Abstract

Social avoidance in the concept of “avoidance of corrective  emotional experience” is regarded as one of the pathogenetic  factors that aff ect the course and development of mental disorders and increase distress. We conducted a review of studies that studied the role of social avoidance in social anxiety disorder among individuals with or without post-traumatic experience. Inclusion criteria were: 1) subjects were diagnosed with social anxiety disorder; 2) social anxiety disorder and/or post-traumatic stress was a focus of the study; 3) some assessment or review impact of social avoidance was made; 4) subjects were adolescents or adults. The study of the role of avoiding social events as a traumatic trigger and related socially significant factors (stigma, discrimination, living at constant risk, etc.) indicates a correlation between the pathogenesis of social phobia and comorbid symptoms of post-traumatic distress. Managing social avoidance strategies and accepting the conscious experience of social interaction presupposes a person’s readiness to reactflexibly, stay in contact with their emotions and thoughts, and not spend internal resources to get rid of the inner concerns. In our opinion, this will help reduce the perception of social events as a traumatic (retraumatic) factor, reduce clinically significant manifestations of social anxiety and prevent the development of post-traumatic distress. Limitations and implications of these fi ndings for the psychological support and modifying psychotherapeutic interventions of social anxiety disorder are discussed.

ABSTRACT

The aim: To examine the features of experiences of bereavement reactions and the severity of comorbid mental health problems in persons who lost loved ones during the pandemic.

Materials and methods: 191 volunteers aged 18-60 years participated in this study. All participants were tested during 2018-2020. To assess the mental health problems was used International Neuropsychiatric Interview (MINI) and a set of IAPT scales; to the psycho-emotional distress severity associated with loss of loved ones – Inventory of Complicated Grief, with verification of symptoms of complicated grief based on an independent assessment of two experts; and the quality of life satisfaction was assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form.

Results: The results show an association between the severity of symptoms of depression, general anxiety, social avoidance, and loss during the pandemic. The level of psychoemotional distress was associated with the experience of bereavement as a traumatic event for a group of participants who experienced loss during the pandemic and, at the same time, before the pandemic was associated with the severity of depression. Regardless of the time of loss, people who demonstrated signs of complicated grief have a more pronounced comorbid psychopathology, a higher level of psycho-emotional distress, and a lower level of satisfaction with life quality.

Conclusions: It has been established that a person’s ability to experience loss as a traumatic experience and grieve during the pandemic is modified with the context of the life situation and reflects those challenges that impose quarantine restrictions

ABSTRACT The aim: To study the structure of cognitive impairment in patients who were hospitalized with moderate to severe COVID-19 pneumonia. Investigate the correlation with demographic, biochemical parameters, as well as the emotional state of the patient. Materials and methods: Cognitive functions were assessed using the MOCA test.PHQ-9 depression and GAD-7 anxiety questionnaires were used to study psychopathological symptoms. Demographic, clinical and laboratory data were extracted from medical records Results: Cognitive performance is impaired in 94% of patients with COVID-19. This allows to suggest that COVID-19 has a serious impact on cognition, especially in elder people. Among different domains only visuospatial and executive functioning, abstract thinking, attention and delayed recall were severely impaired, while other domains stayed relatively intact. Patients after COVID-19 also tend to have a mild depressive and anxiety state. Anxiety levels were higher than depressive levels, but not connected to cognitive functioning. Also, there was seen a positive correlation between anxiety and pO2 and negative between anxiety and comorbid cardiac pathology. However, this requires further studies to reveal. Another interesting finding was non-linear relationship between cognitive performance and depression, that allows to suggest rapidly evolving depressive mood in persons with severe cognitive impairment after COVID-19. Cognitive and emotional state of patients after COVID-19 was also highly connected with working status. Conclusion: Significant cognitive impairment was presented in almost all patients with COVID-19. There was a selective impairment in domains of visuospatial/ executive functioning, abstract thinking, attention and delayed recall.

Pericardial effusion (PE) can occur in inflammatory and infectious diseases; postoperatively, in pulmonary arterial hypertension, renal failure, as well as in malignant diseases that can affect the pericardium and manifest as a paraneoplastic syndrome (1). On the other hand, the presence of blood in the pericardial cavity – hemopericardium – is more commonly seen in aortic dissection, cardiac rupture, trauma, or after invasive procedures (2) and less frequently in malignant cardiac tumors. The late diagnosis of content in the pericardial cavity, often due to the absence of specific symptoms, can lead to delayed detection and preclude radical treatment in the case of tumors or neoplastic heart lesions. However, early diagnosis and tumor resection can significantly improve patients' condition and allow for life-extending chemotherapy (3). This case highlights the critical importance of early detection in pericardial effusion. The purpose of presenting this clinical case is to increase awareness and alertness among family doctors, therapists, cardiologists, cardiothoracic surgeons, and radiologists to exclude neoplastic involvement of the heart when hydro- or hemopericardium is detected.

Computer-aided rational drug design encompasses the identification of potential biological targets for drug candidates followed by an intensive search ensues to find a drug-like small molecules that can modulate the function of the identified macromolecule resulting in a therapeutic effect. This approach becomes possible due to the availability of information about the three-dimensional chemical structures of ligands and biomolecules. Thus, to be efficient, computer-aided drug design (CADD) techniques including both ligand- and structure-based, must be accurate with the structural data manipulation as the knowledge of macromolecules and ligands structures as well as unbound and receptor-bound conformations is the precondition of the vital importance for the application of 3D computational molecular modeling approaches.

The aim of the current work was to analyze, systematize and summarize the recent literature data discussing conformational ensembles of small organic molecules, the main approaches and techniques applied for their generation and the conformational sampling of drug-like molecules significance in modern computer-aided drug design. 

 Three-dimensional spatial arrangements of atoms that organic molecules can adopt are known as conformations, their diversity is ensured by rotational bonds, changes in bond lengths, bond angles and torsions, interconversion between different conformations can be achieved by rotations about formally single bonds. Thus, a set of stable spatial geometric structures of a molecule with the constant connectivity matrix constitutes the set of its conformations. In their turn, conformational ensembles are represented by the sets of equilibrium conformations existing under certain thermodynamic conditions in defined environmental medium. Consequently, thorough conformational analysis is critically important in many areas of research, such as drug discovery, protein engineering, and the design of catalysts.

Conformer generation leading to exploring and sampling the low energy conformational space of drug-like molecules continues to be a relevant task focusing on ligands structure pre-organization with the aim to minimize energetic penalties associated with undesired flexibility, sub-optimal arrangement of functional groups interacting with the protein binding site or unwanted internal stabilization.

Drug-like molecules can adopt a great number of conformations depending on the amount of rotatable bonds, angels and torsions flexibility and the rigidity properties of their rings and cycles. It was shown that even the solid-state ligands bounded to corresponding biotargets can possess conformational diversity. Structural data drawn from the Protein Data Bank (PDB) revealed that the same ligand precented in at least two different protein−ligand structures may be found in multiple conformations which differed significantly (RMSD > 2 Å) [1]. This means that a small molecule must adopt the bioactive conformation that is the conformation which can be recognized by the receptor and produce the biological response. Bioactive conformations construction for flexible small organic molecules is challenging and complex problem in modern drug design reasoned by the large number of degrees of freedom even for relatively small ligands.