Experience of Parents of Children with Genetically Determined Leukoencephalopathies Regarding the Adapted Health Care Services During the COVID-19 Pandemic

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopathies during the pandemic given the adapted health care services. We conducted semistructured interviews with 13 parents of 13 affected children. Three main themes were identified using thematic analysis: perceived impact of COVID-19 on health care services, benefits and challenges of telemedicine, and expectations of health care after the pandemic. Parents perceived a loss/delay in health care services while having a positive response to telemedicine. Parents wished telemedicine would remain in their care after the pandemic. This is the first study assessing the impact of COVID-19 on health care services in this population. Our results suggest that parents experience a higher level of stress owing to the shortage of services and the children's vulnerability.

Phenotypical Comparison of Pseudomonas Aeruginosa Isolated from Human and Veterinary Samples; Impact of Host Adaptation on Infection Pathogenesis

Purpose: Determinants of virulence in Pseudomonas aeruginosa vary strongly depending on its habitat. In this study, we analyzed these alterations depending on the host organism in isolates cultured from canine ears and compared it to clinical extended-spectrum antibiotic-resistant Pseudomonas aeruginosa isolates (XDR), clinical antibiotic-sensitive (non-XDR) from humans and environmental isolates (EI) analyzed during our first study in 2017. Methods: A total of 22 veterinary isolates cultured from canine ears (VET) were examined for spontaneous biofilm formation, stress response in biofilm formation induced by meropenem, in vitro fitness, susceptibility to human serum and polymorphonuclear leukocytes and the genetically determined virulence factors toxA, exoS, exoT, exoU, exoY, nan1, cif, lasA and lasB.Results: We observed significantly elevated spontaneous biofilm formation and serum susceptibility in VET isolates compared to EI and non-XDR isolates as well as significantly decreased in vitro fitness compared to XDR isolates. The VET isolates resembled most the XDR subgroup of isolates previously cultured from blood. Within the environmental isolates, we observed an increase of spontaneous biofilm formation and exoU presence in isolates cultured from community water samples over hospital water samples to pool samples.Conclusions: Considering the distinct differences in some features of the examined VET isolates, a higher degree of phenotypical adaption can be assumed. Increased biofilm formation seems to be a common and characteristic event in isolates adapted to a specific habitat. Therefore amplification of potentially more virulent Pseudomonas aeruginosa strains in domestic animals may lead to elevated zoonotic risk for example for pet owners.

Candidate genes of the development of antipsychotic-induced parkinsonism in patients with schizophrenia

Antipsychotic-induced parkinsonism is an undesirable reaction from the extrapyramidal system that occurs against the background of taking antipsychotics (AP), more often in patients with schizophrenia. Antipsychotic-induced parkinsonism belongs to the group of secondary parkinsonism. Its prevalence in the world is about 36%. It is assumed that this undesirable AP reaction is genetically determined. In recent years, numerous associative genetic studies of predisposition to the development of antipsychotic-induced parkinsonism have been conducted. However, the research results are contradictory.Purpose. Review of the results of studies of genetic predictors of antipsychotic-induced parkinsonism in patients with schizophrenia.Materials and methods. We searched for full-text publications in Russian and English in the RSCI, PubMed, Web of Science, Springer databases using keywords and combined searches for words over the past decade.Results. The review considers candidate genes encoding proteins/enzymes involved in the pharmacodynamics and pharmacokinetics of AP. We analyzed 23 genome-wide studies examining 108 genetic variations, including SNV/polymorphisms of 26 candidate genes involved in the development of AIP in schizophrenic patients. Among such a set of obtained results, only 22 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3; VNTR*9R DAT1; rs4680 (G/A) СOMT; rs6311 (C/T) 5HTR2A; rs6318 (C/G), rs3813929 (С/Т), haplotype-997G, -759C, -697C и 68G HTR2C; rs2179652 (C/T), rs2746073 (T/A), rs4606 (C/G), rs1152746 (A/G), rs1819741 (С/Т), rs1933695 (G/A), haplotype rs1933695-G, rs2179652-C, rs4606-C, rs1819741-T и rs1152746-G, haplotype rs1933695-G, rs2179652-T, rs4606-G, rs1819741-C и rs1152746-A RGS2; haplotype TCCTC ADORA2A; rs4795390 (C/G) PPP1R1B; rs6265 (G/A) BDNF; rs12678719 (C/G) ZFPM2; rs938112 (C/A) LSMAP; rs2987902 (A/T) ABL1; HLA-B44; rs16947 (A/G), rs1135824 (A/G), rs3892097 (A/G), rs28371733 (A/G), rs5030867 (A/C), rs5030865 (A/C), rs1065852 (C/T), rs5030863 (C/G), rs5030862 (A/G), rs28371706 (C/T), rs28371725 (A/G), rs1080983 (A/G) CYP2D6. However, at the present time it should be recognized that there is no final or unique decision about the leading role of any particular SNV/polymorphism in the development of AIP.Conclusion. Disclosure of genetic predictors of AP-induced parkinsonism development may provide a key to the development of a strategy for personalized prevention and treatment of the neurological complication of AP-therapy of schizophrenia in real clinical practice.

New genetically determined risk factors of diabetic retinopathy in type 2 diabetes mellitus: final report

Background. According to the International Diabetes Federation, the number of people with diabetes mellitus is going to increase from 366 to 552 million by 2030. More than 1.5 million patients with diabetes are registered in Ukraine, of which 84–95 % have type 2 diabetes. Diabetic retinopathy (DR) is one of the common diabetes complications, being one of the leading causes of blindness and low vision, in particular in people of occupational age. Metabolic disorders, including activation of the polyol pathway of glucose utilization, play an important role in the pathogenesis of DR, with aldose reductase playing a key role, the activity of which is associated with the polymorphism of its gene, AKR1B1. The study of new meta­bolic and genetic mechanisms for the development and progression of DR in type 2 diabetes mellitus in patients from the Ukrainian population is an actual task of modern ophthalmology. Purpose: to investigate and generalize new genetically determined risk factors for diabetic retinopathy in type 2 diabetes mellitus. Materials and methods. The study involved 409 participants, who were divided into four groups: 1 — comparison cohort (98 people without diabetes mellitus type 2); 2 — 76 patients (stage I DR, without fundus chan­ges); 3 — 64 individuals with non-proliferative DR; 4 — 64 patients with proliferative DR; control group for genetic researches included 107 ophthalmologically healthy individuals. All patients underwent blood sampling for molecular genetic research by puncture of the ulnar vein and aspiration of 2.5 ml of blood through a 23G 5.0 ml disposable syringe (Hemoplast, Etalon+, Ukraine), followed by a release into a 3.0 ml container (Vacuette K3E K3EDTA, Greiner Bio-One, Austria). Distribution of polymorphic alleles and genotypes of rs759853 and rs9640883 aldose reductase gene (AKR1B1) in patients with non-proliferative DR, proliferative DR and in the control group and their association with disease and effects on the occurrence, mechanisms of development and progression of DR were studied. Based on the conducted researches, a model of DR development prognosis was developed by construction of multiple regression with sufficient reliability of degree of influence of independent variables on a calculated indicator. Results. As a result of our research, we identified new genetically determined risk factors for the development and progression of the different stages of DR in patients with diabetes mellitus type 2, namely the role of polymorphic alleles and genotypes rs759853 and rs9640883 of the AKR1B1 gene. The deve­loped logistic regression models found that the risk of DR incidence is five times lower in carriers of the G/G and G/A genotypes compared to carriers of the A/A genotype rs759853 polymorphism (p < 0.001). It was found that the risk is twice as high (p = 0.01) for carriers of the G/G genotype rs9640883 compared to the A/A + G/A genotypes. The risk of developing proliferative DR is 3.3 times lower in carriers of the G/G genotype and 2.5 times lower in carriers of the G/A genotype compared to carriers of the A/A genotype rs759853. Conclusions. Therefore, on the basis of our clinical, ophthalmological, molecular genetic and statistical studies we have identified new risk factors for the development and progression of different stages of DR in patients with diabetes mellitus type 2. Mathematical models of development and progression of different stages of DR in patients with diabetes type 2 were built.

THE ROLE OF THE CONSTITUTION IN THE FORMATION OF A HARMONIOUS PERSONALITY OF A MEDICAL STUDENT

Why does a person need to know their body type? What does it affect? It turns out, almost everything. Physique is genetically determined and cannot be altered through exercise or diet. It is this that "tells" our body how to work: in what places to accumulate fat, how to quickly gain weight and lose it. It is the features of our constitution that influence the choice of style and cuts of clothing, and even leave an imprint on the character and perception of ourselves and the world around us!

Psychopathy as a Modus of Human Destructiveness in the Literary and Philosophical Reflection of Postmodernity (Based on the Novels "A Clockwork Orange" by A. Burgess and "The Wasp Factory" by I. Banks)

The sociopolitical circumstances of people's lives are constantly changing, which is studied by science, philosophy and art. The twentieth century is a time of great upheavals that changed the approach to the concept of man and the field of his existence. Philosophers of the second half of the twentieth century pay attention to the destructive nature of state power, its institutions are interpreted as suppressing freedom and consolidating violence as an ideology (the Frankfurt School, J. Baudrillard, S. Zizek, etc.). Another important concept is the interpretation of destructive impulses as a normal component of a person (J. Bataille, Z. Freud, E. Fromm, J. Deleuze, etc.). This idea creates a pattern of behavior that is considered psychopathic in the article. Psychopathy is a genetically determined type of antisocial personality. The phenomenon of psychopathy is a subject not only of scientific study, but also of art: the psychopath became a central character in many works of literature and cinema in the second half of the twentieth century. The article analyzes the novels "A Clockwork Orange" by E. Burgess (1962) and "The Wasp Factory" by I. Banks (1984), where the main characters are teenage psychopaths. The article concludes that these works complement each other, exploring two main areas of human life (the world of the state and the world of the family). It is suggested that by referring to the psychopathic hero, writers describe the changes that take place in society, these changes are also analyzed by philosophers. The fact that psychopathic traits in novels are concentrated in the images of teenagers indicates the possibility of psychopathy developing and spreading in the future.

Adult Still's disease: New horizons

Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of “pro-inflammatory” cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented.Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1β - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.

Multiple Data Demonstrate That Bacteria Regulating Reproduction Could Be Not the Cause for the Thelytoky of Diglyphus wani (Hymenoptera: Eulophidae)

In Hymenoptera parasitoids, the reproductive mode is arrhenotoky, while a few species reproduce by thelytoky. The thelytoky of Hymenoptera parasitoids is generally genetically determined by the parasitoids themselves or induced by bacteria, including Wolbachia, Cardinium, and Rickettsia. Diglyphus wani (Hymenoptera: Eulophidae), a recently reported thelytokous species is a main parasitoid attacking agromyzid leafminers. To assess whether endosymbionts induce thelytoky in D. wani, we performed universal PCR detection and sequenced the V3-V4 region of 16S ribosomal RNA gene. In addition, bacteria were removed through high-temperature and antibiotic treatments, and the localized bacteria were detected using FISH. Based on general PCR detection, Wolbachia, Cardinium, Rickettsia, Arsenophonus, Spiroplasma, and Microsporidia were absent in laboratory and field individuals of thelytokous D. wani. Furthermore, 16S rRNA gene sequencing revealed that the dominant endosymbionts in thelytokous D. wani were not reproductive manipulators. High-temperature and antibiotic treatment for five consecutive generations cannot reverse the thelytokous pattern of D. wani, and no male offspring were produced. Moreover, no bacterial spots were found in the ovaries of D. wani. Thus, it is considered that the thelytoky of D. wani does not result in the presence of endosymbionts. This species is thus the second reported eulophid parasitoid whose thelytoky appears not to be associated with endosymbionts.

Fixed nature and dynamic processes in Hahnemann's thought

Background and Aims. At least since classical Greek philosophy two opposite vews are facing, the one of Heraclitus, affirming that all things are in a continuous flux, and the other of Parmenides, the assertor of changelessness. The aim of present contribution is to consider if and how the tension between such views continues to permeate several features of the culture, including the thought of S. Hahnemann. Methods. This will be achieved through the examination of some cases in the natural sciences and human sciences, including Hahnemann’s writings. Few examples are presented here. The living being can be viewed as a thing genetically determined, or as an open and dynamic complex of processes interacting mutually and with the environment at metabolic and informational levels. The central nervous system is seen to underlie both automatic, and creative behaviours. A species is considered a pure ideal type, or a historically varying population of similar individuals. The basic traits of human behaviour are attributed to an unchanging nature (better, a nature undergoing slow Darwinian changes), or to a culture evolving in a rapid Lamarckian way. Within an integrated view of the person one may consider both the four fixed human constitutions (see H. Bernard; M. Martiny; N. Pende; A. Negro), and their four changing constitutional stages (see H. Bernard). Classical culture highlights the paramount importance of universal principles, while postmodern culture highlights proteanism, liquid state, patchwork. In particular, we may encounter such two views in the thought of Hahnemann on diseases. They are found in his writings respectively on the chronic diseaes, and on the so-called non-miasmatic diseases. About chronic diseases, he wrote that they are primitive, deeply-rooted, underlying external symptoms, old, universal, always recurring, internal, and do not desappear even when external symptoms of acute diseases desappeared, while the whole symptoms of them must be extensivery taken into account. About non-miasmatic diseases, he wrote that the complex of symptoms of a single case, which is always different for each individual case, cannot be foreseen, nor schematized, nor taken as a model, nor treated by an a priori chosen remedy or with a priori rules different from the strict application of the so-called law of similars, experimentally established. Conclusions. We may conclude that Hahnemann’s integrated consideration of diseases takes into account both the fixed characteristics of the chronic ones and the dynamic processes of the acute ones, so that the two above views appear to be not opposed, but perfectly integrated.