Implantation of a hemodialysis catheter directly in the right atrium due to exhaustion of vascular access

Introduction: Patients on permanent hemodialysis need constant and secure vascular access with optimal flow to perform the procedure. Failure to provide such access can lead to life-threatening deterioration of the patient's condition.Case Presentation: We report a case of implantation of a hemodialysis catheter directly in the right atrium (RA) in an emergency in a 46 year-old woman, placed on permanent hemodialysis (HD) for nine years due to end-stage renal disease with exhausted opportunities for vascular access over the years and unsuitable for peritoneal dialysis.After a consultation between a cardiac surgeon, a vascular surgeon and an interventional radiologist, a decision was made to directly implant a permanent catheter for HD in the superior vena cava (SVC).The operation was performed as a matter of urgency, operative access was through ministerotomy and the catheter was implanted directly in the right atrium (RA) due to thrombosis and fibrosis of the SVC. No cardiac complications associated with the procedure were observed in the postoperative period. On the first postoperative day, HD was performed, followed by others according to the therapeutic plan. The patient was discharged from the Cardiac Surgery Department on the 7th postoperative day.Conclusion: The use of open surgical access and the implantation of a permanent HD catheter directly into the RA can be considered a life-saving procedure in HD patients with acute uremic syndrome and exhausted vascular access

EVALUATION OF THE ESTROGENIC EFFECT OF POLYCHLORINATED BIPHENYLS WITH REGARD TO THEIR METABOLIC ACTIVATION BY APPLICATION OF IN SILICO TECHNOLOGIES

Hydroxylated polychlorinated biphenyls (OH-PCBs) major metabolites of PCBs, have been reported to present affinity to the estrogen receptor and induce receptor-mediated responses. The early identification of PCBs which may act as estrogen binders was investigated by making use of computational tools for chemical risk assessment. As an area of growing concern a strategy for development of such tools is one of the primary tasks of governmental and international organizations. In the current study the estrogenic potential of several PCBs is analyzed by using widely accepted and standardized computational program. The obtained results suggest that the system is equipped with scientific reliable modules for prediction of the estrogenic potential of diverse chemicals as well as robust machinery for adequate metabolism simulation

PREDICTION OF HEPATOCARCINOGENIC EFFECT OF STRUCTURAL DIVERSE CHEMICALS BY COMPUTATIONAL TECHNOLOGIES

The primary testing strategy to identify chemical (hepato)carcinogens largely relies on the 2-year rodent bioassay, which is time-consuming and labor-intensive. There is an increasing effort to develop alternative approaches to prioritize the chemicals for, supplement, or even replace the cancer bioassay. In silico approaches based on quantitative structure-activity relationships (QSAR) are rapid and inexpensive and thus have been investigated for such purposes. Since the correlation between carcinogenicity and Ames mutagenicty test results was found to be significant enough it is expected that models based on Ames data could be used successfully for identification of chemical carcinogens. In the current study the implemented profiler for DNA binding prediction in non-commercial software tool was used to predict the hepatocarcinogenic effect of 55 representative chemicals. The obtained results show that 73% of the hepatocarcinogens can be successfully identified as genotoxic carcinogens. The role of nongentoxic mechanisms has been assessed by application of profiling scheme for identification of nongenotoxic chemical carcinogens. As a result of combined application of both profilers 87% of hepatocarcinogens have been correctly identified

IN SILICO IDENTIFICATION OF HUMAN PREGNANE X RECEPTOR ACTIVATORS

The nuclear receptor member human pregnane X receptor (hPXR) regulates enzymes and transporters involved in xenobiotic detoxification as well as maintains homeostatic balance of bile acids, thyroid and steroid hormones. hPXR can be recognized and activated by a structurally diverse array of environmental chemicals and drug compounds to initiate adverse biological effects, such as perturbing normal physiological functions and causing dangerous drug–drug interactions and exhibiting a high promiscuity in its ligand spectrum. In the current study capabilities for structure-activity modeling incorporated in the platform QSAR Toolbox were employed for investigation the binding mode and structural basis of hPXR interactions with various activators and non-activators. A total of 348 molecules, representing a variety of chemical structures, constituted the training set of the model. Validation of the model showed a sensitivity of 70%, a specificity of 85%, and a concordance of 77%. The developed model provide knowledge about molecular descriptors that may influence the effect of molecules to hPXR

IDENTIFICATION OF ENDOCRINE DISRUPTING CHEMICALS BY IN SILICO METHODS

Identification of endocrine disrupting chemicals (EDCs) is one of the important goals of environmental chemical hazard screening. It is exhaustive and time consuming to test in vitro all chemicals – potential EDCs – used in industry, agriculture or as food preservatives against their effects on the endocrine system. Computational methods, such as virtual screening, quantitative structure activity relationships and docking, are already well recognized and used in many strategic programs for identification of EDCs. The aim of this study was to evaluate the predictive performances of model for identification of EDCs integrated in non-commercial software tool. The resulting statistics indicated that the binding affinities of the majority of chemicals included in the external validation dataset could be correctly predicted. However, a set of further improvements has been suggested in order to increase the predictive ability of the current profiling scheme for EDCs

Emotional intelligence of students during pandemic outbreak : a study in higher education

Emotional intelligence is a main area in educational psychology and a key factor in the academic life of students. In the current study the dimensions of emotional intelligence - self-awareness, managing emotions, motivating oneself, and social skills were examined in order to identify negatively affected aspects due to the COVID 19 outbreak. Data was gathered from students from University “Prof. Dr. Asen Zlatarov”, Burgas, Bulgaria through a self-completion electronic questionnaire which includes a total of 50 questions related to emotional intelligence. The obtained results are processed by making use of intuitionistic fuzzy set (IFS) techniques. It was found that there are is no significant influence of pandemic situation on emotional condition of the students. However, a set of elements associated to the dimensions of emotional intelligence should be taken into account in order to support the success of students during their education and further professional realization

Application of virtual reality as a tool for structural analysis of molecules : steroids, pharmaceuticals and pesticides

The three dimensional nature of chemical interactions requires application of suitable technology for visualization of molecules in order to assess their reactivity. The molecular flexibility of organic chemicals allows those structures to exist in a set of different structural orientation (conformations) as a result of changes of structural variables such as bond rotation, valence angles and many other. Each spatial position may differ significantly in respect to chemical reactivity. Thus, in order to make an overall reactivity profile of a specific chemical all possible 3D positions should be considered and analyzed. In the current paper the focus is set on representative chemicals from groups of steroids, pharmaceuticals and pesticides. In order to analyze the reactivity of those chemicals the following steps are accomplished: 1) generation of initial 3D structures; 2) generation of possible 3D structural orientation; and 3) visualization of the 3D structures in a suitable virtual reality tool for education purposes

JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors.

Rapid emergence of tumor resistance via RAS pathway reactivation has been reported from clinical studies of covalent KRASG12C inhibitors. Thus, inhibitors with broad potential for combination treatment and distinct binding modes to overcome resistance mutations may prove beneficial. JDQ443 is an investigational covalent KRASG12C inhibitor derived from structure-based drug design followed by extensive optimization of two dissimilar prototypes. JDQ443 is a stable atropisomer containing a unique 5-methylpyrazole core and a spiro-azetidine linker designed to position the electrophilic acrylamide for optimal engagement with KRASG12C C12. A substituted indazole at pyrazole position 3 results in novel interactions with the binding pocket that do not involve residue H95. JDQ443 showed PK/PD activity in vivo and dose-dependent antitumor activity in mouse xenograft models. JDQ443 is now in clinical development, with encouraging early phase data reported from an ongoing Phase Ib/II clinical trial (NCT04699188)