Search Results (5)

Background: Avian influenza (AI), caused by orthomyxoviruses, is a globally significant disease affecting avian and non-avian species. It manifests in two variants, according to the two biovariants of the virus differentiated as highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) strains, both of which compromise animal welfare, reduce productivity, and cause substantial economic loss. The zoonotic potential of HPAI strains, particularly the currently dominant clade 2.3.4.4b, raises concerns about public health and epidemic risks. This review assesses the results of current vaccine trials targeting HPAI clade 2.3.4.4b, emphasizing these studies because most outbreak strains in domestic poultry currently belong to this dominant clade. Methods: Multiple scientific databases comprised reports of research trials on vaccine efficacy against HPAI clade 2.3.4.4b. The Boolean term “Clade 2.3.4.4b AND vaccine” was entered into the following databases: PubMed, PubAg, Scopus, Cochrane Library, and ScienceDirect. Results: The resulting papers were analyzed. Studies revealed that antigenic similarity between vaccine and field strains enhances protective efficacy (PE), reduces viral shedding, and improves hemagglutination inhibition titers. While multivalent vaccines showed potential, results were inconsistent and varied depending on strain compatibility. Single-dose vaccines may provide sufficient PE for poultry, though ducks and geese often require multiple doses, and long-term PE is yet unknown. It was discovered that vector vaccines can provide appropriate PE against clade 2.3.4.4.b. Conclusions: Further analysis is needed as their effects may be short-lived, and subsequent doses may be required. Limited research exists on the long-term efficacy of these vaccines and their effectiveness in many avian species. Addressing these gaps is crucial for optimizing vaccination strategies. A re-evaluation of vaccination strategies is recommended but essential to implement adequate biosecurity measures on in poultry farms. This review synthesizes current evidence and may assist veterinarians and authorities in deciding whether to apply or license vaccines to reduce economic losses caused by AI. Full article

This study examines the effects of metformin on brain functions focusing on the variability of the results reported in the literature. While some studies suggest that metformin may have neuroprotective effects in diabetic patients, others report an insignificant impact of metformin on cognitive function, or even a negative effect. We propose that this inconsistency may be due to intrinsic cellular-level variability among individuals, which we term “biovariance”. Biovariance persists even in demographically homogeneous samples due to complex and stochastic biological processes. Additionally, the complex metabolic actions of metformin, including its influence on neuroenergetics and neuronal survival, may produce different effects depending on individual metabolic characteristics. Full article

(1) Background: High-dose chemotherapy (HDCT) before autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML) patients predominantly combines busulfan with cyclophosphamide or melphalan. Treosulfan compares favorably regarding lower inter-individual bioavailability and neurotoxicity, but so far, had not been studied before ASCT in AML. (2) Methods: This single-center study investigated AML patients undergoing ASCT in CR1 between November 2017 and September 2020. The first 16 patients received busulfan 16 mg/kg b.w. (days −5 to −2) and melphalan 140 mg/m² (day −1) (BuMel). In a subsequent (TreoMel) cohort, 20 patients received treosulfan 14 g/m² (days −4 to −2) and melphalan. Plasma concentrations of busulfan and treosulfan were determined by mass spectrometry. (3) Results: Neutrophil engraftment and platelet recovery were similar, and PFS and OS were comparable. In only the BuMel cohort, patients reported central nervous toxicities, including seizures (6%) and encephalopathy (12%). The mean AUC for busulfan was 1471.32 μM*min, and for treosulfan it was 836.79 mg/L*h, with ranges of 804.1–2082 μM*min and 454.2–1402 mg/L*h. The peak values for busulfan ranged between 880.19–1734 μg/L and for treosulfan between 194.3–489.25 mg/L. (4) Conclusions: TreoMel appears to be safe and effective for pre-ASCT treatment in AML patients. Due to considerable interindividual biovariability, pharmacologic monitoring may also be warranted for the use of treosulfan. Full article

(1) Background: With vaccination and new variants of SARS-CoV-2 on the horizon, efficient testing in schools may enable prevention of mass infection outbreaks, keeping schools safe places and buying time until decisions on feasibility and the necessity of vaccination in children and youth are made. We established, in the course of the WICOVIR (Where Is the COrona VIRus) study, that gargle-based pool-PCR testing offers a feasible, efficient, and safe testing system for schools in Germany when applied by central university laboratories. (2) Objectives: We evaluated whether this approach can be implemented in different rural and urban settings. (3) Methods: We assessed the arrangements required for successful implementation of the WICOVIR approach in a variety of settings in terms of transport logistics, data transfer and pre-existing laboratory set-up, as well as the time required to establish the set-up. (4) Results: We found that once regulatory issues have been overcome, all challenges pertaining to logistics, data transfer, and laboratory testing on different platforms can be solved within one month. Pooling and depooling of samples down to the individual test result were achievable within one working day in all settings. Local involvement of the community and decentralized set-ups were keys for success. (5) Conclusion: The WICOVIR gargle-based pool-PCR system is so robust and simple that it can be implemented within one month in all settings now or in future pandemics. Full article

In recent years, onco-metabolites like D-2-hydroxyglutarate, which is produced in isocitrate dehydrogenase-mutated tumors, have gained increasing interest. Here, we report a metabolite in human specimens that is closely related to 2-hydroxyglutarate: the intramolecular ester of 2-hydroxyglutarate, 2-hydroxyglutarate-γ-lactone. Using ¹³C₅-L-glutamine tracer analysis, we showed that 2-hydroxyglutarate is the endogenous precursor of 2-hydroxyglutarate-lactone and that there is a high exchange between these two metabolites. Lactone formation does not depend on mutated isocitrate dehydrogenase, but its formation is most probably linked to transport processes across the cell membrane and favored at low environmental pH. Furthermore, human macrophages showed not only striking differences in uptake of 2-hydroxyglutarate and its lactone but also in the enantiospecific hydrolysis of the latter. Consequently, 2-hydroxyglutarate-lactone may play a critical role in the modulation of the tumor microenvironment. Full article