Differential induction of C6 glioma apoptosis and autophagy by 3ß-hydroxysteroid-indolamine conjugates.

In a previous work, we reported the synthesis of four novel indole steroids and their effect on rat C6 glioma proliferation in vitro. The steroid derived from dehydroepiandrosterone and tryptamine (IS-1) was the most active (52 % inhibition at 10 µM), followed by one of the epimers derived from pregnenolone and tryptamine (IS-3, 36 % inhibition at 10 µM). By contrast, the steroid derived from estrone and tryptamine (IS-2) showed negligible activity at 10 µM. No necrosis, increase in intracellular calcium or ROS levels was observed. In this work, the effect of compounds on C6 glioma apoptosis and autophagy is examined by fluorimetry and fluorescent microscopy. The IS-3 epimers disrupt the mitochondrial membrane potential and induce apoptosis in vitro moderately whereas IS-1 and IS-2 do not. However, IS-1 produces a large increase in monodansylcadaverine-positive autophagic vesicles over 24 h. The antiproliferative effect of indole steroids is ameliorated by autophagy inhibitor hydroxychloroquine, suggesting an autophagy-dependent mechanism of cell death.

Russian nurses' readiness for transcultural care of palliative patients.

Palliative care involves an approach aimed at improving the quality of life of patients and their families, who are forced to cope with the problems associated with life-threatening diseases. This definition includes a growing group of patients around the world. It requires an extension of the definition of patients in need of palliative care in countries such as Russia and a significant improvement in the work of nursing personnel with these patients. This study aims to determine the level of preparedness of nursing personnel for specialized care (transcultural care) and the quality of care provided to palliative patients. The presented findings of the study demonstrate the relevance of developing transcultural competence, which enables significant improvement in the quality of life of palliative patients. The analysis of medical workers' assessment of the level of specific training and their intercultural preparedness was conducted based on hospices (Moscow). A survey was conducted among 113 medical workers of the middle level of education aged between 28 and 56 (average of 44.2 years) and experience in palliative care ranged from 3 to 18 years (average of 9.5 years). The Intercultural Readiness Check (IRC) test, widely used to assess nursing staff worldwide, was used for the survey to determine the level of readiness for transcultural care. A strong correlation was found between a number of the test scales and measures of participants' age and experience. The presented material demonstrates the realization of an interdisciplinary approach to the issues of specific training of nursing personnel in the field of "transcultural care" in providing palliative care to incurable patients.

Specific features of rational pharmacotherapy in elderly patients.

OBJECTIVE: It is well-known that finding an optimum medication at the correct dose for elderly patients is challenging for the practitioner. This study aimed to examine the main trends in prescribing medications for elderly patients and their compliance with the principles of rational pharmacotherapy, and to establish the main factors affecting adherence to treatment in these patients. METHODS: 956 records of outpatients over 60 years of age were examined. The groups of medications prescribed, the dosage simultaneously prescribed to one patient, the structure of nosologies among elderly patients, and the frequency of side effects were studied. The second stage of the study with 147 patients involved examining the adherence to medications by elderly patients using the Brief Medication Questionnaire. RESULTS: A total of 147 patients (79 (53.7%) women and 68 (46.3%) men) aged over 60 years who were taking ≥4 medications for primary and concomitant diseases were surveyed. The phenomenon of polypragmasy is clearly seen when prescribing pharmacotherapy to elderly patients. Thus, 39% of patients were prescribed 2-4 drugs simultaneously, 55.4% were prescribed ≥5 drugs, and only 5.6% were prescribed one type of medication. Consequently, 90.5% of patients did not comply with the prescribed regimen of drugs. The main reasons for low adherence to treatment were: the complexity of the drug regimen (72.1% of cases); the high cost of drugs (63.9%); lack of appropriate knowledge about disease (67.3%); and no understanding of the necessity for drug intake and the pharmacotherapeutic effect in a particular situation (61.9%). CONCLUSION: Optimisation of pharmacotherapy for elderly and senile patients requires consideration of functional changes in the body, the peculiarities of the pharmacodynamics and pharmacokinetics of drugs prescribed, the presence of polymorbidity, the prevalence of polypragmasy, and the low adherence to treatment.

Post-COVID worsening of a Parkinson's disease patient.

Worsening of clinical symptoms after COVID-19 infection and misregulation of CD4 and CD8 T-cell numbers may be revealed in PD patients. Immunological changes may be a source of clinical worsening of the patient.

One-Year Mission on ISS Is a Step Towards Interplanetary Missions.

BACKGROUND: in the 1990s Russian cosmonauts performed six long-duration missions on Mir that went from 312 to 438 d. In 2015 a mission on the International Space Station that continued for 340 d, 8 h, and 47 min was successfully accomplished. It was a joint U.S./Russian mission completed by Scott Kelly and Mikhail Kornienko (KM). METHODS: The intensity of in-flight physical exercises and postflight motor changes were measured in KM and in the six cosmonauts who made shorter flights (173.3 ± 13.8 d) on ISS while using similar countermeasures against the adverse effects of microgravity. RESULTS: It was found that both parameters varied similarly in spite of the difference in the duration of ISS missions. KM maintained adequate physical performance throughout the entire flight; moreover, the level of postflight changes he displayed was comparable to that recorded in the group of cosmonauts who completed 6-mo missions on ISS. DISCUSSION: In summary, the 1-yr mission has clearly demonstrated the high efficacy of the countermeasures used by KM.Fomina EV, Lysova NYu, Kukoba TB, Grishin AP, Kornienko MB. One-year mission on ISS is a step towards interplanetary missions. Aerosp Med Hum Perform. 2017; 88(12):1094-1099.

The effect of long-term confinement and the efficacy of exercise countermeasures on muscle strength during a simulated mission to Mars: data from the Mars500 study.

BACKGROUND: Isolation and long duration spaceflight are associated with musculoskeletal deconditioning. Mars500 was a unique, high-fidelity analogue of the psychological challenges of a 520-day manned mission to Mars. We aimed to explore the effect of musculoskeletal deconditioning on three outcome measures: (1) if lower limb muscle strength was reduced during the 520-day isolation; (2) if type I or II muscle fibres were differentially affected; and (3) whether any 70-day exercise interventions prevented any isolation-induced loss of strength. METHODS: Six healthy male subjects (mean ± SEM) (34 ± 3 years; 1.76 ± 0.02 metres; 83.7 ± 4.8 kg) provided written, informed consent to participate. The subjects' maximal voluntary contraction (MVC) was assessed isometrically in the calf (predominantly type I fibres), and maximal voluntary isokinetic force (MVIF) was assessed in the quadriceps/hamstrings (predominantly type II fibres) at 0.2 and 0.4 ms-1 using the Multifunctional Dynamometer for Space (MDS) at 35-day intervals throughout Mars500. Exercise interventions were completed 3-7 days/week throughout the 520-day isolation in a counterbalanced design excluding 142-177 days (rest period) and 251-284 days (simulated Mars landing). Exercise interventions included motorized treadmill running, non-motorized treadmill running, cycle ergometry, elastomer-based resistance exercise, whole-body vibration (WBV), and resistance exercise using MDS. RESULTS: Calf MVC did not reduce across the 520-day isolation and MDS increased strength by 18% compared to before that of 70-day exercise intervention. In contrast, there was a significant bilateral loss of MVIF across the 520 days at both 0.2 ms-1 (R 2 = 0.53; P = 0.001) and 0.4 ms-1 (0.4 ms-1; R 2 = 0.42; P = 0.007). WBV (+ 3.7 and 8.8%) and MDS (+ 4.9 and 5.2%) afforded the best protection against isolation-induced loss of MVIF, although MDS was the only intervention to prevent bilateral loss of calf MVC and leg MVIF at 0.2 and 0.4 ms-1. CONCLUSIONS: Mars500 induced significant loss of quadriceps/hamstrings MVIF but not calf MVC. Collectively, these data suggest that muscles with predominantly type I fibres were affected less by isolation compared to type II dominant muscles. MDS and WBV afforded the best protection against isolation-induced loss of strength and thus may have virtue in exploration class missions.

Locomotion Strategy and Magnitude of Ground Reaction Forces During Treadmill Training on ISS.

INTRODUCTION: Creation of the cosmonaut in-flight physical training process is currently based on the leading role of support afferents in the development of hypogravity changes in the motor system. We assume that the strength of support afferents is related to the magnitude of the ground reaction forces (GRF). For this purpose it was necessary to compare the GRF magnitude on the Russian BD-2 treadmill for different locomotion types (walking and running), modes (active and passive), and subjects. METHODS: Relative GRF values were analyzed while subjects performed walking and running during active and passive modes of treadmill belt movement under 1 G (N = 6) and 0 G (N = 4) conditions. RESULTS: For different BD-2 modes and both types of locomotion, maximum GRF values varied in both 0 G and 1 G. Considerable individual variations were also found in the locomotion strategies, as well as in maximum GRF values. In 0 G, the smallest GRF values were observed for walking in active mode, and the largest during running in passive mode. In 1 G, GRF values were higher during running than while walking, but the difference between active and passive modes was not observed; we assume this was due to the uniqueness of the GRF profile. DISCUSSION: The maximum GRF recorded during walking and running in active and passive modes depended on the individual pattern of locomotion. The maximum GRF values that we recorded on BD-2 were close to values found by other researchers. The observations from this study could guide individualized countermeasures prescriptions for microgravity.Fomina E, Savinkina A. Locomotion strategy and magnitude of ground reaction forces during treadmill training on ISS. Aerosp Med Hum Perform. 2017; 88(9):841-849.

Evolution of Russian Microgravity Countermeasures.

INTRODUCTION: Countermeasures to prevent or partially offset the negative physiologic changes that are caused by the effects of microgravity play an important role in supporting the performance of crewmembers in flight and their safe return to Earth. Research conducted in Russia on the orbital stations Salyut and Mir, as well as simulation experiments on the ground, have demonstrated that changes that occur during extended spaceflight in various physiologic systems can be prevented or significantly decreased by using countermeasures. Hardware and techniques used on the ISS have been substantially improved to reflect the experience of previous extended missions on Russian orbital stations. Countermeasures used during early ISS missions consisted of the U.S. treadmill (TVIS), cycle ergometer (ВБ-3), a set of resistance bands, a postural muscle loading suit (Penguin-3), electrical stimulator (Tonus-3), compression thigh cuffs (Braslet-М), a lower body negative pressure (LBNP) suit (Chibis), a lower body g-loading suit (Kentavr), and water/salt supplements. These countermeasures are described in this article.

Kidney function and urine protein composition in healthy volunteers during space station fitness tests.

BACKGROUND: There is a close physiological connection between muscular activity and kidney function. During physical exercise (PE) the qualitative and quantitative composition of urine changes. This paper explores the influence of moderate PE on urine protein composition. The study of urine protein composition will help to make corrections to the existing methods of countermeasures. METHODS: There were 10 healthy men who exercised on a treadmill similar to the one onboard the International Space Station. We analyzed their urinary proteome composition, potassium level, sodium level, and their level of osmotically active substances before and after PE. RESULTS: After moderate PE, a small increase in urine flow speed and a constant glomerular filtration rate were noted. The average-group index of total protein excretion within the urine was reliably increased. From the 148 proteins identified in the urine, 64 were associated with known tissue origin. We found that protein penetration into the urine had a positive correlation with their tissue expression. Selectivity of the glomerular barrier during PE decreased and high-molecular weight proteins penetrated through the glomerular barrier more easily after PE. DISCUSSION: Performance of moderate intensity physical exercise of short duration did not lead to an increase in the glomerular filtration rate nor did diuresis increase above the limits of baseline variability. However, the protein excretion rate increased after PE. We also observed that protein composition drift indicated a change in the set of biological processes in which a given protein participated, in some cases activating, in some cases inactivating them.

The U3 region of Moloney murine leukemia virus contains position-independent cis-acting sequences involved in the nuclear export of full-length viral transcripts.

The distinguishing feature of self-inactivating (SIN) retroviral vectors is the deletion of the enhancer/promoter sequences in the U3 region of the 3' long terminal repeat. This design is used to overcome transcriptional interference and prevent downstream transcription from the 3' long terminal repeat. SIN vectors were derived from a number of different retroviruses. Studies of SIN vectors show that extensive U3 deletions in HIV-based vectors do not alter viral titers or the in vitro and in vivo properties of the vectors. However, deletion of the U3 sequences in γ- and α-retroviruses correlates with defects in 3' RNA processing and reduces viral titers by >10-fold. Here, we studied the steps in the retroviral life cycle that are affected by the deletion of sequences in the 3' U3 region of Moloney murine leukemia virus-derived retroviral vectors. The results show that the amounts of both full-length and internal RNA transcripts of U3-minus vectors are reduced in the nuclei of transfected cells, an effect that is probably due to a general defect in 3' RNA processing. Furthermore, full-length RNA transcripts were also defective in terms of nuclear export. This defect was complemented by transferring the U3 region to another position within the retroviral vector, indicating that the U3 region contains position-independent cis-acting sequences that are required for the transport of full-length viral transcripts. The results also suggest that the leader region of Moloney murine leukemia virus contains inhibitory/regulatory sequences, which prevent export and mediate nuclear retention of full-length viral RNA.

Progressive adaptation in physical activity and neuromuscular performance during 520d confinement.

To understand whether prolonged confinement results in reductions in physical activity and adaptation in the musculoskeletal system, six subjects were measured during 520 d isolation in the Mars500 study. We tested the hypothesis that physical activity reduces in prolonged confinement and that this would be associated with decrements of neuromuscular performance. Physical activity, as measured by average acceleration of the body's center of mass ("activity temperature") using the actibelt® device, decreased progressively over the course of isolation (p<0.00001). Concurrently, countermovement jump power and single-leg hop force decreased during isolation (p<0.001) whilst grip force did not change (p≥0.14). Similar to other models of inactivity, greater decrements of neuromuscular performance occurred in the lower-limb than in the upper-limb. Subject motivational state increased non-significantly (p = 0.20) during isolation, suggesting reductions in lower-limb neuromuscular performance were unrelated to motivation. Overall, we conclude that prolonged confinement is a form of physical inactivity and is associated with adaptation in the neuromuscular system.

On the inclusion of alkanes into the monolayer of aliphatic alcohols at the water/alkane vapor interface: a quantum chemical approach.

In the framework of the quantum chemical semiempirical PM3 method thermodynamic and structural parameters of the formation and clusterization of aliphatic alcohols C(n)H(2n+1)OH (n(OH) = 8-16) at 298 K at the water/alkane vapor C(n)H(2n+2), (n(CH(3)) = 6-16) interface were calculated. The dependencies of enthalpy, entropy and Gibbs' energy of clusterization per one monomer molecule of 2D films on the alkyl chain length of corresponding alcohols and alkanes, the molar fraction of alkanes in the monolayers and the immersion degree of alcohol molecules into the water phase were shown to be linear or stepwise. The threshold of spontaneous clusterization of aliphatic alcohols at the water/alkane vapor interface was 10-11 carbon atoms at 298 K which is in line with experimental data at the air/water interface. It is shown that the presence of alkane vapor does not influence the process of alcohol monolayer formation. The structure of these monolayers is analogous to those obtained at the air/water interface in agreement with experimental data. The inclusion of alkane molecules into the amphiphilic monolayer at the water/alkane vapor interface is possible for amphiphiles with the spontaneous clusterization threshold at the air/water interface (n(s)(0)) of at least 16 methylene units in the alkyl chain, and it does not depend on the molar fraction of alkanes in the corresponding monolayer. The inclusion of alkanes from the vapor phase into the amphiphilic monolayer also requires that the difference between the alkyl chain lengths of alcohols and alkanes is not larger than n(s)(0) - 15 and n(s)(0) - 14 for the 2D film 1 and 2D film 2, respectively.

The influence of exercise on prefrontal cortex activity and cognitive performance during a simulated space flight to Mars (MARS500).

With respect to the plans of national and internationals space agencies to send people to Mars or Moon, long-term isolation studies are performed to learn about the psycho-physiological and psycho-social limitations of such missions. From June 3rd 2010 to November 4th 2011 six participants lived under totally isolated and confined conditions in the MARS500 habitat located in Moscow. Despite the possibility to mimic the condition of space travel, this study allowed for experimental conditions under very reliable and traceable conditions. As exercise is widely discussed to have a positive impact on neuro-cognitive performance, this study aimed to test the effect of different exercise protocol (endurance/strength orientated) on brain cortical activity and cognitive performance. Brain cortical activity was recorded using a 16 channel EEG before and after exercise across the 520 days of confinement. Cognitive performance was assessed using three commercially available brain games. Following the theory of transient hypofrontality, results show a significant decrease of frontal brain cortical activity after exercise (p<.05) which was most expressed after endurance orientated protocols. Cognitive performance was improved following running sessions on an active treadmill (p<.05). Results let us assume that not exercise per se acts as a neuro-enhancer. It is more likely that a general defocusing caused by an immersion into exercise is necessary to improve cognitive performance.