Opportunities of topical drug products in a changing dermatological landscape.

Despite the prevalence and the impact on quality of life of dermatological indications, drug products to treat such conditions have rarely been blockbusters. The prevailing perception of a limited commercial potential of dermatological drug products has restricted innovation and encouraged a more conservative development approach. For example, the focus was on repurposing/reformulation of existing active pharmaceutical ingredients (APIs) specifically for the topical delivery route.

Rational Design of Topical Semi-Solid Dosage Forms-How Far Are We?

Specific aspects of semi-solid dosage forms for topical application include the nature of the barrier to be overcome, aspects of susceptibility to physical and chemical instability, and a greater influence of sensory perception. Advances in understanding the driving forces of skin penetration as well as the design principles and inner structure of formulations, provide a good basis for the more rational design of such dosage forms, which still often follow more traditional design approaches. This review analyses the opportunities and constraints of rational formulation design approaches in the industrial development of new topical drugs.

New Complexes of Antimony(III) with Tridentate ,,-Ligands (E = O, S, Se, Te, NH, NMe) Derived from -Methyldiethanolamine.

We synthesized a series of new antimony(III) compounds by reaction of Sb(OEt) with organic ligands of the type E(CH-CH-OH), with E = NH, NMe, O, S, Se, and Te. The synthesized compounds have the general composition [E(CH-CH-O)]Sb(OEt). For comparison, the compound (O-CH-CH-S)Sb(OEt) was prepared.

9-(Pyrrolidinium-1-yl)-9-boranuidabi-cyclo-[3.3.1]nona-ne.

The title compound, CHBN, is an adduct formed from 9-borabi-cyclo-[3.3.1]nonane (9-BBN) and pyrrolidine.

Two polymorphs of ,'-diphenyl-2-[1-(propyl-amino)-ethyl-idene]propanedi-amide.

Two polymorphs of the title compound, CHNO, have been isolated. Polymorph () crystallizes in the monoclinic space group / and polymorph () in the tetra-gonal space group /. The main difference between the two polymorphs on the mol-ecular level is the orientation of the -propyl group.

()--Phenyl--(phenyl-carbamo-yl)-3-[prop-yl(tri-methyl-sil-yl)amino]-acryl-amide chloro-form hemisolvate.

The title compound, CHNOSi·0.5CHCl, crystallizes in the the triclinic space group with two host mol-ecules and one chloro-form mol-ecule in the asymmetric unit. The core of the mol-ecule consists of a urea unit bound to a 3-amino-acryloyl group.

Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray - AM-301.

Objective: The present work provides characterization of rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray (AM-301), its nasal residence time, distribution, safety and tolerability.

Significance: The nasal epithelium is a portal of entry for allergens and primary infection by airborne pathogens. Non-pharmacological interventions, which enhance physical and biological barriers, protect against allergens and pathogens without drug-related side effects.

Real-time intelligent classification of COVID-19 and thrombosis via massive image-based analysis of platelet aggregates.

Microvascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images.

Image-based cell sorting using focused travelling surface acoustic waves.

Sorting cells is an essential primary step in many biological and clinical applications such as high-throughput drug screening, cancer research and cell transplantation. Cell sorting based on their mechanical properties has long been considered as a promising label-free biomarker that could revolutionize the isolation of cells from heterogeneous populations. Recent advances in microfluidic image-based cell analysis combined with subsequent label-free sorting by on-chip actuators demonstrated the possibility of sorting cells based on their physical properties.

Perturbations of mesenchymal stromal cells after allogeneic hematopoietic cell transplantation predispose for bone marrow graft-versus-host-disease.

Functional impairment of the bone marrow (BM) niche has been suggested as a major reason for prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplantation (alloHCT). Because mesenchymal stromal cells (MSCs) serve as multipotent progenitors for several niche components in the BM, they might play a key role in this process. We used collagenase digested trephine biopsies to directly quantify MSCs in 73 patients before (n = 18) and/or after alloHCT (n = 65).

Development of a new, fully automated system for electron backscatter diffraction (EBSD)-based large volume three-dimensional microstructure mapping using serial sectioning by mechanical polishing, and its application to the analysis of special boundaries in 316L stainless steel.

We report the development of a fully automatic large-volume 3D electron backscatter diffraction (EBSD) system (ELAVO 3D), consisting of a scanning electron microscope (ZEISS crossbeam XB 1540) with a dedicated sample holder, an adapted polishing automaton (Saphir X-change, QATM), a collaborative robotic arm (Universal Robots UR5), and several in-house built devices. The whole system is orchestrated by an in-house designed software, which is also able to track the process and report errors. Except for the case of error, the system runs without any user interference.

Why do people consent to receiving SARS-CoV-2 vaccinations? A representative survey in Germany.

Objective: To answer the question: Why do people consent to being vaccinated with novel vaccines against SARS-CoV-2?

Design: Representative survey.

Setting: Online panel.

Participants: 1032 respondents of the general German population.

Long-term effects of Pfizer-BioNTech COVID-19 vaccinations on platelets.

There is a global concern about the safety of COVID-19 vaccines associated with platelet function. However, their long-term effects on overall platelet activity remain poorly understood. Here we address this problem by image-based single-cell profiling and temporal monitoring of circulating platelet aggregates in the blood of healthy human subjects, before and after they received multiple Pfizer-BioNTech (BNT162b2) vaccine doses over a time span of nearly 1 year.

Intelligent sort-timing prediction for image-activated cell sorting.

Intelligent image-activated cell sorting (iIACS) has enabled high-throughput image-based sorting of single cells with artificial intelligence (AI) algorithms. This AI-on-a-chip technology combines fluorescence microscopy, AI-based image processing, sort-timing prediction, and cell sorting. Sort-timing prediction is particularly essential due to the latency on the order of milliseconds between image acquisition and sort actuation, during which image processing is performed.

Intelligent image-activated sorting of Chlamydomonas reinhardtii by mitochondrial localization.

Organelle positioning in cells is associated with various metabolic functions and signaling in unicellular organisms. Specifically, the microalga Chlamydomonas reinhardtii repositions its mitochondria, depending on the levels of inorganic carbon. Mitochondria are typically randomly distributed in the Chlamydomonas cytoplasm, but relocate toward the cell periphery at low inorganic carbon levels.

Reconstructing dual-phase nanometer scale grains within a pearlitic steel tip in 3D through 4D-scanning precession electron diffraction tomography and automated crystal orientation mapping.

The properties of polycrystalline materials are related to their microstructures and hence a complete description, including size, shape, and orientation of the grains, is necessary to understand the behavior of materials. Here, we use Scanning Precession Electron Diffraction (SPED) in the Transmission Electron Microscope (TEM) combined with a tilt series to reconstruct individual grains in 3D within a polycrystalline dual-phase cold wire-drawn pearlitic steel sample. Nanoscale ferrite grains and intragranular cementite particles were indexed using an Automated Crystallographic Orientation Mapping (ACOM) tool for each tilt dataset.

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium.

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of five ChAc patients compared to healthy controls during up to 1-year individual off-label treatment with the tyrosine kinase inhibitor dasatinib or several weeks with lithium.

Topical Film-Forming Solid Solutions for Enhanced Dermal Delivery of the Retinoid Tazarotene.

Topical film-forming solutions (FFSs) show considerable potential for dermal delivery of an API. Through a mechanism of in situ film formation upon solvent evaporation, they may improve skin delivery by prolonging substantivity on the skin, by establishing a transient supersaturation, and/or by enhancing solubility through the formation of a solid dispersion in the resulting film. This work aimed at developing an FFS for topical application with enhanced skin delivery.

Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph).

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC).

Deep imaging flow cytometry.

Imaging flow cytometry (IFC) has become a powerful tool for diverse biomedical applications by virtue of its ability to image single cells in a high-throughput manner. However, there remains a challenge posed by the fundamental trade-off between throughput, sensitivity, and spatial resolution. Here we present deep-learning-enhanced imaging flow cytometry (dIFC) that circumvents this trade-off by implementing an image restoration algorithm on a virtual-freezing fluorescence imaging (VIFFI) flow cytometry platform, enabling higher throughput without sacrificing sensitivity and spatial resolution.

Label-free imaging flow cytometry for analysis and sorting of enzymatically dissociated tissues.

Biomedical research relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells' properties and should be avoided, especially when purifying cells for clinical applications. A promising alternative is the label-free identification of cells based on physical properties.

Machine learning assisted real-time deformability cytometry of CD34+ cells allows to identify patients with myelodysplastic syndromes.

Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to detect shifts of cellular properties of entire populations.

Reactive wear protection through strong and deformable oxide nanocomposite surfaces.

Wear-related energy and material loss cost over 2500 Billion Euro per year. Traditional wisdom suggests that high-strength materials reveal low wear rates, yet, their plastic deformation mechanisms also influence their wear performance. High strength and homogeneous deformation behavior, which allow accommodating plastic strain without cracking or localized brittle fracture, are crucial for developing wear-resistant metals.