Antibacterial property alterations induced by low zinc content in laser-structured brass

Brass, along with other copper-based alloys, exhibits advantageous antibacterial properties that can be further enhanced by altering the surface topography to increase bacterial adhesion. This enhancement is achievable through a higher contact area created by precise periodic structures, each approximately the size of a single bacterial cell. One method for generating these structures is ultrashort pulsed direct laser interference patterning (USP-DLIP). However, this process may induce chemical alterations in addition to topographical changes, depending on the substrate’s composition. To mitigate unfavorable chemical alterations, brass with a 15% zinc content was selected for this study. The antibacterial effectiveness of the modified surfaces was tested against Escherichia coli, providing initial insights into the interaction between bacteria and the substrate. The results indicate that modified brass with a 15% zinc content shows improved antibacterial activity. Overall, this research demonstrates that by modifying a surface with the appropriate chemical composition, effective bacterial elimination through contact can be achieved

Spray drying of a zinc complexing agent for inhalation therapy of pulmonary fibrosis

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 ◦C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis

The RNA binding protein IGF2BP2/IMP2 alters the cargo of cancer cell-derived extracellular vesicles supporting tumor-associated macrophages

Background Tumor cells release extracellular vesicles (EVs) that contribute to the polarization of macrophages towards tumor-associated macrophages (TAMs). High expression levels of the RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in the clinic. However, there is a lack of understanding of whether IMP2 afects the cargo of cancer cell-derived EVs, thereby modulating macrophage polarization. Methods EVs were isolated from IMP2-expressing HCT116 parental cells (WT) and CRISPR/Cas9 IMP2 knockout (KO) cells. EVs were characterized according to MISEV guidelines, microRNA cargo was assessed by microRNA-Seq, and the protein cargo was analyzed by proteomics. Primary human monocyte-derived macrophages (HMDMs) were polarized by EVs, and the expression of genes and surface markers was assessed using qPCR and fow cytometry, respectively. Morphological changes of macrophages, as well as the migratory potential of cancer cells, were assessed by the Incucyte® system and macrophage matrix degradation potential by zymography. Changes in the meta‑ bolic activity of macrophages were quantifed using a Seahorse® analyzer. For in vivo studies, EVs were injected into the yolk sac of zebrafsh larvae, and macrophages were isolated by fuorescence-activated cell sorting. Results EVs from WT and KO cells had a similar size and concentration and were positive for 25 vesicle mark‑ ers. The expression of tumor-promoting genes was higher in macrophages polarized with WT EVs than KO EVs, while the expression of TNF and IL6 was reduced. A similar pattern was observed in macrophages from zebrafsh larvae treated in vivo. WT EV-polarized macrophages showed a higher abundance of TAM-like surface markers, higher matrix degrading activity, as well as a higher promotion of cancer cell migration. MicroRNA-Seq revealed a signif‑ cant diference in the microRNA composition of WT and KO EVs, particularly a high abundance of miR-181a-5p in WT EVs, which was absent in KO EVs. Inhibitors of macropinocytosis and phagocytosis antagonized the delivery of miR181a-5p into macrophages and the downregulation of the miR-181a-5p target DUSP6. Proteomics data showed diferences in protein cargo in KO vs. WT EVs, with the diferentially abundant proteins mainly involved in metabolic pathways. WT EV-treated macrophages exhibited a higher basal oxygen consumption rate and a lower extracellular acidifcation rate than KO EV-treated cells. Conclusion Our results show that IMP2 determines the cargo of EVs released by cancer cells, thereby modulating the EVs’ actions on macrophages. Expression of IMP2 is linked to the secretion of EVs that polarize macrophages towards a tumor-promoting phenotype

Erosion protective properties of the enamel pellicle in-situ

Objectives: Previous studies on short- and long-term pellicles showed that the enamel pellicle provides partial protection against erosion. The aim of the present study was to investigate the protective properties of clinically relevant pellicles formed within 2 to 24 h. The hypothesis was that factors such as pellicle formation time, intraoral location, and acidic challenge severity would not influence the erosion-protective properties of the pellicle. Methods: Six subjects participated in the study. Bovine enamel specimens were prepared and intraorally exposed at buccal or palatal sites for 2, 6, 12, and 24 h to allow pellicle formation, followed by erosion using 0.1 % or 1 % citric acid. Calcium release and surface microhardness were measured, and specimens were analysed using scanning and transmission electron microscopy. Quantitative data were statistically analysed with threeway ANOVA and Tuckey’s multiple comparison test (p = 0.05). Results: Pellicle formation time and intraoral location did not significantly influence the erosion-protective properties of the pellicle, while citric acid concentration significantly affected enamel erosion. The pellicle thickness increased with longer formation times and on buccal sites, but decreased or was entirely removed following treatment with 0.1 % or 1 % citric acid, respectively. The enamel surface exhibited a characteristic erosion pattern. Conclusions: This study underscores the importance of investigating pellicle properties within the critical 2- to 24-h timeframe and highlights the significance of pellicle thickness in acid resistance. Clinical significance: These findings provide valuable insights into the factors influencing the protective properties of enamel pellicles and could guide preventive measures in dental practice

Vector analysis of corneal astigmatism in cataractous eyes based on IOLMaster 700 biometry

Purpose The purpose of this study was to investigate the effect of the corneal back surface by comparing the keratometric astigmatism (K, derived from the corneal front surface) of a modern optical biometer against astigmatism of Total Keratometry (TK, derived from both corneal surfaces) in a large population with cataractous eyes. The results were then used to define linear prediction models to map K to TK. Methods From a large dataset containing bilateral biometric measurements (IOLMaster 700) in 9736 patients prior to cataract surgery, the total corneal astigmatism was decomposed into vectors for K, corneal back surface (BS), and TK. A multivariate prediction model (MV), simplified model with separation of vector components (SM) and a constant model (CM) were defined to map K to TK vector components. Results The K centroid (X/Y) showed some astigmatism with-the-rule (0.1981/-0.0211 dioptre (dpt)) whereas the TK centroid was located around zero (-0.0071/-0.0381 dpt against-the-rule) and the BS centroid showed systematic astigmatism against-the-rule (-0.2367/-0.0145 dpt). The respective TK–K centroid was located at -0.2052/-0.0302 dpt. The MV model showed the same performance (i.e. mean absolute residuum) as the SM did (0.1098 and 0.1099 dpt respectively) while the CM performed only slightly worse (0.1121 dpt mean absolute residuum). Conclusion In cases where tomographic data are unavailable statistical models could be used to consider the overall contribution of the back surface to the total corneal astigmatism. Since the performance of the CM is sufficiently close to that of MV and SM we recommend using the CM which can be directly considered e.g. as surgically induced astigmatism

Unlocking the Potential: immune functions of oligodendrocyte precursor cells

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances have illuminated their multifaceted nature including their emerging immune functions. This review seeks to shed light on the immune functions exhibited by OPCs, spanning from phagocytosis to immune modulation and direct engagement with immune cells across various pathological scenarios. Comprehensive understanding of the immune functions of OPCs alongside their other roles will pave the way for targeted therapies in neurological disorders

Efficacy of Simulator-Based Slit Lamp Training for Medical Students: A Prospective, Randomized Trial

Simulation training has an important role in medical education. In ophthalmology, simulation-based training has been shown to be significantly effective for surgical and diagnostic training in direct and indirect ophthalmoscopy. In this study, we analysed the effects of simulator-based slit lamp training

A physiologically-based pharmacokinetic precision dosing approach to manage dasatinib drug-drug interactions

Dasatinib, a second-generation tyrosine kinase inhibitor, is approved for treating chronic myeloid and acute lymphoblastic leukemia. As a sensitive cytochrome P450 (CYP) 3A4 substrate and weak base with strong pH-sensitive solubility, dasatinib is susceptible to enzyme-mediated drug–drug interactions (DDIs) with CYP3A4 perpetrators and pH-dependent DDIs with acid-reducing agents. This work aimed to develop a whole-body physiologically-based pharmacokinetic (PBPK) model of dasatinib to describe and predict enzyme-mediated and pH-dependent DDIs, to evaluate the impact of strong and moderate CYP3A4 inhibitors and inducers on dasatinib exposure and to support optimized dasatinib dosing. Overall, 63 plasma profiles from perorally administered dasatinib in healthy volunteers and cancer patients were used for model development. The model accurately described and predicted plasma profiles with geometric mean fold errors (GMFEs) for area under the concentration–time curve from the first to the last timepoint of measurement (AUClast) and maximum plasma concentration (Cmax) of 1.27 and 1.29, respectively. Regarding the DDI studies used for model development, all (8/8) predicted AUClast and Cmax ratios were within twofold of observed ratios. Application of the PBPK model for dose adaptations within various DDIs revealed dasatinib dose reductions of 50%–80% for strong and 0%–70% for moderate CYP3A4 inhibitors and a 2.3–3.1-fold increase of the daily dasatinib dose for CYP3A4 inducers to match the exposure of dasatinib administered alone. The developed model can be further employed to personalize dasatinib therapy, thereby help coping with clinical challenges resulting from DDIs and patientrelated factors, such as elevated gastric pH

Analytical study of a generalised Dirichlet–Neumann operator and application to three-dimensional water waves on Beltrami flows

We consider three-dimensional doubly periodic steady water waves with vorticity, under the action of gravity and surface tension; in particular we consider so-called Beltrami flows, for which the velocity field and the vorticity are collinear. We adapt a recent formulation of the corresponding problem for localised waves which involves a generalisation of the classical Dirichlet–Neumann operator. We study this operator in detail, extending some well-known results for the classical Dirichlet–Neumann operator, such as the Taylor expansion in homogeneous powers of the wave profile, the computation of its differential and the asymptotic expansion of its associated symbol. A new formulation of the problem as a single equation for the wave profile is also presented and discussed in a similar vein. As an application of these results we prove existence of doubly periodic gravity-capillary steady waves and construct approximate doubly periodic gravity steady waves

Treatment of chronic syndesmotic rupture – What is the current evidence?

Akute Verletzungen im oberen Sprunggelenk ko¨nnen langfristig in bis zu 30% der Fa¨lle zu chronischen Instabilita¨ten fu¨hren. Ein anatomisch widerhergestelltes distales Tibiofibulargelenk stellt einen wesentlichen Faktor fu¨r das klinische Outcome von Patienten dar. Auffa¨lligkeiten in der klinischen Untersuchung bei Verdacht auf eine chronische Syndesmosenverletzung sollten zur weiteren Diagnostik fu¨hren. Stabile La¨sion sollte mittels konservativer Maßnahmen therapiert werden. Zur operativen Versorgung der instabilen chronischen Syndesmosenverletzung ist eine große Vielfalt an Therapiemethoden in der Literatur beschrieben. Die publizierten Operationsmethoden reichen vom arthroskopischen De´bridement bis hin zu komplexen operativen Versorgungen mittels Syndesmosenrekonstruktion oder auch der tibiofibula¨rer Fusion. Die Evidenz der verschiedenen Therapiemethoden ist gering und beruht maßgeblich auf Expertenempfehlungen. Zum aktuellen Zeitpunkt kann kein Therapieregime uneingeschra¨nkt bevorzugt empfohlen werden (2023).Acute injuries to the ankle joint can lead to chronic instability in up to 30% of cases in the long term. An anatomically restored distal tibiofibular joint is a significant factor in the clinical outcome of patients. Abnormalities in the clinical examination when a chronic syndesmosis injury is suspected should lead to further diagnostics. Stable lesions should be treated with conservative measures. A wide variety of treatment methods have been described in the literature for the surgical treatment of unstable chronic syndesmosis injuries. The published surgical methods range from arthroscopic debridement to complex surgical treatment using syndesmosis reconstruction or tibiofibular fusion. The evidence for the various treatment methods is limited and is largely based on expert recommendations. At the present time, no treatment regimen can be recommended without reservation (2023)