Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.

The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.

Cardiac Magnetic Resonance in Patients with Suspected Tachycardia-Induced Cardiomyopathy: The Impact of Late Gadolinium Enhancement and Epicardial Fat Tissue.

Tachycardia-induced cardiomyopathy (TIC) is a reversible subtype of dilated cardiomyopathy (DCM) resulting from sustained supraventricular or ventricular tachycardia and diagnosed by the normalization of left ventricular ejection fraction (LVEF) after stable sinus rhythm restoration. The aim of this study was to determine the contribution of cardiac magnetic resonance (CMR) to the differential diagnosis of TIC and DCM with persistent atrial arrythmias in patients hospitalized for the first time with heart failure (HF) with reduced LVEF of nonischemic origin. A total of 29 patients (age: 58.2 ± 16.9 years; males: 65.5%; average EF: 37.0 ± 9.5%) with persistent atrial tachyarrhythmia and first decompensation of HF without known coronary artery diseases were included in this study. The patients successfully underwent cardioversion and were observed for 30 days. The study population was divided into groups of responders (TIC patients; N = 16), which implies achieving FF > 50% or its increase > 10% in 30 days of TIC, and non-responders (N = 13). The increase in left ventricle (LV) volumes measured using CMR was significantly higher in the non-responder group when compared with the responders (114.8 mL ± 25.1 vs. 68.1 mL ± 10.5, respectively, p < 0.05). Non-responders also demonstrated decreased interventricular septum thickness (9.1 ± 0.8 vs.11.5 ± 1.3, respectively, p < 0.05). Late gadolinium enhancement (LGE) was observed in 12 patients (41.4%). The prevalence of LGE was increased in the non-responder group (25.0% vs. 65.1%, respectively, p = 0.046). Notably, a septal mid-wall LGE pattern was found exclusively in the non-responders. Epicardial adipose tissue thickness was decreased in the non-responder group versus the TIC patients. Conclusion: Patients with TIC were found to have smaller atrial and ventricular dimensions in comparison to patients with DCM. In addition, LGE was more common in DCM patients.

Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion.

We aimed to explore the effect of the 3-day dry immersion, a model of physical unloading, on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch soleus muscle of six healthy females. We registered that a marked reduction (25-34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence, it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Downregulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon, and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, and transcription regulators is largely determined by their mRNA concentration. These mRNAs revealed in our work may serve as putative targets for future studies aimed at developing approaches for the prevention of muscle deconditioning induced by disuse.NEW & NOTEWORTHY Three-day dry immersion (a model of physical unloading) substantially changes the transcriptomic profile in the human soleus muscle, a muscle with predominantly slow-twitch fibers and strong postural function; despite this, we found no effect on the muscle proteome (highly abundant proteins). Dry immersion markedly reduces ADP-stimulated respiration; this decline is not accompanied by a decrease in the content of mitochondrial proteins/respiratory enzymes, indicating the disruption in regulation of cellular respiration.

Mathematical Model of Antibiotic Resistance Determinants' Stability Under Space Flight Conditions.

Increasing antibiotic resistance (AR) poses dangers of treatment complications and even treatment failure to astronauts. An AR determinant is a gene of resistance carried by bacteria. This article considers the issue of the stability of AR determinants and the influence of manned spaceflight conditions on this characteristic. A phenomenological model has been developed that makes it possible to evaluate the integral value of the stability of determinants of AR in bacteria as a function of time. Based on experimental results obtained during implementation of the SALYUT 7 space program, the stability of determinants of AR in Escherichia coli strains isolated before and after a spaceflight in 16 astronauts was evaluated. In addition, an assessment was made of the integral value of the stability of determinants of AR in bacteria during in vitro experiments, both in spaceflight and terrestrial conditions, after preincubation in space. The calculation using the developed phenomenological model showed that the stability of AR determinants in E. coli bacteria isolated from astronauts before the spaceflight is 33% higher than after the flight. The in vitro experiment carried out on board the International Space Station showed the opposite situation-an increase in the stability of AR determinants by 33% in cultures that have been in space compared with terrestrial control. This indicates an additional influence on the stability of determinants and of the astronaut's immune system, as well as space conditions. The common result in these two types of studies is the experimental fact that the largest number of bacteria, in space conditions, had two determinants of AR. The importance of fighting bacteria with two determinants is that at least three different antibiotics are required to have an effect. This circumstance makes it possible to predict a possible strategy for the use of antibiotics in autonomous spaceflights.

The State of the Organs of the Female Reproductive System after a 5-Day "Dry" Immersion.

The impact of weightlessness on the female reproductive system remains poorly understood, although deep space exploration is impossible without the development of effective measures to protect women's health. The purpose of this work was to study the effect of a 5-day "dry" immersion on the state of the reproductive system of female subjects. On the fourth day of the menstrual cycle after immersion, we observed an increase in inhibin B of 35% (p < 0.05) and a decrease in luteinizing hormone of 12% (p < 0.05) and progesterone of 52% (p < 0.05) compared with the same day before immersion. The size of the uterus and the thickness of the endometrium did not change. On the ninth day of the menstrual cycle after immersion, the average diameters of the antral follicles and the dominant follicle were, respectively, 14% and 22% (p < 0.05) higher than before. The duration of the menstrual cycle did not change. The obtained results may indicate that the stay in the 5-day "dry" immersion, on the one hand, can stimulate the growth of the dominant follicle, but, on the other hand, can cause functional insufficiency of the corpus lutea.

Left Ventricular Diastolic Dysfunction Screening by a Smartphone-Case Based on Single Lead ECG.

Aims: To investigate the potential of a signal processed by smartphone-case based on single lead electrocardiogram (ECG) for left ventricular diastolic dysfunction (LVDD) determination as a screening method. Methods and Results: We included 446 subjects for sample learning and 259 patients for sample test aged 39 to 74 years for testing with 2D-echocardiography, tissue Doppler imaging and ECG using a smartphone-case based single lead ECG monitor for the assessment of LVDD. Spectral analysis of ECG signals (spECG) has been used in combination with advanced signal processing and artificial intelligence methods. Wavelengths slope, time intervals between waves, amplitudes at different points of the ECG complexes, energy of the ECG signal and asymmetry indices were analyzed. The QTc interval indicated significant diastolic dysfunction with a sensitivity of 78% and a specificity of 65%, a Tpeak parameter >590 ms with 63% and 58%, a T value off >695 ms with 63% and 74%, and QRSfi > 674 ms with 74% and 57%, respectively. A combination of the threshold values from all 4 parameters increased sensitivity to 86% and specificity to 70%, respectively (OR 11.7 [2.7-50.9], P < .001). Algorithm approbation have shown: Sensitivity-95.6%, Specificity-97.7%, Diagnostic accuracy-96.5% and Repeatability-98.8%. Conclusion: Our results indicate a great potential of a smartphone-case based on single lead ECG as novel screening tool for LVDD if spECG is used in combination with advanced signal processing and machine learning technologies.

New geographical and host records of bat fleas (Siphonaptera: Ischnopsyllidae) in Russia.

To better understand the distribution and host-parasite relationships, we explored 12 large regions of Russia and recorded new bat fleas (Insecta: Siphonaptera: Ischnopsyllidae) for Dagestan, Bashkiria, Mordovia, Khakassia and Buryatia Republics. Also we curate previously known data and registered new host-parasite associations for species belonging to genus Ischnopsyllus (Ischnopsyllus octactenus and I. variabilis ex Pipistrellus pygmaeus, I. intermedius ex Hypsugo savii, I. variabilis ex Myotis dasycneme, I. hexactenus ex Murina hilgendorfi) and species Myodopsylla trisellis. One of the associations we recorded in Altai republic is particularly interesting (Myodopsylla trisellis ­ Myotis blythii). Further investigation is required to study vector role of bat fleas and the effects of flea parasitism on their natural hosts.

Investigation of Nitrogen and Vacancy Defects in Synthetic Diamond Plates by Positron Annihilation Spectroscopy.

Currently, diamonds are widely used in science and technology. However, the properties of diamonds due to their defects are not fully understood. In addition to optical methods, positron annihilation spectroscopy (PAS) can be successfully used to study defects in diamonds. Positrons are capable of detecting vacancies, and small and large clusters of vacancies induced by irradiation, by providing information about their size, concentration, and chemical environment. By mapping in the infrared (IR) range, it is possible to consider the admixture composition of the main inclusions of the whole plate. This article presents the results of a study of defects in synthetic diamond plates, one of which was irradiated by electrons. It presents data about the distribution of the defect concentration obtained by Infrared spectroscopy. PAS with a monochromatic positron beam can be used as a non-destructive technique of detecting defects (vacancy) distribution over the depth of diamond plates.

How We Perform a David Procedure With an Upper Hemisternotomy Approach.

OBJECTIVE: Valve-sparing aortic root replacement (David procedure) is the technique of choice in appropriately selected patients with aortic root aneurysms. These procedures are seldom performed in a minimally invasive fashion. We describe our systematic approach to the David procedure using an upper hemisternotomy (UHS). Methods: Our method involves a J-type UHS exiting the right third or fourth intercostal space. Ascending aortic and femoral venous cannulation are performed using the Seldinger technique under transesophageal echocardiographic guidance. Between August 2005 and August 2014, 27 patients underwent an isolated elective David procedure using a full sternotomy (FS). Sixteen underwent an isolated elective UHS David procedure from May 2015 to February 2019. Perioperative safety outcomes were compared between the 2 cohorts. Results: The UHS and FS David cohorts were primarily male (87.5% and 85.2%, respectively) and 51 and 50 years old on average, respectively. Custodiol-histidine-tryptophan-ketoglutarate cardioplegia (93.8% vs 37.0%, P < 0.001) and Cor-Knot (100% vs 0%, P < 0.001) were used significantly more in the UHS David cohort. There were no significant differences in cardiopulmonary bypass (200 [183-208] vs 212 [183-223] min, P = 0.309) and aortic cross-clamp (169 [155-179] vs 188 [155-199] min, P = 0.128) times in the UHS and FS cohorts. There were no instances of hospital or 30-day mortality in either cohort. Intensive care unit and hospital stays were comparable between the 2 cohorts. Conclusions: The David procedure via UHS is a safe and reproducible technique for aortic root replacement.

Sleep in 21-Day Dry Immersion. Are Cardiovascular Adjustments Rapid Eye Movement Sleep-Dependent?

Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system. Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring. Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP). Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.

The First Female Dry Immersion (NAIAD-2020): Design and Specifics of a 3-Day Study.

This article describes procedures and some results of the first study of females undergoing 3-day Dry Immersion. The experiment "NAIAD-2020" was carried out at the Institute of Biomedical Problems (Moscow, Russia) with the participation of six healthy women volunteers (age 30.17 ± 5.5 years, height 1.66 ± 0.1 m, weight 62.05 ± 8.4 kg, BMI 22.39 ± 2.2 kg/m2) with a natural menstrual cycle. During the study, a standard protocol was used, the same as for men, with a minimum period of time spent outside the immersion bath. Before, during and after Immersion, 22 experiments were carried out aimed at studying the neurophysiological, functional, metabolic and psychophysiological functions of the body, the results of which will be presented in future publications. The total time outside the bath for women did not exceed that for men. Systolic and diastolic pressure did not significantly change during the immersion. In the first 24 h after the end of the immersion, heart rate was significantly higher than the background values [F(4,20) = 14.67; P < 0.0001]. Changes in body temperature and water balance were consistent with the patterns found in men. No significant changes in height and weight were found during immersion. All women reported general discomfort and pain in the abdomen and back. The results of this study did not find significant risks to women's health and showed the feasibility of using this model of the effects of space flight in women of reproductive age.

New findings of spinturnicid mites (Mesostigmata: Gamasina: Spinturnicidae) from the Caucasus.

The Caucasus is a large region in Eurasia consisting of four countries: Russia, Georgia, Azerbaijan, and Armenia. Although it is one of the biodiversity hotspots in the world, the bat ectoparasite fauna has been poorly studied. To promotionally fill in the gaps regarding bat ectoparasites, we conducted five field surveys on bats and their ectoparasites at nine localities within the region between April 2016 and March 2021. Eight species and subspecies of spinturnicid mites were recorded over the surveys: Eyndhovenia euryalis oudemansi, Spinturnix acuminata acuminata, S. emarginata, S. myoti, S. nobleti, S. plecotina, S. psi, and S. punctata. Among them, three species, Spinturnix emarginata, S. nobleti and S. punctate, are newly recorded from the Caucasus region, and one each of subspecies and species, Eyndhovenia euryalis oudemansi and S. plecotina, are newly recorded from Georgia. In addition, Myotis tschuliensis was recorded as a new host species of S. myoti.

New records of bat flies (Diptera: Nycteribiidae), with an updated checklist of the nycteribiids of Russia.

We assembled a checklist by documenting and curating previously published data as well as previously unpublished records of bat flies from the Russian Federation. A total of 20 bat fly species are listed, belonging to 4 genera. Basilia mongolensis nudior Hurka, 1972 and Basilia nattereri (Kolenati, 1857) are recorded from Russia for the first time. The following new host associations are reported: Basilia mongolensis nudior ex Myotis nattereri (Kuhl), Basilia nattereri ex Eptesicus nilssonii (Keyserling Blasius), Basilia rybini Hurka, 1969 ex Myotis dasycneme (Boie) and Eptesicus nilssonii, and Nycteribia quasiocellata Theodor, 1966 ex Vespertilio murinus Linnaeus. We provide data on nine major Russian regions for which nycteribiid records were previously lacking.

Urinary shedding of leptospires in palearctic bats.

Leptospirosis is a bacterial zoonotic infection of worldwide occurrence. Bats, like other mammalian reservoirs, may be long-term carriers that maintain endemicity of infection and shed viable leptospires in urine. Direct and/or indirect contact with these Leptospira shedders is the main risk factor as regards public health concern. However, knowledge about bat leptospirosis in the Palearctic Region, and in Europe in particular, is poor. We collected urine from 176 specimens of 11 bat species in the Czech Republic, Poland, Republic of Armenia and the Altai Region of Russia between 2014 and 2019. We extracted DNA from the urine samples to detect Leptospira spp. shedders using PCR amplification of the 16S rRNA and LipL32 genes. Four bat species (Barbastella barbastellus n = 1, Myotis bechsteinii n = 1, Myotis myotis n = 24 and Myotis nattereri n = 1) tested positive for Leptospira spp., with detected amplicons showing 100% genetic identity with pathogenic Leptospira interrogans. The site- and species-specific prevalence range was 0%-24.1% and 0%-20%, respectively. All bats sampled in the Republic of Armenia and Russia were negative. Given the circulation of pathogenic leptospires in strictly protected Palearctic bat species and their populations, non-invasive and non-lethal sampling of urine for molecular Leptospira spp. detection is recommended as a suitable surveillance and monitoring strategy. Moreover, our results should raise awareness of this potential disease risk among health professionals, veterinarians, chiropterologists and wildlife rescue workers handling bats, as well as speleologists and persons cleaning premises following bat infestation.

Charge transport mechanism in the forming-free memristor based on silicon nitride.

Nonstoichiometric silicon nitride SiNx is a promising material for developing a new generation of high-speed, reliable flash memory device based on the resistive effect. The advantage of silicon nitride over other dielectrics is its compatibility with the silicon technology. In the present work, a silicon nitride-based memristor deposited by the plasma-enhanced chemical vapor deposition method was studied. To develop a memristor based on silicon nitride, it is necessary to understand the charge transport mechanisms in all states. In the present work, it was established that the charge transport in high-resistance states is not described by the Frenkel effect model of Coulomb isolated trap ionization, Hill-Adachi model of overlapping Coulomb potentials, Makram-Ebeid and Lannoo model of multiphonon isolated trap ionization, Nasyrov-Gritsenko model of phonon-assisted tunneling between traps, Shklovskii-Efros percolation model, Schottky model and the thermally assisted tunneling mechanisms. It is established that, in the initial state, low-resistance state, intermediate-resistance state and high-resistance state, the charge transport in the forming-free SiNx-based memristor is described by the space charge limited current model. The trap parameters responsible for the charge transport in various memristor states are determined.

Transcatheter and ministernotomy aortic valve replacement after bioprosthetic valve failure.

BACKGROUND: Transcatheter valve-in-valve implantation (TViV) and minimally invasive reoperative aortic valve replacement (MIrAVR) have rapidly increased as alternatives to conventional reoperative surgical AVR. This study reports a single-center experience of patients undergoing TViV and MIrAVR after bioprosthetic valve failure. METHODS: In this retrospective review between March 2009 and October 2018, 68 patients without reoperative full sternotomies, concomitant procedures, active endocarditis, and prior homografts or coronary artery bypass grafting underwent isolated AVR for degenerated aortic bioprostheses. Society of Thoracic Surgeons (STS) risk scores and age are reported as median (interquartile range [IQR]) and length of stay is reported as mean (standard deviation [SD]) due to their characteristics of the distribution. RESULTS: Forty-one (60.3%) patients underwent TViV, and 27 (39.7%) patients underwent MIrAVR. Median [IQR] STS risk scores were 5.7 [4.0-7.8] and 2.0 [1.5-3.4] for TViV and MIrAVR, respectively (p ≤ .001). The median [IQR] age for TViV patients was higher (78 [71-84] vs. 66 [53-72] years, p ≤ 0.001). More permanent pacemakers were implanted (22.2% vs. 9.8%) following MIrAVR. The MIrAVR group had a higher rate of atrial fibrillation (18.5% vs. 9.8%, p = .466). Average (SD) length of stay was less in TViV (5.3 days, SD: 3.4 vs. 8.6 days, SD: 7.4, p = .001). Survival at 1 year was not significantly different for TViV and MIrAVR (94.9% [95% confidence interval [CI]: 81.0%, 98.7%] and 86.9% [95% CI: 64.0%, 95.7%], respectively [p = .969]). CONCLUSIONS: Despite being at higher-risk, patients undergoing TViV had reduced rates of permanent pacemaker implantations and atrial fibrillation, and a shorter hospital stay as compared to MIrAVR. Survival at 1-year was similar between the two groups.

Active surveillance for antibodies confirms circulation of lyssaviruses in Palearctic bats.

BACKGROUND: Palearctic bats host a diversity of lyssaviruses, though not the classical rabies virus (RABV). As surveillance for bat rabies over the Palearctic area covering Central and Eastern Europe and Siberian regions of Russia has been irregular, we lack data on geographic and seasonal patterns of the infection. RESULTS: To address this, we undertook serological testing, using non-lethally sampled blood, on 1027 bats of 25 species in Bulgaria, the Czech Republic, Poland, Russia and Slovenia between 2014 and 2018. The indirect enzyme-linked immunosorbent assay (ELISA) detected rabies virus anti-glycoprotein antibodies in 33 bats, giving an overall seroprevalence of 3.2%. Bat species exceeding the seroconversion threshold included Myotis blythii, Myotis gracilis, Myotis petax, Myotis myotis, Murina hilgendorfi, Rhinolophus ferrumequinum and Vespertilio murinus. While Myotis species (84.8%) and adult females (48.5%) dominated in seropositive bats, juveniles of both sexes showed no difference in seroprevalence. Higher numbers tested positive when sampled during the active season (10.5%), as compared with the hibernation period (0.9%). Bat rabies seroprevalence was significantly higher in natural habitats (4.0%) compared with synanthropic roosts (1.2%). Importantly, in 2018, we recorded 73.1% seroprevalence in a cave containing a M. blythii maternity colony in the Altai Krai of Russia. CONCLUSIONS: Identification of such "hotspots" of non-RABV lyssavirus circulation not only provides important information for public health protection, it can also guide research activities aimed at more in-depth bat rabies studies.

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.