miR-33a and Its Association with Lipid Profile in Patients with Carotid Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease with a complex, multifactorial pathogenesis, which includes lipid metabolism alterations. miR-33a is a microRNA that plays a key role in cholesterol efflux and promotes atherosclerosis, yet its relationship with lipid markers in carotid atherosclerosis (CA) remains unclear. The objective is to evaluate possible associations between miR-33a expression and lipid biomarkers in patients with CA. This was a prospective study that included 61 patients (median age 66.0 years, 55.7% male) with evidence of CA. Lipid profile (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol) was analyzed. Extraction and quantification of miR-33a-5p/3p was performed according to protocol. Patients were further divided depending on the target LDL level (<1.8 mmol/L). Patients with CA had relatively favorable LDL levels with a median of 2.0 mmol/L. Both miR-33a-5p and miR-33a-3p levels were lower in patients with less than targeted LDL levels (37.4 and 38.3 vs. 41.8 and 42.5 respectively, p < 0.05). A significant positive correlation between expression levels of miR-33a-5p/3p and degree of carotid stenosis was found (r = 0.44 and r = 0.38 respectively, p < 0.05). In a univariate linear regression model miR-33a-3p/5p was positively associated with LDL cholesterol (p = 0.02). miR-33a up-regulation is associated with CA and may, in fact, be a key player by targeting cholesterol metabolism. A decrease in LDL cholesterol (<1.8 mmol/L) corresponded to lower levels of miR-33a, yet the direction and causality of this association remains unclear.

Effects of isolation, crowding, and different psychological countermeasures on crew behavior and performance.

Studies conducted by I. Altman in the 1960-70s revealed the increase in the individual stress level under isolation and confinement. Altman introduced the term "privacy" as a desired level of personal space that humans need to feel psychologically comfortable. The author also mentioned the dynamic process of boundary regulation that can be accompanied by the increase in conflict tension in the confined groups. In our study with short-term chamber isolation ESKIS, we analyzed behavior, crew interactions, and psychological state of a mixed-gender crew with none or minimal previous isolation experience (4 males and 2 females) who spent 14 days in a small chamber of 50 m3. The study confirmed that the pre-isolation period was particularly stressful for the subjects who felt also significant anxiety during the first days of isolation. Also, some mood and sleep disturbances were detected under isolation and crowding. Psychological stress made the crew more cohesive; they demonstrated the increase in common values. Extraverted subjects who could obtain social support from their partners and Mission Control's duty teams were less interested in psychological support via VR.

Applications of methods of psychological support developed for astronauts for use in medical settings.

Over the past 40 years, psychological support (PS) for cosmonauts and astronauts has remained an important part of the regular biomedical provision of space crews during extended orbital flights. It includes well-developed principles and a set of methods that have proven its effectiveness for the maintenance of behavioral health under extreme conditions of space flight. The main principle of PS in flight is to restore the usual sensory input to compensate for the monotony and lack of external stimuli as a result of a long stay under isolation and confinement. Risk factors for the psychological health and well-being defined for the astronauts, such as sensory and social deprivation, monotony, confinement, and lack of privacy, also remain part and parcel of several civil professions. These include polar wintering, submarines, working on oil platforms, and ocean fishing. Most of these factors also adversely affect the recovery rate of a large contingent of medical institutions, especially bedridden patients with chronic diseases. Finally, due to the negative epidemiological situation associated with the spread of COVID-19, an increasingly wide range of citizens forced to be in self-isolation faces negative manifestations of the deprivation phenomena described previously. Several cases of successful use of PS under isolation, monotony, crowding, and confinement are presented. Thus, we assume that the use of psychological support methods developed for space flights could be extremely relevant in civil medicine and everyday life.

MicroRNA and Hemostasis Profile of Carotid Atherosclerosis.

Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and <60% (moderate). All patients underwent the following blood tests: general blood test, hemostatic parameters and microRNA. Extraction of microRNA was performed using Leukocyte RNA Purification Kit (NORGEN Biotec Corp., Thorold, ON, Canada); miRNA quantification was performed via RT-PCR. Statistical analysis was performed in R programming language (v. 4.1.0) using RSudio. MicroRNA expression profile was different depending on CA degree. MiR-33a-5p/3p levels were higher in patients with ≥60% carotid stenosis (42.70 and 42.45 versus 38.50 and 38.50, respectively, p < 0.05). Almost complete separation can be visualized with the levels of miR-126-5p: 9.50 in the moderate CA group versus 5.25 in the advanced CA (p < 0.001). MiR-29-5p was higher in the moderate CA group: 28.60 [25.50;33.05] than in advanced CA group: 25.75 [24.38;29.50] (p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p < 0.05); miR-21-5p with ADAMTS13, erythrocyte sedimentation rate and D-dimer (r = 0.42, r = 0.36 and r = 0.44, respectively, p < 0.05); stenosis degree with miR-33a-5p/3p and factor VIII levels (r = 0.43 (both) and r = 0.62, respectively, p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis.

Red Blood Cell Morphodynamics in Patients with Polycythemia Vera and Stroke.

Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p < 0.001) and γ-dis (100 (100; 140) vs. 140 (106; 188) s-1, p < 0.001) along with higher amplitude (10.1 (8.6; 12.2) vs. 7.7 (6.6; 9.2), p < 0.001) was seen in patients with PV compared with control. A statistically significant difference between PV patients with and without stroke in aggregation amplitude was found (p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke.

External Communication of Autonomous Crews Under Simulation of Interplanetary Missions.

Two experiments, with 17-day and 120-day isolation, were carried out within the frame of the Scientific International Research in Unique Terrestrial Station (SIRIUS) international project at the Institute of Biomedical Problems (Moscow, Russia). Manifestations of the "detachment" phenomenon in the crew - mission control center (MCC) communication previously identified in the Mars-500 project were confirmed in this study. As in the Mars-500 experiment, in the SIRIUS-19, the landing simulation in the halfway of isolation caused a temporary increase of crew communication with MCC. We also revealed several differences in the communication styles of male and female crew members. By the end of the experiment, there was a convergence of communication styles of all the SIRIUS crew members and also an increase in crew cohesion.

Neuropoly: An Educational Board Game to Facilitate Neurology Learning.

Introduction: Neurology is arguably one of the most difficult subjects to teach and study in the medical curriculum. Educational games (EG) may be a valid option to enhance motivation in neurology residents. Methods: We developed an educational board game (Neuropoly) to assist in teaching neurology. We present here an overview of the game, as well as the results of a pilot study aimed at determining: (a) the efficacy of the game in teaching certain neurological concepts; and (b) student compliance and satisfaction with the EG. Results: The pre- and post-play questionnaire scores differed significantly (3.2 ± 1.7 vs. 7.8 ± 1.6, p < 0.001). Our group of residents, showing an overwhelmingly positive response, very well received the game. The questions were rated as above average regarding difficulty. Conclusion: The "Neuropoly" educational board game has been shown to be interesting, efficient, and motivational among first- and second-year neurology residents. Novel educational methods for complex medical disciplines should be developed, with board games being a viable and inexpensive approach.

Role of Chiral Configuration in the Photoinduced Interaction of D- and L-Tryptophan with Optical Isomers of Ketoprofen in Linked Systems.

The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer's and Parkinson's diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor-acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole-dipole interaction in the secular equation.

Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders.

BACKGROUNDS AND PURPOSE: Philadelphia chromosome-negative myeloproliferative disorders (Ph-negative MPD) are a rare group of hematological diseases, including three distinct pathologies: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). They most often manifest with thrombotic complications, including cerebrovascular events. Covert brain infarcts (CBIs) are defin ed as predominantly small ischemic cerebral lesions that are detected using magnetic resonance imaging (MRI) in the absence of clinical stroke events. The relationship between MPD and CBIs remains unclear. METHODS: Included in the study were 103 patients with the diagnosis of Ph-MPD (according to WHO 2016 criteria) (median age-47 (35; 54) years; 67% female). In total, 38 patients had ET, 42 had PV, and 23 had PMF. They underwent clinical examination, routine laboratory analyses (complete blood count), brain MRI, ultrasound carotid artery, flow-mediated dilatation (as a measure of endothelial dysfunction-FMD). RESULTS: Overall, 23 patients experienced an ischemic stroke (as per MRI and/or clinical history), of which 16 (15.5%) could be classified as CBIs. The rate of CBIs per MPD subtype was statistically non-significant between groups (p = 0.35): ET-13.2%, PV-21.4%, and PMF-8.7%. The major vascular risk factors, including arterial hypertension, carotid atherosclerosis, and prior venous thrombosis, were not associated with CBIs (p > 0.05). Age was significantly higher in patients with CBIs compared to patients without MRI ischemic lesions: 50 (43; 57) years vs. 36 (29; 48) (p = 0.002). The frequency of headaches was comparable between the two groups. CBIs were associated with endothelial dysfunction (OR - 0.71 (95% CI: 0.49-0.90; p = 0.02)) and higher hemoglobin levels (OR-1.21 (95% CI: 1.06-1.55); p =0.03). CONCLUSIONS: CBIs are common in patients with Ph-negative MPD. Arterial hypertension and carotid atherosclerosis were not associated with CBIs in this group of patients. The most significant factors in the development of CBIs were endothelial dysfunction (as measured by FMD) and high hemoglobin levels. Patients with Ph-negative MPD and CBIs were older and had more prevalent endothelial dysfunction.

Stereoselectivity of Electron and Energy Transfer in the Quenching of (S/R)-Ketoprofen-(S)-Tryptophan Dyad Excited State.

Photoinduced elementary processes in chiral linked systems, consisting of drugs and tryptophan (Trp) residues, attract considerable attention due to several aspects. First of all, these are models that allow one to trace the full and partial charge transfer underlying the binding of drugs to enzymes and receptors. On the other hand, Trp fluorescence is widely used to establish the structure and conformational mobility of proteins due to its high sensitivity to the microenvironment. Therefore, the study of mechanisms of Trp fluorescence quenching in various systems has both fundamental and practical interest. An analysis of the photo-chemically induced dynamic nuclear polarization (CIDNP) and Trp fluorescence quenching in (R/S)-ketoprofen-(S)-tryptophan ((S/R)-KP-(S)-Trp) dyad carried out in this work allowed us to trace the intramolecular reversible electron transfer (ET) and obtain evidence in favor of the resonance energy transfer (RET). The fraction of dyad's singlet excited state, quenched via ET, was shown to be 7.5 times greater for the (S,S)-diastereomer than for the (R,S) analog. At the same time, the ratio of the fluorescence quantum yields shows that quenching effectiveness of (S,S)-diastereomer to be 5.4 times lower than for the (R,S) analog. It means that the main mechanism of Trp fluorescence quenching in (S/R)-KP-(S)-Trp dyad is RET.

Spin effects as a tool to study photoinduced processes in (S/R)-ketoprofen-(S)-N-methylpyrrolidine dyads.

(S/R)-Ketoprofen (KP) is considered to be the strongest photosensitizer among nonsteroidal anti-inflammatory drugs. The photosensitizing reactions are caused by a substituted benzophenone chromophore. It produces various toxic effects through the formation of active paramagnetic intermediates and photoproducts able to attack biological substrates. Photoinduced transformations of KP have been extensively studied in order to identify paramagnetic intermediates. Considerable attention is also paid to photoinduced processes in dyads, where KP is linked with chiral partners, since such processes believed to model the binding of chiral drugs with enzymes and receptors. In the present study, the dyads containing (S)/(R)-KP covalently linked with (S)-N-methylpyrrolidine have been synthesized to examine the peculiarities of photoinduced electron transfer (ET) and hydrogen transfer (HT) in chiral systems. To detect short-lived paramagnetic intermediates, in dyad's excited triplet state, such as biradical zwitter ion (BZI) and neutral biradical (BR), spin chemistry methods [chemically induced dynamic nuclear polarization (CIDNP) and chemically induced dynamic electron polarization (CIDEP) in arbitrary magnetic fields], allowing indirect detection of transient paramagnetic particles by NMR, have been utilized. Both mentioned processes have been found to begin with the excitation of KP into the triplet state followed by the formation of BZI for ET and BR for HT, respectively. Products of stereoselective attachment of the N-methylpyrrolidine residue to the carbonyl carbon atom of KP occurring in both BZI and BR have been detected by NMR spectral analysis. The value of electronic exchange interaction in biradicals has been determined from the position of the characteristic maximum of hyperpolarization in the CIDNP magnetic field dependences.

Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease.

BACKGROUND: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD) and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph) myeloproliferative disorders (MPD) including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PM). MATERIALS AND METHODS: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years), those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years) and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years). RESULTS: In 79% (n = 81) of cases in the study group (with Ph-MPD), patients had chronic CVD, with the most frequently identified symptoms being asthenia (92%) and headache (72%). Headache in Ph-MPD patients was more frequently (86%) associated with PM, while in patients with PV and ET it was equally distributed (70%). Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21%) patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery) was severely impaired in all study groups (median 5% with normal cut-off at 10%), the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011). CONCLUSION: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension, atherosclerotic vascular disease, heart rhythm disorders) in 50% of cases. MPD, while remaining un- or underdiagnosed, presents a major concern in the cerebrovascular setting. A large number of thrombotic strokes occurring in patients with ET underline the necessity of early diagnostics and preventive therapy in these patients.

Comparison of outcomes of patients with acute coronary syndromes with and without atrial fibrillation.

Preexisting or new-onset atrial fibrillation (AF) commonly occurs in patients with an acute coronary syndrome (ACS). However, it is currently unknown if previous or new-onset AF confers different risks in these patients. To determine the prognostic significance of new-onset and previous AF in patients with ACS, we evaluated all patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events (GRACE) between April 1999 and September 2001. We compared clinical characteristics, management, and hospital outcomes in patients with ACS and new-onset and previous AF with those without AF. Of a total of 21,785 patients with ACS enrolled in GRACE, 1,700 (7.9%) had previous AF and 1,221 (6.2%) had new-onset AF. Patients with any AF were older, more likely to be women, had more co-morbid conditions, and worse hemodynamic status. Most in-hospital adverse events (reinfarction, shock, pulmonary edema, bleeding, stroke, and mortality) were significantly higher in patients with any AF than those without AF. Only new-onset AF (not previous AF) was an independent predictor of all adverse in-hospital outcomes. We conclude that compared with patients with ACS without any AF, previous and new-onset AF are associated with increased hospital morbidity and mortality. However, only new-onset AF is an independent predictor of in-hospital adverse events in patients with ACS.