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Background: This study presents the findings of a newborn screening (NBS) pilot project for 5q-spinal muscular atrophy (5q-SMA) in multiple regions across Russia for during the year 2022. The aim was to assess the feasibility and reproducibility of NBS for SMA5q in diverse populations and estimate the real prevalence of 5q-SMA in Russia as well as the distribution of patients with different number of SMN2 copies., Methods: The pilot project of NBS here was based on data, involving the analysis of 202,908 newborns. SMA screening assay was performed using a commercially available real-time polymerase chain reaction kit, the Eonis SCID-SMA., Results: In one year, 202,908 newborns were screened, identifying 26 infants with homozygous deletion of SMN1 exon 7, yielding an estimated 5q-SMA incidence of 1:7804 newborns. It was found that 38.46% had two SMN2 copies, 42.31% had three copies, 15.38% had four copies, and 3.85% had five copies of SMN2. Immediate treatment was proposed for patients with two or three SMN2 copies. Infants with four or more SMN2 copies warranted further investigation on management and treatment. Short-term monitoring after gene therapy showed motor function improvements. Delays in treatment initiation were observed, including the testing for adeno-associated virus 9 antibodies and nonmedical factors., Conclusions: The study emphasizes the need for a standardized algorithm for early diagnosis and management through NBS to benefit affected families. Overall, the NBS program for 5q-SMA in Russia demonstrated the potential to improve outcomes and transform SMA from a devastating disease to a chronic condition with evolving medical requirements., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrey V. Marakhonov reports equipment, drugs, or supplies was provided by Novartis Pharma LLC. Andrey V. Marakhonov reports equipment, drugs, or supplies was provided by Skopinfarm LLC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study, conducted in the Republic of North Ossetia-Alania (RNOA), aimed to explore the genetic landscape of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) in the Ossetian population using data from newborn screening (NBS). Through comprehensive molecular genetic analysis of 29 patients with HPA from diverse ethnic backgrounds, two major genetic variants in the PAH gene, P281L and P211T, were identified, constituting 50% of all detected pathogenic alleles in Ossetian patients. Remarkably, these variants exhibited an exceptionally high frequency in the Ossetian population, surpassing global prevalence rates. This study unveiled a notable prevalence of mild forms of HPA (78%), underscoring the importance of genetic counseling for carriers of pathogenic variants in the PAH gene. Moreover, the findings emphasized the necessity for ongoing monitoring of patients with mild forms, as they may lack significant symptoms for diagnosis, potentially impacting offspring. Overall, this research offers valuable insights into the genetic landscape of HPA and PKU in the Ossetian population.

Newborn screening (NBS) for severe inborn errors of immunity (IEI), affecting T lymphocytes, and implementing measurements of T cell receptor excision circles (TREC) has been shown to be effective in early diagnosis and improved prognosis of patients with these genetic disorders. Few studies conducted on smaller groups of newborns report results of NBS that also include measurement of kappa-deleting recombination excision circles (KREC) for IEI affecting B lymphocytes. A pilot NBS study utilizing TREC/KREC detection was conducted on 202,908 infants born in 8 regions of Russia over a 14-month period. One hundred thirty-four newborns (0.66‰) were NBS positive after the first test and subsequent retest, 41% of whom were born preterm. After lymphocyte subsets were assessed via flow cytometry, samples of 18 infants (0.09‰) were sent for whole exome sequencing. Confirmed genetic defects were consistent with autosomal recessive agammaglobulinemia in 1/18, severe combined immunodeficiency - in 7/18, 22q11.2DS syndrome - in 4/18, combined immunodeficiency - in 1/18 and trisomy 21 syndrome - in 1/18. Two patients in whom no genetic defect was found met criteria of (severe) combined immunodeficiency with syndromic features. Three patients appeared to have transient lymphopenia. Our findings demonstrate the value of implementing combined TREC/KREC NBS screening and inform the development of policies and guidelines for its integration into routine newborn screening programs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autosomal dominant hearing loss is represented by a large number of genetically determined forms. Over 50 genes associated with dominant nonsyndromic hearing impairments were described. Pathogenic variants in the CEACAM16 gene lead to the development of DFNA4B hearing loss. Currently, 8 pathogenic variants in this gene have been described. The objective of this study was to study the audiological and molecular genetic characteristics of a large family with CEACAM16-associated autosomal dominant nonsyndromic hearing loss. A detailed anamnesis was collected, and a comprehensive audiological examination was performed for 21 family members. Genetic testing was performed, including whole-genome sequencing for the proband's son and Sanger sequence analysis for the proband and for all available family members. In a large Russian family, including 5 generations, an autosomal dominant type of slowly progressing nonsyndromic late-onset hearing loss was observed. Eleven family members suffer from hearing impairment, which starts with tinnitus and threshold increase at high frequencies, since the age of 5-20 years. Hearing loss slowly progresses with age in each person and is similar to age-related hearing loss. We have detected the novel likely pathogenic variant с.419С>T (p.(Thr140Ile)) in exon 3 of the CEACAM16 gene, which segregates with late-onset nonsyndromic hearing loss in this family. The clinical data obtained in the examined family correspond with the phenotype in previously described cases. In general, the study widened the mutation spectrum of the gene, allowing to carry out medical genetic counseling and to answer the questions about the hearing impairment prognosis for future generations.

Cerebral aneurysms are diagnosed in 1-5% of people and cause 80-85% of subarachnoid hemorrhages (SAH). Aneurysmal hemorrhages are more common in people aged 30-50 years causing high socio-economic significance of this disease. Therefore, the outcomes of microsurgical clipping are an urgent problem in these patients., Objective: To evaluate the immediate and long-term results after microsurgical treatment of cerebral aneurysms in acute period of hemorrhage; to analyze functional results and long-term outcomes, including higher mental functions and return to previous work., Material and Methods: The study included 517 patients in acute period of subarachnoid hemorrhage between 2019 and 2022. Severity of hemorrhage was assessed using the Hunt-Hess scale while the Fisher scale was valuable to estimate dimensions of hemorrhage and predictions for vasospasm. All patients underwent microsurgical clipping of aneurysms. We assessed clinical status and outcomes immediately after microsurgical clipping, within 2 weeks, 1, 3, 6 and 12 months after surgery. The Modified Glasgow Outcome Scale, Modified Rankin Scale (mRS), EQ-5D-3L Quality of Life Questionnaire, Mini-Mental State Examination MMSE and Hamilton Anxiety Rating Scale were used., Results: After 1 month, mRS score 0 was observed in 22% of patients, score 1 - 17%, score 2 - 19.4%, score 3 - 6.2%, score 4 - 2.6%, score 5 - 1% of patients. Mortality rate was 6.4%. After 12 months, mRS score 0, 1, 2, 3 and 4 was observed in 67%, 15%, 8%, 3% and 0.4% of patients, respectively. After 12 months, 39 (8.3%) patients did not return to previous work. Among 427 (91.7%) patients who returned to previous work, 20% returned to work after 3 months, 65% after 6 months and 15% after 9 months., Conclusion: Short-term and long-term functional outcomes vary significantly. There were significantly better mRS scores in long-term period compared to early period. Analysis of immediate and long-term results after hemorrhage will allow us to determine the most important predictors of adverse functional outcomes, assess the prevalence, characteristics, modifiable risk factors and consequences of hemorrhage.

A male factor, commonly associated with poor semen quality, is revealed in about 50% of infertile couples. CFTR gene (Cystic Fibrosis Transmembrane Conduction Regulator) variants are one of the common genetic causes of azoospermia-related male infertility. Notably, the spectrum and frequency of pathogenic CFTR variants vary between populations and geographical regions. In this work, we made an attempt to evaluate the allele frequency (AF) of 12 common CFTR variants in infertile Russian men and healthy individuals from different districts of Russia. Because of the limited number of population-based studies on Russian individuals, we characterized the population AFs based on data from the Registry of Russian cystic fibrosis (CF) patients. In addition to the CF patient registry, we estimated the local frequencies of the same set of variants based on the results of genotyping of CF patients in local biocollections (from St. Petersburg and Yugra regions). AFs of common CFTR variants calculated based on registry and biocollection data showed good concordance with directly measured population AFs. The estimated region-specific frequencies of CFTR variants allowed us to uncover statistically significant regional differences in the frequencies of the F508del (c.1521_1523del; p.Phe508del) and CFTRdele2,3(21kb) (c.54-5940_273+10250del21kb; p.Ser18ArgfsX) variants. The data from population-based studies confirmed previous observations that F508del, CFTRdele2,3(21kb), and L138ins (c.413_415dup; p.Leu138dup)variants are the most abundant among infertile patients, and their frequencies are significantly lower in healthy individuals and should be taken into account during genetic monitoring of the reproductive health of Russian individuals.

Inherited retinal diseases (IRDs) constitute a prevalent group of inherited ocular disorders characterized by marked genetic diversity alongside moderate clinical variability. Among these, ABCA4 -related eye pathology stands as a prominent form affecting the retina. In this study, we conducted an in-depth analysis of 96 patients harboring ABCA4 variants in the European part of Russia. Notably, the complex allele c.[1622T>C;3113C>T] (p.Leu541Pro;Ala1038Val, or L541P;A1038V) and the variant c.5882G>A (p.Gly1961Glu or G1961E) emerged as primary contributors to this ocular pathology within this population. Additionally, we elucidated distinct disease progression characteristics associated with the G1961E variant. Furthermore, our investigation revealed that patients with loss-of-function variants in ABCA4 were more inclined to develop phenotypes distinct from Stargardt disease. These findings provide crucial insights into the genetic and clinical landscape of ABCA4 -related retinal dystrophies in this specific population.

Ectodermal dysplasia (ED) is a heterogeneous group of hereditary diseases of the skin and its appendages, which are characterized by impaired development and/or homeostasis of two or more ectoderm derivatives, including: hair, teeth, nails, sweat glands and their modifications (mammary glands, for instance). The overall prevalence of ectodermal dysplasia remains precisely unknown not only in Russia, but also in the world, nor is known the contribution of individual genes to its structure. This complicates the DNA diagnosis establishment of this disease due to the lack of an accurate diagnostic algorithm and a universal cost-effective method of analysis. To date, the most highly-researched genes involved in the development of anhydrous or hypohidrotic forms of ED are EDA, EDAR, EDARADD and WNT10A. The ectodysplasin A (EDA) gene is the cause of the most common X-linked form of ED, a gene from the Wnt family (WNT10A) is responsible for the autosomal recessive form of the disease, and two other genes (EDAR and EDARADD) can cause both autosomal recessive and autosomal dominant forms. This review provides the characteristics of the genes involved in ED, their mutation spectra, the level of their expression in human tissues, as well as the interrelation of the aforementioned genes. The domain structures of the corresponding proteins are considered, as well as the molecular genetic pathways in which they are involved. Animal models for studying this disorder are also taken into consideration. Due to the cross-species genes conservation, their mutations cause the disruption of the development of ectoderm derivatives not only in humans, but also in mice, cows, dogs, and even fish. It can be exploited for a better understanding of the etiopathogenesis of ectodermal dysplasias. Moreover, this article brings up the possibility of recurrent mutations in the EDA and WNT10A genes. The review also presents data on promising approaches for intrauterine ED treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

Background and Importance: The supraorbital "keyhole" approach has been described for the treatment of basilar artery aneurysms. Transpalpebral approach (TPA) is an alternative minimally invasive route to aneurysms of the Circle of Willis with excellent functional and cosmetic outcomes., Clinical Presentation: 53-years-old female who presented with an incidentally found 6.3 mm BA aneurysm with 3.1 mm neck diameter, admitted to our department of neurovascular surgery. Clipping was performed through TPA, with endoscope assistance and intraoperative ICG angiography. The patient's postoperative course was uneventful and was discharged home on postoperative day 5 without any complications., Conclusion: First time in the literature described keyhole TPA with eyelid incision to BA aneurysm. TPA is technically difficult and requires some experience to work through deep and limited surgical corridor. This technique can be good alternative to traditional fronto-lateral, supraorbital keyhole craniotomies.

We examined a cohort of 93 cystic fibrosis (CF) male patients who were pancreatic-sufficient (PS-CF; n=40) or pancreatic-insufficient (PI-CF; n = 53). Complex semen examination was performed, including standard semen analysis, quantitative karyological analysis (QKA) of immature germ cells (IGCs), transmission electronic microscopy (TEM), biochemical analysis, and sperm DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL) assay. Azoospermia was diagnosed in 83 (89.2%) patients. The other 10 (10.8%) patients were found to be nonazoospermic and showed various spermatological diagnoses (asthenozoospermia, n = 2; asthenoteratozoospermia, n = 3; oligoasthenozoospermia, n = 1; oligoasthenoteratozoospermia, n = 3; and normozoospermia, n = 1) with no specific morphological abnormalities. Oligospermia was detected in 89.2% azoospermic and 30.0% nonazoospermic patients. Low seminal pH (<7.0) was found in 74 (89.2%) of 83 azoospermic patients. Moderate leukocytospermia (2.0 × 10 6 -2.2 × 10 6 ml -1 ) was revealed in 2.4% azoospermic and 40.0% nonazoospermic semen samples. The signs of partial meiotic arrest at prophase I were found in 4 of 6 nonazoospermic patients examined by QKA of IGCs. The content of fructose and citrate was low in oligospermic and normal in nonoligospermic semen samples. An increased percentage (>30%) of spermatozoa with noncondensed ("immature") chromatin was revealed in 2 of 6 nonazoospermic semen samples analyzed by TEM., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Wire arc additive manufacturing (AM) is able to replace the traditional manufacturing processes of Ti alloys. At the same time, the common drawback of Ti workpieces produced by AM via wire deposition welding is the formation of a coarse-grained dendritic structure, its strong anisotropy and, consequently, lower strength as compared to a monolithic alloy. In this work, a new method is proposed for the enhancement of the strength properties of the Ti-6Al-4V alloy synthesized by AM via wire deposition welding, which involves the use of a wire with an initial ultrafine-grained (UFG) structure. The UFG wire is characterized by a large number of defects of the crystalline lattice and grain boundaries, which will enable increasing the number of "crystallization centers" of the α-phase, leading to its refinement. The macro- and microstructure, phase composition and microhardness of the Ti-6Al-4V alloy samples were investigated. The microhardness of the alloy produced by layer-by-layer deposition welding using a UFG wire was shown to be on average 20% higher than that of the samples produced by a deposition welding using a conventional wire. The nature of this phenomenon is discussed, as well as the prospects of increasing the mechanical characteristics of Ti alloys produced by additive manufacturing.

The authors present a patient with petroclival meningioma complicated by trigeminal neuralgia. Resection of tumor via anterior transpetrosal approach with microvascular decompression of the trigeminal nerve was performed. A 48-year-old female patient presented with left-sided (V1-V2) trigeminal neuralgia. Magnetic resonance imaging revealed a tumor 33´27´25 mm with a base adjacent to the top of petrous part of the left temporal bone, tentorium cerebelli and clivus. Intraoperative examination revealed true petroclival meningioma extending to trigeminal notch of petrous part of temporal bone. There was additional compression of trigeminal nerve by caudal branch of superior cerebellar artery. Total resection of tumor was followed by disappearance of vascular compression of trigeminal nerve and regression of trigeminal neuralgia. Anterior transpetrosal approach provides early devascularization and resection of true petroclival meningioma, as well as wide imaging of anterolateral surface of the brainstem, identification of neurovascular conflict and vascular decompression.

At present, researchers pay great attention to the development of metastable β-titanium alloys. A task of current importance is the enhancement of their strength and fatigue properties. An efficient method for increasing the strength of such alloys could be severe plastic deformation. The object of this study was a medical metastable β-titanium alloy Ti-15Mo (ASTM F2066). The alloy in the (α + β) state was for the first time deformed by combined processing, including equal channel angular pressing-conform and drawing. Such processing enabled the production of long-length rods with a length of 1500 mm. The aim of the work was to study the effect of the combined processing on the alloy's microstructure and mechanical properties. An ultrafine-grained structure with an average size of structural elements less than 100 nm was obtained. At the same time, high strength and ductility (σ uts = 1590 MPa, δ = 10%) were achieved, which led to a record increase in the endurance limit (σ -1 = 710 MPa) under tension-compression terms.

Introduction: Nowadays, due to universal newborn hearing screening (UNHS) the number of children with mild-to-moderate hearing loss diagnosed in the first year of life has increased significantly. Aside from that, identification of the genetic cause improves the genetic counselling of the families and allows to reveal possible comorbidities which may need a special approach., Objective: To present the characteristics of the early audiologic phenotype in hearing impaired patients with biallelic mutations in the USH2A gene based on systematic analysis of the audiological data., Patients and Methods: 13 patients with mutations in the USH2A gene underwent audiological examination. Most of them were found among a large group of infants with bilateral nonsyndromic sensorineural hearing loss (SNHL) examined under 12 months., Results: Eight out of eleven children failed UNHS and were initially diagnosed as having bilateral nonsyndromic SNHL. Seven children underwent an audiological assessment before the age of 9 months. The earliest audiological examination was carried out at 1 and 3 months. The children with pathogenic variants in the USH2A gene in our examined group were identified in the first year of life via UNHS. The hearing threshold levels (HTL) for the USH2A group are compactly distributed between 51.25 dB and 66.25 dB, quartiles are 54 dB and 63.4 dB, with a median of 60 dB. The audiological profile of patients with biallelic USH2A mutations differs from audiograms of patients who had STRC-related hearing loss. We have not found any significant elevation in hearing thresholds in the first decade of life. We also estimated the prevalence of the USH2A and STRC mutations among GJB2-negative infants with bilateral nonsyndromic SNHL examined under 12 months, and it was 7.5% and 16.1%, respectively., Conclusion: According to our results, the early hearing phenotype in pediatric patients with biallelic mutations in the USH2A- gene is characterized by nonsyndromic mild-to-moderate SNHL in the first decade of life. Our results indicate that the presence of mutations in the USH2A or STRC genes can be expected in a child with congenital mild-to-moderate nonsyndromic SNHL. This information is of practical importance for parents, as they have to know the prognosis of hearing loss for their child from the very beginning. Post-screening follow-up should include adequate clinical, genetic, and social support for children and their parents., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nephropathic cystinosis is a rare autosomal recessive disorder characterized by amino acid cystine accumulation and caused by biallelic mutations in the CTNS gene. The analysis methods are as follows: tandem mass spectrometry to determine the cystine concentration in polymorphonuclear blood leukocytes, Sanger sequencing for the entire coding sequence and flanking intron regions of the CTNS gene, multiplex PCR to detect a common mutation-a 57 kb deletion, and multiplex ligation-dependent probe amplification to analyze the number of exon copies in the CTNS gene. Haplotype analysis of chromosomes with major mutations was carried out using microsatellite markers D17S831, D17S1798, D17S829, D17S1828, and D17S1876. In this study, we provide clinical, biochemical, and molecular genetic characteristics of 40 Russian patients with mutations in the CTNS gene, among whom 30 patients were selected from a high-risk group of 85 people as a result of selective screening, which was carried out through cystine concentration measurement in polymorphonuclear blood leukocytes. The most common pathogenic variant, as in most described studies to date, was the 57 kb deletion, which represented 25% of all affected alleles. Previously non-described variants represented 22.5% of alleles. The founder effect in the Karachay and Chechen ethnic groups was shown for the following major variants: c.1015G > A and c.518A > G., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Savostyanov, Pushkov, Shchagina, Maltseva, Suleymanov, Zhanin, Mazanova, Fisenko, Mishakova, Polyakov, Balanovska, Zinchenko and Tsygin.)

Objectives: The present study investigated the stability of furosemide under space-flight conditions on board the International Space Station, as well as its pharmacokinetics and pharmacodynamics under conditions simulating exposure to some space-flight factors., Methods: Quantitative analysis of furosemide tablets by HPLC was performed before spaceflight (background), then after six months storage under normal ground conditions (control) and under spaceflight conditions (SF). The pharmacokinetics and pharmacodynamics of furosemide were studied in six healthy volunteers after a single oral dose of 40 mg under normal conditions (background) and under anti-orthostatic hypokinesia (ANOH)., Results: Quantitative content of furosemide in tablets before SF was 40.19 ± 0.28 mg (100.47 ± 0.71%), after 6 months storage: under normal conditions (control) - 39.9 ± 0.39 mg (99.73 ± 0.98%), under SF - 39.24 ± 0.72 mg (98.11 ± 1.80%), which was within the prescribed limits. Studying basic hemodynamic parameters showed that in ANOH conditions 6 h after furosemide administration there was a statistically significant increase of the stroke volume (SV) (+36.5 Δ%), a tendency for increasing of the stroke index (SI) (+36.5 Δ%) and decreasing of the total peripheral resistance (TPR) (-21.9 Δ%) compared to baseline study., Conclusions: It has been established that various factors of space flight (overloading, excessive vibration, microgravity, etc.) do not negatively influence the stability of furosemide in tablet form during storage for 6 months on board the International Space Station., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Gyrate chorioretinal atrophy (GCA) is a rare hereditary disease with certain complications; one extremely rare complication of GCA is foveoschisis. For the first time in Russian ophthalmology, a 10-year-old female child has been described to have genetically verified GCA associated with the OAT gene in combination with ornithinemia and foveoschisis. The diagnosis was made on the basis of fundus examination, perimetry data, autofluorescence, optical coherence tomography, fluorescence angiography, electroretinography, mass spectrometry with confirmation by molecular genetic research. The presented clinical case illustrates the need for an interdisciplinary approach to the diagnosis of GCA with diagnostic algorithm involving various examination methods and doctors of different specialties.

Objective: To present a patient with brainstem abscess treated by microsurgical resection., Case Presentation: A 53-years-old female patient admitted to the neurosurgical department in a severe condition with symptoms of intracranial hypertension, hyperthermia, general infectious signs and laboratory manifestations of infectious process. Contrast-enhanced MRI revealed a large brainstem lesion (abscess). Retrosigmoid craniotomy with total microsurgical resection of the abscess was performed. External ventricular drainage was incerted on the second postoperative day due to progressive hydrocephalus with clinical deterioration, it was removed in 8 days. Slow positive dynamics was observed in postoperative period. The patient was discharged in 2 weeks after surgery., Conclusion: There are no established algorithm for the treatment of brainstem abscesses. Therapeutic approach is advisable for small abscesses. There are 2 neurosurgical options for this lesion: stereotactic drainage and microsurgical resection with or without external ventricular drainage. Treatment strategy depends on location and size of abscess, as well as clinical state of the patient.

Objectives: To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions., Methods: The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied., Results: The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in V z for verapamil (-54 Δ%), furosemide (-20 Δ%), propranolol (-8 Δ%), and acetaminophen (-9 Δ%), but a statistically significant increase in V z was found for etacizine (+39 Δ%); there was an increasing trend in Cl t for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Cl t for etacizine, verapamil, and furosemide (-22, -23 and -9 Δ% respectively) in ANOH. The relative bioavailability of etacizine, verapamil, and furosemide in ANOH increased compared to background (+40, +23 and +13 Δ%, respectively), propranolol and acetaminophen decreased (-5 and -12 Δ% accordingly). The relative rate of absorption of etacizine and furosemide in ANOH decreased (-19 and -20 Δ%, respectively) while that of verapamil, propranolol, and acetaminophen increased (+42, +58 and +26 Δ%, respectively). A statistically significant decrease in AUC 0-∞ (-57 Δ%), C max (-53 Δ%), relative bioavailability of acetaminophen (-52 Δ%) and a sharp increase in Cl t (+147 Δ%), T max (+131 Δ%) as well as a trend towards a significant decrease in T 1/2 (-53 Δ%), MRT (-36 Δ%) and a moderate increase in V z (+24 Δ%) were found under control compared to background. Unidirectional changes in AUC 0-∞ , Cl t , T 1/2 , MRT and relative bioavailability of acetaminophen, which are more pronounced in SF and opposite dynamics for C max , T max , V z were found in ANOH and SP compared to background studies., Conclusions: The data obtained allow recommending the studied drugs for rational pharmacotherapy in the possible development of cardiovascular disease in manned spaceflight., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)