Accurate free and forced rotational motions of rigid Venus

% context :The precise and accurate modelling of a terrestrial planet like Venus is an exciting and challenging topic, all the more interesting since it can be compared with that of the Earth for which such a modelling has already been achieved at the milliarcsecond level % aims: We want to complete a previous study (Cottereau and Souchay, 2009), by determining at the milliarcsecond level the polhody, i.e. the torque-free motion of the axis of angular momentum of a rigid Venus in a body-fixed frame, as well as the nutation of its third axis of figure in space, which is fundamental from an observational point of view. results :In a first part we have computed the polhody, i.e. the respective free rotational motion of the axis of angular momentum of Venus with respect to a body-fixed frame. We have shown that this motion is highly elliptical, with a very long period of 525 cy to be compared with 430 d for the Earth. This is due to the very small dynamical flattening of Venus in comparison with our planet. In a second part we have computed precisely the Oppolzer terms which allow to represent the motion in space of the third Venus figure axis with respect to Venus angular momentum axis, under the influence of the solar gravitational torque. We have determined the corresponding tables of coefficients of nutation of the third figure axis both in longitude and in obliquity due to the Sun, which are of the same order of amplitude as for the Earth. We have shown that the coefficients of nutation for the third figure axis are significantly different from those of the angular momentum axis on the contrary of the Earth. Our analytical results have been validated by a numerical integration which revealed the indirect planetary effects.Comment: 14 pages, 11 figures, accepted for publication in section 11. Celestial mechanics and astrometry of Astronomy and Astrophysics (27/02/2010

Comparison of Postural Recovery Following Short and Long Duration Spaceflights

INTRODUCTION: Post-flight postural ataxia reflects adaptive changes to vestibulo-spinal reflexes and control strategies adopted for movement in weightlessness. Quantitative measures obtained during computerized dynamic posturography (CDP) from US and Russian programs provide insight into the effect of spaceflight duration in terms of both the initial decrements and recovery of postural stability. METHODS: CDP was obtained on 117 crewmembers following Shuttle flights lasting 4-17 days, and on 64 crewmembers following long-duration missions lasting 48-380 days. Although the number and timing of sessions varied, the goal was to characterize postural recovery pooling similar measures from different research and flight medicine programs. This report focuses on eyes closed, head erect conditions with either a fixed or sway-referenced base of support. A smaller subset of subjects repeated the sway-referenced condition while making pitch head movements (+/- 20deg at 0.33Hz). Equilibrium scores were derived from peak-to-peak anterior-posterior sway. Fall probability was modeled using Bayesian statistical methods to estimate parameters of a logit function. RESULTS: The standard Romberg condition was the least sensitive. Longer duration flights led to larger decrements in stability with sway-reference support during the first 1-2 days, although the timecourse of recovery was similar across flight duration with head erect. Head movements led to increased incidence of falls during the first week, with a significantly longer recovery following long duration flights. CONCLUSIONS: The diagnostic assessment of postural instability, and differences in the timecourse of postural recovery between short and long flight durations, are more pronounced during unstable support conditions requiring active head movements

Development of Training Programs to Optimize Planetary Ambulation

Astronauts experience disturbances in functional mobility following their return to Earth due to adaptive responses that occur during exposure to the microgravity conditions of space flight. Despite significant time spent performing in-flight exercise routines, these training programs have not been able to mitigate postflight alterations in postural and locomotor function. Therefore, the goal of our two inter-related projects (NSBRI-ground based and ISS flight study, "Mobility") is to develop and test gait training programs that will serve to optimize functional mobility during the adaptation period immediately following space flight, thereby improving the safety and efficiency of planetary ambulation. The gait training program entails manipulating the sensory conditions of treadmill exercise to systematically challenge the balance and gait control system. This enhances the overall adaptability of locomotor function enabling rapid reorganization of gait control to respond to ambulation in different gravitational environments. To develop the training program, we are conducting a series of ground-based studies evaluating the training efficacy associated with variation in visual flow, body loading, and support surface stability during treadmill walking. We will also determine the optimal method to present training stimuli within and across training sessions to maximize both the efficacy and efficiency of the training procedure. Results indicate that variations in both visual flow and body unloading during treadmill walking leads to modification in locomotor control and can be used as effective training modalities. Additionally, the composition and timing of sensory challenges experienced during each training session has significant impact on the ability to rapidly reorganize locomotor function when exposed to a novel sensory environment. We have developed the capability of producing support surface variation during gait training by mounting a treadmill on a six-degree-of-freedom motion device. This hardware development will allow us to evaluate the efficacy of this type of training in conjunction with variation in visual flow and body unloading

HCV-associated mixed cryoglobulinemia and b-cell non-Hodgkin's lymphoma - pathogenetically related problems

Hepatitis C virus (HCV) is a global population problem due to its high prevalence, usually late diagnosis, the difficulties of treatment. In the prognosis of patients with HCV not only hepatic, but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (CG), are important. Mixed CG is currently considered as a B-cell benign lymphoproliferative disorders. The role of HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin’s lymphoma (NHL). The purpose of the review was to provide an overview of recent literature data and the meta-analysis of epidemiological data explaining the role of HCV in the development of NHL. The review also discusses the treatment for HCV-associated NHL by antiviral therapy or other therapeutic options, such as chemotherapy

Перспективы применения белимумаба при волчаночном нефрите

Over the past 50 years the survival rate of patients with systemic lupus erythematosus (SLE) significantly improved, however, it is necessary to develop a new generation of drugs for the treatment of lupus nephritis (LN), the development of which is one of the main factors of high mortality risk in at least 50% of SLE patients. The international clinical trial BLISS-LN has demonstrated a high rate of achievement and maintenance of renal response (RR), confirmed by a higher rate of achievement of RR primary efficacy and complete renal response when using belimumab (BLM) in addition to standard therapy (ST) compared to ST alone in patients with LN. When using BLM, there was a statistically significant reduction in the risk of developing adverse renal events (in particular, deterioration of renal function) or death within 104 weeks compared with placebo. Improvement in LN outcomes was achieved in the setting of long-term reduction in glucocorticoids use after the induction phase. With BLM therapy, there was also a decrease in the total activity of SLE, a decrease in the number of severe exacerbations, and an improvement in serological markers. The benefit/risk ratio of BLM in combination with ST for LN treatment was favorable. BLM can be recommended for LN therapy in combination with standard treatment methods in order to achieve and maintain remission.За последние 50 лет удалось существенно улучшить выживаемость больных системной красной волчанкой (СКВ), однако необходимо создание нового поколения препаратов для терапии волчаночного нефрита (ВН), развитие которого не менее чем у 50% больных СКВ является одним из основных факторов высокого риска летальности. Международное клиническое исследование BLISS-LN продемонстрировало высокую частоту достижения и сохранения почечного ответа (ПО), подтвержденную более высокой частотой достижения ПО первичной эффективности и полного почечного ответа при применении белимумаба (БЛМ) в дополнение к стандартной терапии (СТ) по сравнению с одной СТ у пациентов с волчаночным нефритом (ВН). При применении БЛМ наблюдалось статистически значимое снижение риска развития нежелательных явлений со стороны почек (в частности, ухудшения функции почек) или смертельного исхода в течение 104 нед по сравнению с плацебо. Улучшение исходов ВН было достигнуто в условиях долгосрочного уменьшения применения глюкокортикоидов после индукционной фазы. При терапии БЛМ отмечалось также снижение общей активности СКВ, уменьшение числа тяжелых обострений и улучшение показателей серологических маркеров. Соотношение «польза/риск» при использовании БЛМ в сочетании со СТ для лечения ВН было благоприятным. БЛМ может быть рекомендован для терапии ВН в комбинации со стандартными методами лечения с целью достижения и поддержания ремиссии

Relationship between serologic profile (ANCA type) and clinical features of renal involvement in ANCA-associated vasculitides

Objective. To compare the frequency, clinical features and outcomes of renal involvement in ANCA-associated vasculitides (AAV) in patients with antibodies against proteinase-3 (pr3-ANCA) and myeloperoxidase (MPO-ANCA). Materials and methods. In our retrospective study we enrolled 264 patients, 94 males and 170 females, median age 53 [36; 62] years. Among them 157 were pr3-ANCA positive and 107 were MPO-ANCA positive. AAV was diagnosed according to ACR criteria and Chapel Hill consensus conference definition (2012). Median follow up was 44 [18; 93] months. We assessed baseline BVAS and VDI by the end of the follow up. Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and daily proteinuria were estimated. Diagnosis and stage of chronic kidney disease (CKD) and acute kidney injury (AKI) were established according to KDIGO guidelines (2012) and Scientific Society of Russian Nephrologists (2016). Results. Renal involvement was present in 181 (68.6%) patients, and its frequency was similar in pr3-ANCA and MPO-ANCA subgroups. Patients with MPO-ANCA developed rapidly progressive glomerulonephritis and hypertension significantly more often than patients with pr3-ANCA: 50.7% vs 35.6% (p=0.049) and 46.1% vs 29.8% (p=0.029) respectively. At disease onset, median sCr was significantly higher and eGFR was significantly lower in patients with MPO-ANCA (

Preclinical studies of antiviral activity of the RPH-137 fusion protein and molnupiravir against COVID-19

Finding effective and safe medicines to fight SARS-CoV-2 infection is an urgent task. RPH-137 is an original trap fusion protein against SARS-CoV-2 virus. It comprises the angiotensin-converting enzyme type 2 extracellular domain and the human IgG1 Fc fragment.The aim of the study was to carry out a preclinical evaluation of the efficacy of RPH-137 and molnupiravir against SARS-CoV-2 infection.Materials and methods: the authors analysed RPH-137 expressed in a stable CHO cell line and molnupiravir used as an active pharmaceutical ingredient. Drug-mediated inhibition of virus-induced cytotoxicity was assessed in Vero cell culture. In vivo efficacy assessments were performed in Syrian hamsters. The animals were infected intranasally with SARS-CoV-2 (PIK35 clinical isolate) in the dose of 5 log TCID50. The authors evaluated body weight measurements, lung–body weight ratios, and lung histopathology findings and determined viral RNA levels in oropharyngeal swabs by RT-PCR using the amplification cycle threshold (Ct). The statistical analyses involved one- and two-way ANOVA, Student's t-test, and Mann–Whitney test.Results: RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells; the EC50 values of RPH-137 amounted to 4.69 μg/mL (21.3 nM) and 16.24 μg/mL (73.8 nM) for 50 TCID50 and 200 TCID50, respectively, whereas the EC50 values of molnupiravir were 0.63 μg/mL (1900 nM) for both doses. Intramuscular RPH-137 (30 and 80 mg/kg) had no effect on the infection process in Syrian hamsters. The comparison with the challenge control group showed that intraperitoneal RPH-137 (100 mg/kg) had statistically significant effects on a number of parameters, including a 27% reduction in inflammation and a 30% reduction in the total lesion area of the lungs by Day 7. Intragastric molnupiravir (300 mg/kg twice daily) significantly inhibited SARS-CoV-2 infection.Conclusions: both RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells. In Syrian hamsters, molnupiravir demonstrated a more pronounced inhibition of SARS-CoV-2 infection than RPH-137. However, RPH-137 had statistically significant effects on a range of parameters. This offers additional perspectives for further research

Macro- And microstructural changes in cosmonauts' brains after long-duration spaceflight

Long-duration spaceflight causes widespread physiological changes, although its effect on brain structure remains poorly understood. In this work, we acquired diffusion magnetic resonance imaging to investigate alterations of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) compositions in each voxel, before, shortly after, and 7 months after long-duration spaceflight. We found increased WM in the cerebellum after spaceflight, providing the first clear evidence of sensorimotor neuroplasticity. At the region of interest level, this increase persisted 7 months after return to Earth. We also observe a widespread redistribution of CSF, with concomitant changes in the voxel fractions of adjacent GM. We show that these GM changes are the result of morphological changes rather than net tissue loss, which remained unclear from previous studies. Our study provides evidence of spaceflight-induced neuroplasticity to adapt motor strategies in space and evidence of fluid shift- induced mechanical changes in the brain. © 2020The Authors, some rights reserved.Peer reviewe

Erratum to: Cortical reorganization in an astronaut’s brain after long-duration spaceflight (Brain Struct Funct, DOI 10.1007/s00429-015-1054-3)

peer reviewe

Обновленные рекомендации EULAR/ERA–EDTA 2019 г. по терапии волчаночного нефрита. Комментарии экспертов. Часть I

The paper presents the main provisions of the 2019 updated European League Against Rheumatism (EULAR)/European Renal Association (ERA) – European Dialysis and Transplant Association (EDTA) guidelines for the management of lupus nephritis. It discusses the technology of preparing recommendations by an international group of rheumatologists, nephrologists, morphologists, and pediatricians. The main part contains recommendations on the use of induction and maintenance therapy with immunosuppressants, glucocorticoids, and biological agents. The issues relating to the management of pregnant patients with end-stage renal failure are considered.Представлены основные положения обновленных рекомендаций EULAR/ ERA–EDTA 2019 г. по терапии волчаночного нефрита. Обсуждается технология подготовки рекомендаций международной группой ревматологов, нефрологов, морфологов и педиатров. В основной части содержатся рекомендации по применению индукционной и поддерживающей терапии с использованием иммуносупрессоров, глюкокортикоидов и генно-инженерных биологических препаратов. Рассмотрены вопросы ведения пациенток с беременностью и терминальной почечной недостаточностью