Design, Evaluation, and Determination of Antitumor Activity of Potential Inhibitors Against Protein Kinases: Application to BCR-ABL Tyrosine Kinase.

Despite significant progress made over the past two decades in the treatment of chronic myeloid leukemia (CML), there is still an unmet need for effective and safe agents to treat patients with resistance and intolerance to the drugs used in clinic. In this work, we designed 2-arylaminopyrimidine amides of isoxazole-3-carboxylic acid, assessed their inhibitory potential against Bcr-Abl tyrosine kinase, and determined their antitumor activity in K562 (CML), HL-60 (acute promyelocytic leukemia), and HeLa (cervical cancer) cells. Based on the analysis of computational and experimental data, three compounds with the antitumor activity against K562 and HL-60 cells were identified.

Conjugation with the Carrier Helped to Reveal acidification-Induced Structural Shift in the Peptide from Phospholipase Domain of Parvovirus B19.

Spectroscopic studies on domains and peptides of large proteins are complicated because of the tendency of short peptides to form oligomers in aquatic buffers, but conjugation of a peptide with a carrier protein may be helpful. In this study we approved that a fragment of SK30 peptide from phospholipase A2 domain of VP1 Parvovirus B19 capsid protein (residues: 144-159; 164; 171-183; sequence: SAVDSAARIHDFRYSQLAKLGINPYTHWTVADEELLKNIK) turns from random coil to alpha helix in the acidic medium only in case if it had been conjugated with BSA (through additional N-terminal Cys residue, turning it into CSK31 peptide, and SMCC linker) according to CD-spectroscopy results. In contrast, unconjugated SK30 peptide does not undergo such shift because it forms stable oligomers connected by intermolecular antiparallel beta sheet, according to IR-spectroscopy, CD-spectroscopy, blue native gel electrophoresis and centrifugal ultrafiltration, as, probably, the whole isolated phospholipase domain of VP1 protein does.

An Autoclavable and Transparent Thermal Cutter for Reliably Sealing Wet Nanofibrous Membranes.

Sealing wet porous membranes is a major challenge when fabricating cell encapsulation devices. Herein, we report the development of an utoclavable ransparent hermal utter (ATTC) for reliably sealing wet nanofibrous membranes. Notably, the ATTC is autoclavable and transparent, thus enabling in situ visualization of the sealing process in a sterile environment and ensuring an appropriate seal.

Implantation and removal of central temporary paracorporeal biventricular support for COVID-19-associated myocarditis.

This case report illustrates how to implant a central paracorporeal temporary biventricular assist device in a 17-year-old patient with acute heart failure due to a fulminant form of coronavirus disease 2019 myocarditis. The procedure was carried out after prior veno-arterial extracorporeal membrane oxygenation support. Myocardial biopsies and biventricular assist device explants are also included in the report.

Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe.

COVID-19 ASSOCIATED REACTIVATION OF HERPES INFECTION WITH THE DEVELOPMENT OF ENCEPHALITIS: A CASE REPORT.

The etiology of meningoencephalitis with COVID19 is coronavirus and herpetic. Secondary herpes infection is associated with immunological dysregulation or with the use of tocilizumab. Differential diagnosis of the etiology of encephalitis is important, because acyclovir is effective for herpes infection.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Unlabelled: Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions.

Purpose: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs).

Extended total colonic aganglionosis and total intestinal aganglionosis: Challenging enemies.

Aim: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms.

Flexible bronchoscopy for foreign body aspiration in children: A single-centre experience.

Background: The technological evolution of bronchoscopy has led to the widespread adoption of flexible techniques and their use for both diagnostic and therapeutic purposes. Currently, there is an active debate regarding the comparative efficacy and safety of rigid flexible bronchoscopy in the treatment of foreign body aspiration.

Aim: To evaluate our experience with tracheobronchial foreign body extraction using flexible bronchoscopy and provide a literature overview.

Balloon dilation of congenital perforated duodenal web in newborns: Evaluation of short and long-term results.

Background: Incomplete congenital duodenal obstruction (ICDO) is caused by a congenitally perforated duodenal web (CPDW). Currently, only six cases of balloon dilatation of the PDW in newborns have been described.

Aim: To present our experience of balloon dilatation of a perforated duodenal membrane in newborns with ICDO.

[Relationships between Cxcl12, Tweak, Notch1, and Yap mRNA Expression Levels in Molecular Mechanisms of Liver Fibrogenesis].

Current data on the molecular mechanisms of liver fibrosis and cirrhosis fail to fully explain all stages of their development. Interactions between individual genes and signaling pathways are known to play an important role in their functions. However, data on their relationships are insufficient and often contradictory.

Scyllatoxin-based peptide design for E. coli expression and HIV gp120 binding.

Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the host cell's CD4. Previous inhibitors, including small molecules and CD4 mimetic peptides based on scyllatoxin, have demonstrated significant binding and neutralization capabilities but were often chemically synthesized or contained non-canonical amino acids. Microbial expression using natural amino acids offers advantages such as cost-effectiveness, scalability, and efficient production of fusion proteins.

The sense of security of Ukrainians and Belarusians studying in Poland.

Introduction And Objective: Due to educational migration to Poland, students from Ukraine and Belarus may experience security to varying degrees. The aim of the study was to check the extent to which people from Ukraine and Belarus studying in Lublin feel safe, taking into account their own life and health. An attempt was also made to establish the relationship between the sense of security and selected features of the surveyed students.

A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation.

The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants.

Co-Infection of Tobacco Rattle and Cycas Necrotic Stunt Viruses in : Detection Strategies, Potential Origins of Infection, and Implications for Germplasm Conservation.

Increasing reports of tobacco rattle virus (TRV) and cycas necrotic stunt virus (CNSV) in herbaceous worldwide highlight the importance of conserving the genetic resources of this economically important ornamental and medicinal crop. The unknown origin(s) of infection, differential susceptibility of peony cultivars to these viruses, and elusive disease phenotypes for CNSV in peonies make early detection and management challenging. Here, we report the presence of TRV and CNSV in plants of the University of Michigan living peony collection in the United States and a molecular characterization of their strains.

Green-Synthesized Characterization, Antioxidant and Antibacterial Applications of CtAC/MNPs-Ag Nanocomposites.

The emergence of antibiotic resistance, caused by the improper use of antibiotics, is a significant challenge in combating infectious diseases, leading to millions of annual fatalities. The occurrence of antimicrobial side effects catalyzes the investigation of novel antimicrobial compounds and sources of drugs. Consequently, the research on biological activity that is conducted on plants, plant extracts, and compounds that are produced from plant components is of utmost significance.

Fundamentals of wildlife dosimetry and lessons learned from a decade of measuring external dose rates in the field.

Methods for determining the radiation dose received by exposed biota require major improvements to reduce uncertainties and increase precision. We share our experiences in attempting to quantify external dose rates to free-ranging wildlife using GPS-coupled dosimetry methods. The manuscript is a primer on fundamental concepts in wildlife dosimetry in which the complexities of quantifying dose rates are highlighted, and lessons learned are presented based on research with wild boar and snakes at Fukushima, wolves at Chornobyl, and reindeer in Norway.

The European psychiatric association (EPA) - early career psychiatrists committee survey on trainees' and early-career psychiatrists' attitudes towards therapeutic drug monitoring (TDM) use and utility during antipsychotic treatment.

Objectives: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics.

Methods: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis.

Exploring the accessibility of primary health care data in Europe's COVID-19 response: developing key indicators for managing future pandemics (Eurodata study).

Background: Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC's clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC's role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics.

Assessment of Various Nanoprimings for Boosting Pea Germination and Early Growth in Both Optimal and Drought-Stressed Environments.

One of the main climate change-related variables limiting agricultural productivity that ultimately leads to food insecurity appears to be drought. With the use of a recently discovered nanopriming technology, seeds can endure various abiotic challenges. To improve seed quality and initial growth of 8-day-old field pea seedlings (cv.

Global biochemical profiling of fast-growing Antarctic bacteria isolated from meltwater ponds by high-throughput FTIR spectroscopy.

Fourier transform infrared (FTIR) spectroscopy is a biophysical technique used for non-destructive biochemical profiling of biological samples. It can provide comprehensive information about the total cellular biochemical profile of microbial cells. In this study, FTIR spectroscopy was used to perform biochemical characterization of twenty-nine bacterial strains isolated from the Antarctic meltwater ponds.

Effectiveness and safety of modified fully oral 9-month treatment regimens for rifampicin-resistant tuberculosis: a prospective cohort study.

Background: In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide, ethambutol, high-dose isoniazid, pyrazinamide, and clofazimine for the management of rifampicin-resistant tuberculosis. A high prevalence of resistance to constituent drugs precluded its widespread use by countries in the WHO European region. We evaluated three 9-month fully oral modified STRs (mSTRs) in which ethionamide, ethambutol, isoniazid, and pyrazinamide were replaced by linezolid, cycloserine, or delamanid (or a combination).