Real-time public health communication of local SARS-CoV-2 genomic epidemiology.

Genomic epidemiology can provide a unique, real-time understanding of SARS-CoV-2 transmission patterns. Yet the potential for genomic analyses to guide local policy and community-based behavioral decisions is limited because they are often oriented towards specially trained scientists and conducted on a national or global scale. Here, we propose a new paradigm: Phylogenetic analyses performed on a local level (municipal, county, or state), with results communicated in a clear, timely, and actionable manner to strengthen public health responses. We believe that presenting results rapidly, and tailored to a non-expert audience, can serve as a template for effective public health response to COVID-19 and other emerging viral diseases.

Process analytical technology in Downstream-Processing of Drug Substances- A review.

Process Analytical Technology (PAT) has revolutionized pharmaceutical manufacturing by providing real-time monitoring and control capabilities throughout the production process. This review paper comprehensively examines the application of PAT methodologies specifically in the production of solid active pharmaceutical ingredients (APIs). Beginning with an overview of PAT principles and objectives, the paper explores the integration of advanced analytical techniques such as spectroscopy, imaging modalities and others into solid API substance production processes. Novel developments in in-line monitoring at academic level are also discussed. Emphasis is placed on the role of PAT in ensuring product quality, consistency, and compliance with regulatory requirements. Examples from existing literature illustrate the practical implementation of PAT in solid API substance production, including work-up, crystallization, filtration, and drying processes. The review addresses the quality and reliability of the measurement technologies, aspects of process implementation and handling, the integration of data treatment algorithms and current challenges. Overall, this review provides valuable insights into the transformative impact of PAT on enhancing pharmaceutical manufacturing processes for solid API substances.

Temperature cycling-induced formation of crystalline coatings.

The surface of particles is the hotspot of interaction with their environment and is therefore a major target for particle engineering. Particles with tailored coatings are greatly desired for a range of different applications. Amorphous coatings applied via film coating or microencapsulation have frequently been described in the pharmaceutical context and usually result in homogeneous surfaces. In the present study we have been exploring the feasibility of coating core particles with crystalline substances, a matter that has rarely been investigated. The expansion of the range of possible coating materials to include small organic molecules enables completely new product properties to be achieved. We present an approach based on temperature cycles performed in a tubular crystallizer to result in engineered crystalline coatings on excipient core particles. By manipulating the process settings and by the choice of coating substance we are able to tailor surface roughness, topography as well as surface chemistry. Benefits of our approach are demonstrated by using resulting particles as carriers in dry-powder-inhaler formulations. Depending on the resulting surface chemistry and surface roughness, coated carrier particles show varying fitness for delivering the model API salbutamol sulphate to the lung.

Fifteen years of the cologne medical model study course: has the expectation of increasing student interest in general practice specialization been fulfilled?

Background: The 2002 Medical Licensure Act gave German universities certain freedoms for reforming their medical degree courses. The Medical Faculty of the University of Cologne took advantage of this opportunity and introduced a model study course in the winter semester 2003/04 through §41 of the Medical Licensure Act. One of the main reasons for this was that back then there was an increasing shortage of doctors in clinical curative medicine and GP primary care. This study investigates whether the introduction of the Cologne Model Study Course (MSG) can show stronger interest in curative medical work (especially General Practice) compared to students of the standard degree course (RSG). Methodology: The proof of added value was examined through graduate surveys conducted at the University of Cologne and through the proportion of students who completed the PY elective rotation "General Practice". The students of the standard degree course (start of studies prior to winter semester 2003/2004) were compared with students of the model study course (start of studies from winter semester 2003/04 onwards). Measurements were carried out using descriptive frequency tables and correlation analyzes according to Spearman. Results: The students' interest in curative medicine was already high (91%) even before the model study course was introduced and increased only slightly (to 91.9%). There is also only a slight increase in specialization in General Practice (RSG=5.9% vs. MSG=9.2%). However, selection of rotations in General Practice was significantly increased (RSG=1.9% vs. MSG=3.4%, r=0.046 **, p<0.005). Conclusion: The Cologne Model Study Course in Human Medicine has increased awareness of the subject of General Practice among students through a large number of curricular changes. The fact that only marginal effects can be demonstrated shows once more the strong dependence of choosing General Medicine as a career path on other factors (such as gender or the presence of positive role models) and emphasizes the necessity of promoting General Practice student education not only through increased curricular mapping but by additional innovative concepts to maximize the status of General Practice from the perspective of students.

Crystal Shape Modification via Cycles of Growth and Dissolution in a Tubular Crystallizer.

Besides size and polymorphic form, crystal shape takes a central role in engineering advanced solid materials for the pharmaceutical and chemical industries. This work demonstrates how multiple cycles of growth and dissolution can manipulate the habit of an acetylsalicylic acid crystal population. Considerable changes of the crystal habit could be achieved within minutes due to rapid cycling, i.e., up to 25 cycles within <10 min. The required fast heating and cooling rates were facilitated using a tubular reactor design allowing for superior temperature control. The face-specific interactions between solvent and the crystals' surface result in face-specific growth and dissolution rates and hence alterations of the final shape of the crystals in solution. Accurate quantification of the crystal shapes was essential for this work, but is everything except simple. A commercial size and shape analyzer had to be adapted to achieve the required accuracy. Online size, and most important shape, analysis was achieved using an automated microscope equipped with a flow-through cell, in combination with a dedicated image analysis routine for particle tracking and shape analysis. Due to the implementation of this analyzer, capable of obtaining statistics on the crystals' shape while still in solution (no sampling and manipulation required), the dynamic behavior of the size shape distribution could be studied. This enabled a detailed analysis of the solvent's effect on the change in crystal habit.

Crystal Engineering in Continuous Plug-Flow Crystallizers.

Size, shape, and polymorphic form are the critical attributes of crystalline particles and represent the major focus of today's crystallization process design. This work demonstrates how crystal properties can be tuned efficiently in solution via a tubular crystallizer that facilitates rapid temperature cycling. Controlled crystal growth, dissolution, and secondary nucleation allow a precise control of the crystal size and shape distribution, as well as polymorphic composition. Tubular crystallizers utilizing segmented flow such as the one presented in our work can provide plug flow characteristics, fast heating and cooling, allowing for rapid changes of the supersaturation. This makes them superior for crystal engineering over common crystallizers. Characterization of particle transport, however, revealed that careful selection of process parameters, such as tubing diameter, flow rates, solvents, etc., is crucial to achieve the full benefits of such reactors.

A rare differential diagnosis in dysphagia: wound botulism.

The incidence of wound botulism is increasing dramatically among intravenous drug users. Efficient intensive care and early treatment with antitoxin is essential to avoid lethal courses. The clinical picture of botulism is of descending, symmetric, flaccid paralysis. Early symptoms include cranial nerve palsies resulting in blurred vision and diplopia, difficulty in focusing, ptosis, facial weakness, dysphagia, dysphonia, and dysarthria. Because patients presenting with dysarthria and dysphagia will often be seen by an ear, nose and throat specialist initially, this rare but upcoming neurologic disease must be considered in the differential diagnoses.

Continuous Crystallization of Proteins in a Tubular Plug-Flow Crystallizer.

Protein crystals have many important applications in many fields, including pharmaceutics. Being more stable than other formulations, and having a high degree of purity and bioavailability, they are especially promising in the area of drug delivery. In this contribution, the development of a continuously operated tubular crystallizer for the production of protein crystals has been described. Using the model enzyme lysozyme, we successfully generated product particles ranging between 15 and 40 µm in size. At the reactor inlet, a protein solution was mixed with a crystallization agent solution to create high supersaturations required for nucleation. Along the tube, supersaturation was controlled using water baths that divided the crystallizer into a nucleation zone and a growth zone. Low flow rates minimized the effect of shear forces that may impede crystal growth. Simultaneously, a slug flow was implemented to ensure crystal transport through the reactor and to reduce the residence time distribution.

Sinuorbital complications after intranasal cocaine abuse.

Proptosis and double vision were the presenting signs in a case of chronic orbital inflammation generated by osteolytic destruction of the sinuorbital barriers due to intranasal abuse of cocaine. The pathophysiologic background and reports from the literature dealing with orbital involvement in this condition are discussed.

Ciliogenesis in submersion and suspension cultures of human nasal epithelial cells.

Human nasal respiratory cells lose cilia in submerged cultures. This study compares the effect of extracellular matrix (ECM) molecules of the basal lamina on ciliogenesis in submerged cell cultures to ECM-free suspension cultures. Respiratory mucosa of nasal turbinates was the routine source for the cultures of nasal epithelial cells. For the submersion cultures, enzymatically isolated cells were seeded either on a layer of lethally irradiated ((60)Co, 60 Gy) murine 3T3-feeder fibroblasts or on an ECM-coated culture flask. For suspension cultures, the flasks were rotated for 3 days after cell seeding. In ECM-coated flasks, epithelial cell attachment and confluence was promoted and always much better than in cultures on a feeder layer. Respiratory cells lost cilia during the first 5 weeks in submerged cultures. Genesis of new, actively beating cilia was seen after 5-6 weeks when plastic culture dishes were coated with ECM molecules. Cells grown on uncoated plastic dishes together with 3T3-fibroblasts showed no ciliogenesis. Spheroids of epithelial cells in suspension cultures lost cilia during the 1st week and developed new cilia after 1-2 weeks in vitro. Our results suggest that ECM molecules are not the only signal for ciliary differentiation of respiratory cells in vitro, because suspension cultures are ECM free. However, the presence of ECM molecules in submerged cell cultures promotes the attachment and early confluence of seeded epithelial cells with a high density of cuboidal epithelial cells. The specific cellular shape and intense intercellular contact of these cuboidal cells may be among the most important signals inducing terminal differentiation and ciliogenesis.