Крымский фактор в становлении общественного идеала Л. Украинки

В статье рассмотрено воздействие крымских впечатлений на процесс становлення общественного идеала выдающейся украинской поэтессы Леси Украинки преимущественно в первый период ее творчества.У статті розглянутий вплив кримських вражень на процес становлення суспільного ідеалу видатної української поетеси Лесі Українки переважно у перший період її творчості.In article is considered influence of the crimeam impressions on process of the formation of the public ideal of the prominent ukrainian poetess Lesi Ukrainki mainly at the first period her creative activity

Pelvic Girdle Reconstruction Based on Spinal Fusion and Ischial Screw Fixation in a Case of Aneurysmal Bone Cyst

A case of lytic lesion of the pelvis in a 23-year-old woman is presented. A biopsy led to the diagnosis aneurysmal bone cyst (ABC). Due to the histologically very aggressive growth of the tumor, a low malignant osteosarcoma could not be excluded. In an initial operation the tumour, affecting the sacrum, the iliac crest and the lower lumbar spine was resected. Temporary restabilisation of the pelvic ring was achieved by a titanium plate. The histological examination of the entire tumour confirmed the diagnosis ABC. After 6 months, the MRI showed no recurrence. The observed tilt of the spine to the operated side on the sacral base prompted a second surgical procedure: a transpedicular fixation of L5 and L4 was connected via bent titanium stems to the ischium, where the fixation was achieved by two screws. This construction allowed the correction of the base angle and yielded a stable closure of the pelvic ring. The patient has now been followed for 6 years: the bone grafts have been incorporated and, in spite of radiological signs of screw loosening in the ischium, the patient is fully rehabilitated and free of symptoms. Pedicle screws in the lower spine can be recommended for fixation of a pelvic ring discontinuity

About feasibility of SpaceX's human exploration Mars missionscenario with Starship

After decades where human spaceflight missions have been reserved to low Earth orbit, recentyears have seen mission proposals and even implemented plans, e.g. with the mission Artemis I, forreturning to the lunar surface. SpaceX has published over various media (e.g., its official website,conference presentations, user manual) conceptual information for its reusable Starship to enablehuman exploration missions to the Martian surface by the end of the decade. The technological andhuman challenges associated with these plans are daunting. Such a mission at that distance wouldrequire excellent system reliability and in-situ-resource utilization on a grand scale, e.g. to producepropellant. The plans contain little details however and have not yet been reviewed concerning theirfeasibility. In this paper we show significant technological gaps in these plans. Based on estimatesand extrapolated data, a mass model as needed to fulfill SpaceX’s plans could not be reproducedand the subsequent trajectory optimization showed that the current plans do not yield a returnflight opportunity, due to a too large system mass. Furthermore, significant gaps exist in relevanttechnologies, e.g. power supply for the Martian surface. It is unlikely that these gaps can be closeduntil the end of the decade. We recommend several remedies, e.g. stronger international participationto distribute technology development and thus improve feasibility. Overall, with the limitedinformation published by SpaceX about its system and mission scenario and extrapolation from us tofill information gaps, we were not able to find a feasible Mars mission scenario using Starship, evenwhen assuming optimal conditions such as 100% recovery rate of crew consumables during flight

Detection and phase I metabolism of the 7‐azaindole‐derived synthetic cannabinoid 5F‐AB‐P7AICA including a preliminary pharmacokinetic evaluation

AbstractIn June 2018, a 'research chemica'l labeled 'AB‐FUB7AICA' was purchased online and analytically identified as 5F‐AB‐P7AICA, the 7‐azaindole analog of 5F‐AB‐PINACA. Here we present data on structural characterization, suitable urinary consumption markers, and preliminary pharmacokinetic data. Structure characterization was performed by nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry, infrared and Raman spectroscopy. Phase I metabolites were generated by applying a pooled human liver microsome assay (pHLM) to confirm the analysis results of authentic urine samples collected after oral self‐administration of 2.5 mg 5F‐AB‐P7AICA. Analyses of pHLM and urine samples were performed by liquid chromatography−time‐of‐flight mass spectrometry and liquid chromatography–tandem mass spectrometry (LC–MS/MS). An LC–MS/MS method for the quantification of 5F‐AB‐P7AICA in serum was validated. Ten phase I metabolites were detected in human urine samples and confirmed in vitro. The main metabolites were formed by hydroxylation, amide hydrolysis, and hydrolytic defluorination, though – in contrast with most other synthetic cannabinoids – the parent compound showed the highest signals in most urine samples. The compound detection window was more than 45 hours in serum. The concentration‐time profile was best explained by a two‐phase pharmacokinetic model. 5F‐AB‐P7AICA was detected in urine samples until 65 hours post ingestion. Monitoring of metabolite M07, hydroxylated at the alkyl chain, next to parent 5F‐AB‐P7AICA, is recommended to confirm the uptake of 5F‐AB‐P7AICA in urinalysis. It seems plausible that the shift of the nitrogen atom from position 2 to 7 (e.g. 5F‐AB‐PINACA to 5F‐AB‐P7AICA) leads to a lower metabolic reactivity, which might be of general interest in medicinal chemistry

Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial

Purpose: To compare the effects of two arginine vasopressin (AVP) dose regimens on the hemodynamic response, catecholamine requirements, AVP plasma concentrations, organ function and adverse events in advanced vasodilatory shock. Methods: In this prospective, controlled, open-label trial, patients with vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery requiring norepinephrine >0.6μg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033IU/min (n=25) or 0.067IU/min (n=25). The hemodynamic response, catecholamine doses, laboratory and organ function variables as well as adverse events (decrease in cardiac index or platelet count, increase in liver enzymes or bilirubin) were recorded before, 1, 12, 24 and 48h after randomization. A linear mixed effects model was used for statistical analysis in order to account for drop-outs during the observation period. Results: Heart rate and norepinephrine requirements decreased while MAP increased in both groups. Patients receiving AVP at 0.067IU/min required less norepinephrine (P=0.006) than those infused with AVP at 0.033IU/min. Arterial lactate and base deficit decreased while arterial pH increased in both groups. During the observation period, AVP plasma levels increased in both groups (both P<0.001), but were higher in the 0.067IU/min group (P<0.001) and in patients on concomitant hydrocortisone. The rate of adverse events and intensive care unit mortality was comparable between groups (0.033IU/min, 52%; 0.067IU/min, 52%; P=1). Conclusions: A supplementary AVP infusion of 0.067IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033IU/mi

Mobile Air Quality Studies (MAQS) - an international project

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone

Monogenic variants in dystonia: an exome-wide sequencing study

Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222;excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations