) had higher widespread interhemispheric LLC of alpha sources compared to the carriers of the GG PICALM allele. An exploratory correlation analysis showed a moderate positive association between the alpha LLC interhemispheric characteristics and the corpus callosum size and between the alpha interhemispheric LLC characteristics and the Luria word memory scores. These results suggest that the PICALM rs3851179 A allele provides protection against cognitive decline by facilitating neurophysiological reserve capacities in non-demented adults. In contrast, lower functional connectivity in carriers of the AD risk variant, PICALM GG , suggests early functional alterations in alpha rhythm networks., (Copyright © 2020 Ponomareva, Andreeva, Protasova, Konovalov, Krotenkova, Malina, Mitrofanov, Fokin, Illarioshkin and Rogaev.)
- Published
- 2020
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137. Dissection of the Human T-Cell Receptor γ Gene Repertoire in the Brain and Peripheral Blood Identifies Age- and Alzheimer's Disease-Associated Clonotype Profiles.
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Aliseychik M, Patrikeev A, Gusev F, Grigorenko A, Andreeva T, Biragyn A, and Rogaev E
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- Adult, Aged, Aged, 80 and over, Complementarity Determining Regions genetics, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Pilot Projects, Receptors, Antigen, T-Cell, gamma-delta blood, Receptors, Antigen, T-Cell, gamma-delta immunology, Young Adult, Aging blood, Aging immunology, Alzheimer Disease blood, Alzheimer Disease immunology, Brain immunology, Clone Cells immunology, Genes, T-Cell Receptor gamma, Receptors, Antigen, T-Cell, gamma-delta genetics
- Abstract
The immune system contributes to neurodegenerative pathologies. However, the roles of γδ T cells in Alzheimer's disease (AD) are poorly understood. Here, we evaluated somatic variability of T-cell receptor γ genes (TRGs) in patients with AD. We performed deep sequencing of the CDR3 region of TRGs in patients with AD and control patients without dementia. TRG clones were clearly detectable in peripheral blood (PB) and non-neuronal cell populations in human brains. TRG repertoire diversity was reduced during aging. Compared with the PB, the brain showed reduced TRGV9 clonotypes but was enriched in TRGV2/4/8 clonotypes. AD-associated TRG profiles were found in both the PB and brain. Moreover, some groups of clonotypes were more specific for the brain or blood in patients with AD compared to those in controls. Our pilot deep analysis of T-cell receptor diversities in AD revealed putative brain and AD-associated immunogenic markers., (Copyright © 2020 Aliseychik, Patrikeev, Gusev, Grigorenko, Andreeva, Biragyn and Rogaev.)
- Published
- 2020
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138. Desiccation-induced alterations in surface topography of thylakoids from resurrection plant Haberlea rhodopensis studied by atomic force microscopy, electrokinetic and optical measurements.
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Doltchinkova V, Andreeva T, Georgieva K, Mihailova G, and Balashev K
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- Craterostigma radiation effects, Droughts, Craterostigma metabolism, Desiccation, Light, Microscopy, Atomic Force methods, Thylakoids metabolism
- Abstract
With their ability to survive complete desiccation, resurrection plants are a suitable model system for studying the mechanisms of drought tolerance. In the present study, we investigated desiccation-induced alterations in surface topography of thylakoids isolated from well-hydrated, moderately dehydrated, severely desiccated and rehydrated Haberlea rhodopensis plants by means of atomic force microscopy (AFM), electrokinetic and optical measurements. According to our knowledge, so far, there were no reports on the characterization of surface topography and polydispersity of thylakoid membranes from resurrection plants using AFM and dynamic light scattering. To study the physicochemical properties of thylakoids from well-hydrated H. rhodopensis plants, we used spinach thylakoids for comparison as a classical model from higher plants. The thylakoids from well-hydrated H. rhodopensis had a grainy surface, significantly different from the well-structured spinach thylakoids with distinct grana and lamella, they had twice smaller cross-sectional area and were 1.5 times less voluminous than that of spinach. Significant differences in their physicochemical properties were observed. The dehydration and subsequent rehydration of plants affected the size, shape, morphology, roughness and therefore the structure of the studied thylakoids. Drought resulted in significant enhancement of negative charges on the outer surface of thylakoid membranes which correlated with the increased roughness of thylakoid surface. This enhancement in surface charge density could be due to the partial unstacking of thylakoids exposing more negatively charged groups from protein complexes on the membrane surface that prevent from possible aggregation upon drought stress., (© 2018 Scandinavian Plant Physiology Society.)
- Published
- 2019
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139. Aminated Graphene Oxide as a Potential New Therapy for Colorectal Cancer.
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Krasteva N, Keremidarska-Markova M, Hristova-Panusheva K, Andreeva T, Speranza G, Wang D, Draganova-Filipova M, Miloshev G, and Georgieva M
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- Animals, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Shape, Cell Survival, Colorectal Neoplasms pathology, DNA Damage, Mice, Nanoparticles chemistry, Nanoparticles ultrastructure, Reactive Oxygen Species metabolism, Amines therapeutic use, Colorectal Neoplasms therapy, Graphite therapeutic use
- Abstract
Nanotechnology-based drug delivery systems for cancer therapy are the topic of interest for many researchers and scientists. Graphene oxide (GO) and its derivates are among the most extensively studied delivery systems of this type. The increased surface area, elevated loading capacity, and aptitude for surface functionalization together with the ability to induce reactive oxygen species make GO a promising tool for the development of novel anticancer therapies. Moreover, GO nanoparticles not only function as effective drug carriers but also have the potential to exert their own inhibitory effects on tumour cells. Recent results show that the functionalization of GO with different functional groups, namely, with amine groups, leads to increased reactivity of the nanoparticles. The last steers different hypotheses for the mechanisms through which this functionalization of GO could potentially lead to improved anticancer capacity. In this research, we have evaluated the potential of amine-functionalized graphene oxide nanoparticles (GO-NH
2 ) as new molecules for colorectal cancer therapy. For the purpose, we have assessed the impact of aminated graphene oxide (GO) sheets on the viability of colon cancer cells, their potential to generate ROS, and their potential to influence cellular proliferation and survival. In order to elucidate their mechanism of action on the cellular systems, we have probed their genotoxic and cytostatic properties and compared them to pristine GO. Our results revealed that both GO samples (pristine and aminated) were composed of few-layer sheets with different particle sizes, zeta potential, and surface characteristics. Furthermore, we have detected increased cyto- and genotoxicity of the aminated GO nanoparticles following 24-hour exposure on Colon 26 cells. The last leads us to conclude that exposure of cancer cells to GO, namely, aminated GO, can significantly contribute to cancer cell killing by enhancing the cytotoxicity effect exerted through the induction of ROS, subsequent DNA damage, and apoptosis.- Published
- 2019
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140. Impact of age and comorbidities on the efficacy of FC and FCR regimens in chronic lymphocytic leukemia.
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Strugov V, Stadnik E, Virts Y, Andreeva T, and Zaritskey A
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- Adult, Aged, Comorbidity, Female, Humans, Male, Middle Aged, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality
- Abstract
CLL is an aging-associated neoplasm with median age at diagnosis > 65 years. Little is known about safety and efficacy of FC/FCR regimens in elderly CLL patients with multiple comorbidities. We retrospectively revised medical records of 90 patients treated with FC/FCR regimens in our clinic. Data on demographic and biological characteristics, comorbidities, response to therapy, and treatment-associated adverse events were analyzed. Compared to FC, FCR yielded higher rates of OR (93.6 vs. 81.4%, p = .109) and CR (72.3 vs. 46.5%, p = .018). This translated in longer EFS (median 52 vs. 19 months, p = <.001) and OS (median 89 vs. 45 months, p = .001). Elderly patients (≥ 65 years) had more comorbidities and higher median CIRS-G score (7 vs. 4, p < .001). However, no association was found between CIRS-G score and survival. Decreased renal function was associated with dismal prognosis in patients treated with FCR.
- Published
- 2018
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141. Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults.
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Pilsner JR, Shershebnev A, Medvedeva YA, Suvorov A, Wu H, Goltsov A, Loukianov E, Andreeva T, Gusev F, Manakhov A, Smigulina L, Logacheva M, Shtratnikova V, Kuznetsova I, Speranskiy-Podobed P, Burns JS, Williams PL, Korrick S, Lee MM, Rogaev E, Hauser R, and Sergeyev O
- Subjects
- Adolescent, Adult, Child, Environmental Monitoring, Humans, Male, Puberty, Russia, Whole Genome Sequencing, Young Adult, DNA Methylation, Endocrine Disruptors blood, Environmental Pollutants blood, Polychlorinated Dibenzodioxins blood, Spermatozoa metabolism
- Abstract
Background: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown., Objective: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood., Methods: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age. WGBS of sperm was conducted to identify differentially methylated regions (DMR) between highest (n = 4) and lowest (n = 4) peripubertal TCDD groups., Results: We found 52 DMRs that distinguished lowest and highest peripubertal serum TCDD concentrations. One of the top scoring networks, "Cellular Assembly and Organization, Cellular Function and Maintenance, Carbohydrate Metabolism", identified estrogen receptor alpha as its central regulator., Conclusion: Findings from our limited sample size suggest that peripubertal environmental exposures are associated with sperm DNA methylation in young adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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142. Sexual Function, Mental Well-being and Quality of Life among Kurdish Circumcised Women in Iran.
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Daneshkhah F, Allahverdipour H, Jahangiri L, and Andreeva T
- Abstract
Background: Female genital mutilation is an intentional inhumane procedure that threatens girls and women's health. It is especially widespread in developing countries due to cultural, traditional and religious preferences. The aim of the current study was to investigate how circumcision affects women's sexual function., Methods: This cross-sectional study was conducted in the urban and rural area of Piranshahr County, Iran, in 2015 among convenience samples of 200 women, 15-49 yr old, who were applying to health care centers for receiving routine health care services. Data collection was conducted with the use of a self-administered written questionnaire to assess female sexual function, mental well-being, and quality of life., Results: Significant differences were found between circumcised and non-circumcised women in total score of female sexual function index (FSFI) in domains of desire, arousal, vaginal moisture, orgasm, satisfaction, and pain [( P <0.001), MD(95%CI)=5.64(3.64 to 7.64)] and based on Hotelling's T-square, significant differences were found in dimensions of quality of life and FSFI., Conclusion: The revealed sexual dysfunction among mutilated women gives ground to require that public health systems take actions aimed at implementing special sexual education program to improve sexual functions of mutilated women and changing beliefs and social norms in the community level., Competing Interests: Conflict of Interests The authors declare that there is no conflict of interest.
- Published
- 2017
143. Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A.
- Author
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Giangrande P, Andreeva T, Chowdary P, Ehrenforth S, Hanabusa H, Leebeek FW, Lentz SR, Nemes L, Poulsen LH, Santagostino E, You CW, Clausen WH, Jönsson PG, and Oldenburg J
- Subjects
- Adolescent, Adult, Aged, Child, Coagulants adverse effects, Coagulants pharmacokinetics, Drug Administration Schedule, Factor VIII adverse effects, Factor VIII pharmacokinetics, Hemophilia A blood, Hemophilia A diagnosis, Hemorrhage blood, Humans, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Young Adult, Coagulants administration & dosage, Factor VIII administration & dosage, Hemophilia A drug therapy, Hemorrhage prevention & control, Hemostasis drug effects
- Abstract
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.
- Published
- 2017
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144. Overview of diagnostic performance and results for the first operation phase in Wendelstein 7-X (invited).
- Author
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Krychowiak M, Adnan A, Alonso A, Andreeva T, Baldzuhn J, Barbui T, Beurskens M, Biel W, Biedermann C, Blackwell BD, Bosch HS, Bozhenkov S, Brakel R, Bräuer T, Brotas de Carvalho B, Burhenn R, Buttenschön B, Cappa A, Cseh G, Czarnecka A, Dinklage A, Drews P, Dzikowicka A, Effenberg F, Endler M, Erckmann V, Estrada T, Ford O, Fornal T, Frerichs H, Fuchert G, Geiger J, Grulke O, Harris JH, Hartfuß HJ, Hartmann D, Hathiramani D, Hirsch M, Höfel U, Jabłoński S, Jakubowski MW, Kaczmarczyk J, Klinger T, Klose S, Knauer J, Kocsis G, König R, Kornejew P, Krämer-Flecken A, Krawczyk N, Kremeyer T, Książek I, Kubkowska M, Langenberg A, Laqua HP, Laux M, Lazerson S, Liang Y, Liu SC, Lorenz A, Marchuk AO, Marsen S, Moncada V, Naujoks D, Neilson H, Neubauer O, Neuner U, Niemann H, Oosterbeek JW, Otte M, Pablant N, Pasch E, Sunn Pedersen T, Pisano F, Rahbarnia K, Ryć L, Schmitz O, Schmuck S, Schneider W, Schröder T, Schuhmacher H, Schweer B, Standley B, Stange T, Stephey L, Svensson J, Szabolics T, Szepesi T, Thomsen H, Travere JM, Trimino Mora H, Tsuchiya H, Weir GM, Wenzel U, Werner A, Wiegel B, Windisch T, Wolf R, Wurden GA, Zhang D, Zimbal A, and Zoletnik S
- Abstract
Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.
- Published
- 2016
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145. Clusters of alpha satellite on human chromosome 21 are dispersed far onto the short arm and lack ancient layers.
- Author
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Ziccardi W, Zhao C, Shepelev V, Uralsky L, Alexandrov I, Andreeva T, Rogaev E, Bun C, Miller E, Putonti C, and Doering J
- Subjects
- Base Sequence, Chromosomes, Artificial, Bacterial genetics, Humans, In Situ Hybridization, Fluorescence, Phylogeny, Repetitive Sequences, Nucleic Acid, Centromere genetics, Chromosome Mapping, Chromosomes, Human, Pair 21 genetics, DNA, Satellite genetics, Evolution, Molecular, Multigene Family genetics
- Abstract
Human alpha satellite (AS) sequence domains that currently function as centromeres are typically flanked by layers of evolutionarily older AS that presumably represent the remnants of earlier primate centromeres. Studies on several human chromosomes reveal that these older AS arrays are arranged in an age gradient, with the oldest arrays farthest from the functional centromere and arrays progressively closer to the centromere being progressively younger. The organization of AS on human chromosome 21 (HC21) has not been well-characterized. We have used newly available HC21 sequence data and an HC21p YAC map to determine the size, organization, and location of the AS arrays, and compared them to AS arrays found on other chromosomes. We find that the majority of the HC21 AS sequences are present on the p-arm of the chromosome and are organized into at least five distinct isolated clusters which are distributed over a larger distance from the functional centromere than that typically seen for AS on other chromosomes. Using both phylogenetic and L1 element age estimations, we found that all of the HC21 AS clusters outside the functional centromere are of a similar relatively recent evolutionary origin. HC21 contains none of the ancient AS layers associated with early primate evolution which is present on other chromosomes, possibly due to the fact that the p-arm of HC21 and the other acrocentric chromosomes underwent substantial reorganization about 20 million years ago.
- Published
- 2016
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146. Fast bistable intensive light scattering in helix-free ferroelectric liquid crystals.
- Author
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Andreev A, Andreeva T, Kompanets I, Zalyapin N, Xu H, Pivnenko M, and Chu D
- Abstract
A new type of ferroelectric liquid crystal (FLC) is considered, where the reorientation of the director (main optical axes) at the interaction of an electric field with the FLC's spontaneous polarization is due to the movement of spatially localized waves with a stationary profile: solitons arise at the transition due to the Maxwellian mechanism of energy dissipation. Under certain conditions, the appearance of such waves leads to the formation of a structure of transient domains, and as a consequence, to the scattering of light. The Maxwellian mechanism of energy dissipation allows one to reduce the electric field strength at which the maximum efficiency of light scattering is achieved down to 2-3 V/μm and to increase the frequency of light modulation up to 3-5 kHz. Intensive bistable light scattering in an electro-optical cell filled with a specially designed helix-free FLC was studied, and a stable scattering state can be switched on and off for a few tens of microseconds and memorized for a few tens of seconds.
- Published
- 2016
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147. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.
- Author
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Kreuz W, Escuriola Ettingshausen C, Vdovin V, Zozulya N, Plyushch O, Svirin P, Andreeva T, Bubanská E, Campos M, Benedik-Dolničar M, Jiménez-Yuste V, Kitanovski L, Klukowska A, Momot A, Osmulskaya N, Prieto M, Šalek SZ, Velasco F, Pavlova A, Oldenburg J, Knaub S, Jansen M, Belyanskaya L, and Walter O
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Drug Combinations, Factor VIII adverse effects, Female, Hemophilia A complications, Hemorrhage complications, Humans, Infant, Male, Prognosis, Prospective Studies, Risk Factors, Safety, Young Adult, von Willebrand Factor adverse effects, Antibodies, Neutralizing immunology, Factor VIII immunology, Factor VIII therapeutic use, Hemophilia A drug therapy, Hemophilia A immunology, Immune Tolerance drug effects, von Willebrand Factor immunology, von Willebrand Factor therapeutic use
- Abstract
Introduction/background: Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment., Aim: The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors., Patients/methods: Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (<5 BU) received 50-100 IU FVIII kg(-1) daily, or every other day; 'high responders' (≥5 BU) received 100 IU FVIII kg(-1) every 12 h., Results: Forty of 48 patients (83.3%), had at least one risk factor for poor ITI-prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success., Conclusion: Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success., (© 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)
- Published
- 2016
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148. Real-life evidence in evaluating effectiveness of treatment in Haemophilia A with a recombinant FVIII concentrate: a non-interventional study in emerging countries.
- Author
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Gouider E, Rauchensteiner S, Andreeva T, Al Zoebie A, Mehadzic S, Nefyodova L, Brunn M, Tueckmantel C, and Meddeb B
- Subjects
- Adolescent, Adult, Aged, Blood Coagulation Factor Inhibitors, Child, Child, Preschool, Factor VIII administration & dosage, Factor VIII adverse effects, Hemophilia A complications, Humans, Infant, Infections etiology, Isoantibodies, Joint Diseases etiology, Male, Middle Aged, Premedication, Sucrose administration & dosage, Sucrose adverse effects, Treatment Outcome, Young Adult, Factor VIII therapeutic use, Hemophilia A drug therapy, Sucrose therapeutic use
- Abstract
Some progress has been made regarding availability of recombinant factor VIII concentrates and prophylaxis for haemophilia A in emerging countries, where plasma-derived concentrates were used in the vast majority. Clinical studies to document their introduction and effectiveness are so far not widely available in literature. This non-interventional study evaluates the real-life effectiveness and safety of prophylactic and on-demand treatment with recombinant factor VIII formulated with sucrose (rFVIII-FS) for bleed control and preservation of joints in emerging countries from Eastern Europe, North Africa and Middle East area. One hundred and eighty-six patients from 11 countries were enrolled, mean ± SD age 12.8 ± 12.7 years. At enrolment, majority (79.6%) had severe haemophilia A (<2% IU mL(-1) ), 47.8% had a target joint, 15% had an inhibitor history and one patient was on immune tolerance induction. During the 24-month observation period, 58.1% of the patients were prescribed prophylaxis at every visit, 31.7% were on an on-demand regimen. Patients with severe haemophilia A on prophylaxis (n = 82) had a mean annual rate of treated bleeds of 2.8 ± 4.4, whereas it was 19.1 ± 32.0 for the on-demand group (n = 31), and a mean total Gilbert Score of 9.9 ± 10.3 at baseline and 4.1 ± 6.7 at study end; vs. 15.2 ± 17.3 and 13.7 ± 17.1 for on-demand respectively. The majority of the bleeds (91.1%) were treated with one or two infusions. Four patients without inhibitor history had a first positive inhibitor test during the study. This study demonstrates the effective use of rFVIII-FS in emerging countries and adds to the established safety profile of rFVIII-FS., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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149. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial.
- Author
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Urasinski T, Stasyshyn O, Andreeva T, Rusen L, Perina FG, Oh MS, Chapman M, Pavlova BG, Valenta-Singer B, and Abbuehl BE
- Subjects
- Adolescent, Age Factors, Child, Child, Preschool, Female, Hemophilia B blood, Hemophilia B complications, Hemorrhage drug therapy, Hemorrhage etiology, Hemorrhage prevention & control, Humans, Infant, Male, Premedication, Retreatment, Time Factors, Treatment Outcome, Factor IX pharmacology, Factor IX therapeutic use, Hemophilia B drug therapy, Recombinant Proteins pharmacology, Recombinant Proteins therapeutic use
- Abstract
A newly developed recombinant factor IX (BAX326(1) ) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1-2%) haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment-related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty-six bleeds (19 non-joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury-related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1-2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B., (© 2014 John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
150. Low pH modulates the macroorganization and thermal stability of PSII supercomplexes in grana membranes.
- Author
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Stoichev S, Krumova SB, Andreeva T, Busto JV, Todinova S, Balashev K, Busheva M, Goñi FM, and Taneva SG
- Subjects
- Enzyme Stability, Hot Temperature, Hydrogen-Ion Concentration, Pisum sativum chemistry, Pisum sativum enzymology, Pisum sativum ultrastructure, Protein Denaturation, Thylakoids enzymology, Photosystem II Protein Complex chemistry, Thylakoids chemistry
- Abstract
Protonation of the lumen-exposed residues of some photosynthetic complexes in the grana membranes occurs under conditions of high light intensity and triggers a major photoprotection mechanism known as energy dependent nonphotochemical quenching. We have studied the role of protonation in the structural reorganization and thermal stability of isolated grana membranes. The macroorganization of granal membrane fragments in protonated and partly deprotonated state has been mapped by means of atomic force microscopy. The protonation of the photosynthetic complexes has been found to induce large-scale structural remodeling of grana membranes-formation of extensive domains of the major light-harvesting complex of photosystem II and clustering of trimmed photosystem II supercomplexes, thinning of the membrane, and reduction of its size. These events are accompanied by pronounced thermal destabilization of the photosynthetic complexes, as evidenced by circular dichroism spectroscopy and differential scanning calorimetry. Our data reveal a detailed nanoscopic picture of the initial steps of nonphotochemical quenching., (Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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