The Ukrainian refugee crisis: its ethical aspects and the challenges for the Polish healthcare system – a descriptive review

Since the start of the Russian Invasion of Ukraine on 24.02.2022, millions of people (mostly women and children) have fled Ukraine. Majority of them fled to Poland and providing adequate medical care for the massive influx of refugees is a considerable challenge for the Polish healthcare system, already burdened by the COVID-19 pandemic and staff shortages. The purpose of this study was to identify: the potential health problems of the incoming population, the legal and ethical aspects of the refugee crisis and its implications on public health. Combining the current data with previous research on refugee crises reveals a set of issues that need to be addressed. Ensuring continuity of chronic disease treatment, mental health, the risk of spreading vaccinable preventable diseases, high rates of tuberculosis, HIV and the ongoing COVID-19 pandemic are among the main concerns. In the near future, answers will have to be found to the emerging ethical questions of equal, safe access to care, implications of the language barrier, immunisation coverage, medical staff shortages, and existing legal and ethical regulations. As the emergency responses are addressed, the hosting countries need to prepare long-term resolutions

Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin

Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of amyloid fibrils formed by the association of ACC1-13 aggregation-prone peptides derived from the N-terminal region of insulin’s A-chain. First, a large number of protofilament models composed of five copies of interacting ACC1-13 peptides were predicted by application of CABS-dock coarse-grained (CG) docking simulations. Next, the models were reconstructed to all-atom (AA) representations and refined during molecular dynamics (MD) simulations in explicit solvent. The top-scored protofilament models, selected using symmetry criteria, were used for the assembly of long fibril structures. Finally, the amyloid fibril models resulting from the AA MD simulations were compared with atomic force microscopy (AFM) imaging experimental data. The obtained results indicate that the proposed multi-scale modeling procedure is capable of predicting protofilaments with high accuracy and may be applied for structure prediction and analysis of other amyloid fibrils

Molecular Dynamics Scoring of Protein–Peptide Models Derived from Coarse-Grained Docking

One of the major challenges in the computational prediction of protein–peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein–peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor–ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein–peptide complexes show that the proposed MD-based scoring approach can be used to identify protein–peptide models of high accuracy. The results also indicate that the scoring accuracy may be significantly affected by the quality of the reconstructed protein receptor structures

The Ukrainian refugee crisis: its ethical aspects and the challenges for the Polish healthcare system – a descriptive review

Since the start of the Russian Invasion of Ukraine on 24.02.2022, millions of people (mostly women and children) have fled Ukraine. Majority of them fled to Poland and providing adequate medical care for the massive influx of refugees is a considerable challenge for the Polish healthcare system, already burdened by the COVID-19 pandemic and staf shortages. The purpose of this study was to identify: the potential health problems of the incoming population, the legal and ethical aspects of the refugee crisis and its implications on public health. Combining the current data with previous research on refugee crises reveals a set of issues that need to be addressed. Ensuring continuity of chronic disease treatment, mental health, the risk of spreading vaccinable preventable diseases, high rates of tuberculosis, HIV and the ongoing COVID-19 pandemic are among the main concerns. In the near future, answers will have to be found to the emerging ethical questions of equal, safe access to care, implications of the language barrier, immunisation coverage, medical staf shortages, and existing legal and ethical regulations. As the emergency responses are addressed, the hosting countries need to prepare long-term resolutions. Kolińska K, Paprocka-Lipińska A, Koliński M. The Ukrainian refugee crisis: its ethical aspects and challenges for the Polish healthcare system - a descriptive review. Eur J Transl Clin Med. 2023;6(1):79-86

Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of <i>Staphylococcus aureus</i> DNA Topoisomerase IV and Gyrase

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1–3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1, 2, 3 were within the range of 0.8–3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1–3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates

Menthol- and thymol-based ciprofloxacin derivatives against Mycobacterium tuberculosis: in vitro activity, lipophilicity, and computational studies

Abstract In this work, we investigated the antitubercular properties of Ciprofloxacin derivatives conjugated with menthol and thymol moieties. For the sixteen derivatives, we established minimal inhibitory concentrations (MIC) using isolates of Mycobacterium tuberculosis that were resistant or susceptible to other antibiotics. For the most potent compound 1‐cyclopropyl‐6‐fluoro‐7‐{4‐[6‐((1R,2S,5R)‐2‐isopropyl‐5‐methylcyclohexyloxy)‐6‐oxohexyl]piperazin‐1‐yl}‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic acid (6), we determined fractional inhibitory concentration index (FICI) values to confirm antibacterial susceptibility and synergistic effects with other reference drugs. In addition, chromatographic studies of all the derivatives demonstrated a significant three to four-fold increase in lipophilicity and affinity to phospholipids compared to Ciprofloxacin. Finally, we conducted structure-based studies of the investigated compounds using molecular docking and taking into account protein target mutations associated with fluoroquinolone resistance. In summary, our findings indicate that the investigated compounds possess tuberculostatic properties, with some showing similar or even better activity against resistant strains compared to reference drugs. Increased lipophilicity and affinity to phospholipids of the new derivatives can offer several advantages for new drug candidates, beyond just improved cell membrane penetration. However, further studies are needed to fully understand their safety, efficacy, and mechanism of action