Development and validation of LC-MS/MS methods for the pharmacokinetic assessment of the PROTACs bavdeglutamide (ARV-110) and vepdegestrant (ARV-471).

Chemically induced, targeted protein degradation with proteolysis targeting chimeras (PROTACs) has shown to be a promising pharmacological strategy to circumvent the poor "druggability" of intracellular targets. However, the favorable pharmacology comes with complex molecular properties limiting the oral bioavailability of these drugs. To foster the translation of PROTACs into the clinics it is of high importance to establish sensitive bioanalytical methods that enable the assessment of absorption, bioavailability, and disposition of PROTACs after oral dosing.

Grazing-incidence synchrotron radiation diffraction studies on irradiated Ce-doped and pristine Y-stabilized ZrO at the Rossendorf beamline.

In this work, Ce-doped yttria-stabilized zirconia (YSZ) and pure YSZ phases were subjected to irradiation with 14 MeV Au ions. Irradiation studies were performed to simulate long-term structural and microstructural damage due to self-irradiation in YSZ phases hosting alpha-active radioactive species. It was found that both the Ce-doped YSZ and the YSZ phases had a reasonable tolerance to irradiation at high ion fluences and the bulk crystallinity was well preserved.

Challenges in Permeability Assessment for Oral Drug Product Development.

Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development.

GSK3α Regulates Temporally Dynamic Changes in Ribosomal Proteins upon Amino Acid Starvation in Cancer Cells.

Amino acid availability is crucial for cancer cells' survivability. Leukemia and colorectal cancer cells have been shown to resist asparagine depletion by utilizing GSK3-dependent proteasomal degradation, termed the Wnt-dependent stabilization of proteins (Wnt/STOP), to replenish their amino acid pool. The inhibition of GSK3α halts the sourcing of amino acids, which subsequently leads to cancer cell vulnerability toward asparaginase therapy.

Surface Multifunctionalization of Inert Ceramic Implants by Calcium Phosphate Biomimetic Coating Doped with Nanoparticles Encapsulating Antibiotics.

Aseptic loosening and periprosthetic infections are complications that can occur at the interface between inert ceramic implants and natural body tissues. Therefore, the need for novel materials with antibacterial properties to prevent implant-related infection is evident. This study proposes multifunctionalizing the inert ceramic implant surface by biomimetic calcium phosphate (CaP) coating decorated with antibiotic-loaded nanoparticles for bioactivity enhancement and antibacterial effect.

Application of biorelevant in vitro assays for the assessment and optimization of ASD-based formulations for pediatric patients.

Amorphous solid dispersions (ASD) have been a successful formulation strategy to overcome the poor aqueous solubility of many novel drugs, but the development of pediatric formulations presents a special challenge due to variable gastrointestinal conditions in children. It was the aim of this work to design and apply a staged biopharmaceutical test protocol for the in vitro assessment of ASD-based pediatric formulations. Ritonavir was used as a model drug with poor aqueous solubility.

Mpox outbreak 2022: an overview of all cases reported to the Cologne Health Department.

Purpose: The worldwide mpox outbreak starting in May 2022 marks the occurrence of another previously atypical infectious disease in Europe. This study's objective was to present a comprehensive overview based on the gathered data and to illustrate the approach of the Cologne Health Department to contain the mpox outbreak.

Methods: In this retrospective observational study, 368 individuals reported to the Cologne Health Department as PCR-positive for mpox were included.

Adherence to stay-at-home orders: awareness, implementation and difficulties of officially ordered quarantine measures in the context of the COVID-19 pandemic in Cologne - a retrospective cohort study.

Objectives: To estimate the awareness, implementation and difficulty of behavioural recommendations and their correlates in officially ordered domestic isolation and quarantine during the COVID-19 pandemic.

Design: Online retrospective cohort survey conducted from 12 December 2020 to 6 January 2021 as part of the Cologne-Corona Counselling and Support for Index and Contact Persons During the Quarantine Period study.

Setting: Administrative area of the city of Cologne, Germany.

Where is the greatest risk of COVID-19 infection? Findings from Germany's largest public health department, Cologne.

Background: SARS-CoV-2 has been spreading worldwide since late 2019. Before vaccines became available, exclusively non-pharmaceutical measures were used to prevent transmission of infection. Despite the fact that vaccinations are now available, it is still important to identify relevant transmission routes in order to contain the COVID-19- or further pandemics.

[Spatio-temporal distribution of COVID-19 in Cologne and associated socio-economic factors in the period from February 2020 to October 2021].

Background And Goals: Even in the early phase of the COVID-19 pandemic, which took a very different course globally, there were indications that socio-economic factors influenced the dynamics of disease spread, which from the second phase (September 2020) onwards particularly affected people with a lower socio-economic status. Such effects can also be seen within a large city. The present study visualizes and examines the spatio-temporal spread of all COVID-19 cases reported in Cologne, Germany (February 2020-October 2021) at district level and their possible association with socio-economic factors.

Coping strategies during legally enforced quarantine and their association to psychological distress level: a cross-sectional study.

Objectives: The non-pharmacological measures to contain the COVID-19 pandemic may lead to considerable psychological distress. The aim of the CoCo-Fakt study was to investigate possible coping strategies and their effects on psychological distress during legally enforced quarantine of infected persons (IPs) and their close contacts (CPs).

Study Design: This was a cross-sectional cohort study.

Implementing the Lolli-Method and pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools: a pilot project.

Purpose: School closures have been used as part of lockdown strategies to contain the spread of SARS-CoV-2, adversely affecting children's health and education. To ensure the accessibility of educational institutions without exposing society to the risk of increased transmissions, it is essential to establish SARS-CoV-2 testing strategies that are child-friendly, scalable and implementable in a daily school routine. Self-sampling using non-invasive saliva swabs combined with pooled RT-qPCR testing (Lolli-Method) has been proven to be a sensitive method for the detection of SARS-CoV-2.

Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children.

Systematic SARS-CoV-2 testing is a valuable tool for infection control and surveillance. However, broad application of high sensitive RT-qPCR testing in children is often hampered due to unpleasant sample collection, limited RT-qPCR capacities and high costs. Here, we developed a high-throughput approach ('Lolli-Method') for SARS-CoV-2 detection in children, combining non-invasive sample collection with an RT-qPCR-pool testing strategy.

Impact of physical activity on COVID-19-related symptoms and perception of physical performance, fatigue and exhaustion during stay-at-home orders.

Objectives: The measures used to contain the COVID-19 pandemic led to a significant reduction in physical activity. Due to the health benefits of exercise, recommendations were made for lockdown restrictions. Within the CoCo-Fakt study (Cologne-Corona counselling and support for index and contacts during the quarantine period), we aimed to determine how these recommendations were implemented, especially by individuals who were officially quarantined due to an infected persons (IPs) or as close contacts (CPs), and how this affected their physical and psychological condition.

Changes in Alcohol Consumption, Eating Behaviors, and Body Weight during Quarantine Measures: Analysis of the CoCo-Fakt Study.

Introduction: Public health measures enacted to reduce COVID-19 transmission have affected individuals' lifestyles, mental health, and psychological well-being. To date, little is known how stay-at-home orders have influenced the eating behaviors, weight development, and alcohol consumption of quarantined persons. The CoCo-Fakt cohort study analyzed these parameters and their association with psychological distress and coping strategies.

Breakthrough infections with the SARS-CoV-2 Delta variant: vaccinations halved transmission risk.

Objectives: The SARS-CoV-2 Delta variant (B.1.617.

COVID-19 Breakthrough Infections and Transmission Risk: Real-World Data Analyses from Germany's Largest Public Health Department (Cologne).

Background And Methods: Vaccination is currently considered the most successful strategy for combating the SARS-CoV-2 virus. According to short-term clinical trials, protection against infection is estimated to reach up to 95% after complete vaccination (≥14 days after receipt of all recommended COVID-19 vaccine doses). Nevertheless, infections despite vaccination, so-called breakthrough infections, are documented.