Volumetric Printing Across Melt Electrowritten Scaffolds Fabricates Multi-Material Living Constructs with Tunable Architecture and Mechanics.

Major challenges in biofabrication revolve around capturing the complex, hierarchical composition of native tissues. However, individual 3D printing techniques have limited capacity to produce composite biomaterials with multi-scale resolution. Volumetric bioprinting recently emerged as a paradigm-shift in biofabrication. This ultrafast, light-based technique sculpts cell-laden hydrogel bioresins into 3D structures in a layerless fashion, providing enhanced design freedom over conventional bioprinting. However, it yields prints with low mechanical stability, since soft, cell-friendly hydrogels are used. Herein, the possibility to converge volumetric bioprinting with melt electrowriting, which excels at patterning microfibers, is shown for the fabrication of tubular hydrogel-based composites with enhanced mechanical behavior. Despite including non-transparent melt electrowritten scaffolds in the volumetric printing process, high-resolution bioprinted structures are successfully achieved. Tensile, burst, and bending mechanical properties of printed tubes are tuned altering the electrowritten mesh design, resulting in complex, multi-material tubular constructs with customizable, anisotropic geometries that better mimic intricate biological tubular structures. As a proof-of-concept, engineered tubular structures are obtained by building trilayered cell-laden vessels, and features (valves, branches, fenestrations) that can be rapidly printed using this hybrid approach. This multi-technology convergence offers a new toolbox for manufacturing hierarchical and mechanically tunable multi-material living structures.

Analysis of the Virus SARS-CoV-2 as a Potential Bioweapon in Light of International Literature.

INTRODUCTION: As of early 2022, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic still represents a worldwide medical emergency situation. The ongoing vaccination programs can slow down the spread of the virus; however, from time to time, the newly emerging variants of concern and antivaccination movements carry the possibility for the disease to remain in our daily lives. After the appearance of SARS-CoV-2, there was scholarly debate whether the virus was of natural origin, or it emerged from a laboratory, some even thinking the agent's potential biological weapon properties suggest the latter scenario. Later, the bioweapon theory was dismissed by the majority of experts, but the question remains that despite its natural origin, how potent a biological weapon the SARS-CoV-2 virus can become over time. MATERIALS AND METHODS: Based on 12 bioweapon threat assessment criteria already published in 2018, we performed a literature search and review, focusing on relevant potential bioweapon properties of the virus SARS-CoV-2. Instead of utilizing a survey among experts, we tried to qualify and quantify characteristics according to the available data found in peer-reviewed papers. We also identified other key elements not mentioned in the original 12 bioweapon criteria, which can play an important role in assessing future biological weapons. RESULTS: According to the international literature we analyzed, SARS-CoV-2 is a moderately infectious agent (ID50 estimated between 100 and 1,000), with high infection-to-disease ratio (35%-45% rate of asymptomatic infected) and medium incubation period (1-34 days, mean 6-7 days). Its morbidity and mortality rate can be categorized as medium (high morbidity rate with significant mortality rate). It can be easily produced in large quantities, has high aerosol stability, and has moderate environmental stability. Based on laboratory experiments and statistical model analysis, it can form and is contagious with droplet nuclei, and with spray technique utilization, it could be weaponized effectively. Several prophylactic countermeasures are available in the form of vaccines; however, specific therapeutic options are much more limited. In connection with the original assessment criteria, the SARS-CoV-2 only achieved a "0" score on the ease of detection because of readily available, relatively sensitive, and specific rapid antigen tests. Based on the pandemic experience, we also propose three new assessment categories: one that establishes a mean to measure the necessary quarantine restrictions related to a biological agent, another one that can represent the personal protective equipment required to work safely with a particular agent, and a third one that quantifies the overall disruptive capability, based on previous real-life experiences. These factors could further specify the threat level related to potential biological weapons. CONCLUSIONS: Our results show that the virus can become a potent bioweapon candidate in the future, achieving a total score of 24 out of 36 on the original 12 criteria. The SARS-CoV-2 has already proven its pandemic generating potential and, despite worldwide efforts, still remains an imminent threat. In order to be prepared for the future possibility of the virus arising as a bioweapon, we must remain cautious and take the necessary countermeasures.

Multiple SARS-CoV-2 Introductions Shaped the Early Outbreak in Central Eastern Europe: Comparing Hungarian Data to a Worldwide Sequence Data-Matrix.

Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019, the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of 21 April 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here, we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.

Changes in patterns of injecting drug use in Hungary: a shift to synthetic cathinones.

The spread of synthetic cathinone injecting is a new phenomenon observed in recent years in Hungary. Until 2010, when the first anecdotal reports on cathinone injecting appeared, injecting was associated with the use of heroin and amphetamine. In this paper we review available evidence of the changes in the drug market and a concurrent shift in patterns of injecting drug use that have been taking place in Hungary since 2010. Remarkable changes have been observed in police seizures data since 2010. While new psychoactive substances have appeared, the availability of heroin has dropped significantly. A qualitative study in 2011 revealed that these market changes correlate with changes in patterns of injecting drug use: decreasing heroin use and the appearance of mephedrone injecting were reported by treatment and needle and syringe programme (NSP) personnel. These changes are detectable in other routine epidemiological data collection systems in the following years as well (i.e. treatment, drug-related deaths, NSP clientele). Heroin-related treatment demand dropped, as did heroin-related mortality. Parallel to this, a growing number of clients appeared in treatment and in NSPs who were primarily injecting cathinones. The shift to cathinones can be observed in amphetamine and heroin injectors as well. Monitoring changes in patterns of injecting drug use are especially important because of the vulnerability of this drug-user population and the consequences of this high-risk route of drug administration. The realignment observed in Hungary is to be further investigated with regard to its determinants, changes in risk behaviour, and in treatment needs.