Magnetic Stimulation Allows Focal Activation of the Mouse Cochlea

Cochlear implants (CIs) strive to restore hearing to those with severe to profound hearing loss by artificially stimulating the auditory nerve. While most CI users can understand speech in a quiet environment, hearing that utilizes complex neural coding (e.g., appreciating music) has proved elusive, probably because of the inability of CIs to create narrow regions of spectral activation. Several novel approaches have recently shown promise for improving spatial selectivity, but substantial design differences from conventional CIs will necessitate much additional safety testing before clinical viability is established. Outside the cochlea, magnetic stimulation from small coils (micro-coils) has been shown to confine activation more narrowly than that from conventional micro-electrodes, raising the possibility that coil-based stimulation of the cochlea could improve the spectral resolution of CIs. To explore this, we delivered magnetic stimulation from micro-coils to multiple locations of the cochlea and measured the spread of activation utilizing a multi-electrode array inserted into the inferior colliculus; responses to magnetic stimulation were compared to analogous experiments with conventional micro-electrodes as well as to the responses to auditory monotones. Encouragingly, the extent of activation with micro-coils was ~60% narrower than that from electric stimulation and largely similar to the spread arising from acoustic stimulation. The dynamic range of coils was more than three times larger than that of electrodes, further supporting a smaller spread of activation. While much additional testing is required, these results support the notion that coil-based CIs can produce a larger number of independent spectral channels and may therefore improve functional performance. Further, because coil-based devices are structurally similar to existing CIs, fewer impediments to clinical translational are likely to arise.

Human Factors and Ergonomics in Healthcare: Industry Demands and a Path Forward

This article reviews three industry demands that will impact the future of Human Factors and Ergonomics in Healthcare settings. These demands include the growing population of older adults, the increasing use of telemedicine, and a focus on patient-centered care. Following, we discuss a path forward through improved medical teams, error management, and safety testing of medical devices and tools. Future challenges are discussed.

Artificial intelligence unifies knowledge and actions in drug repositioning

Drug repositioning aims to reuse existing drugs, shelved drugs, or drug candidates that failed clinical trials for other medical indications. Its attraction is sprung from the reduction in risk associated with safety testing of new medications and the time to get a known drug into the clinics. Artificial Intelligence (AI) has been recently pursued to speed up drug repositioning and discovery. The essence of AI in drug repositioning is to unify the knowledge and actions, i.e. incorporating real-world and experimental data to map out the best way forward to identify effective therapeutics against a disease. In this review, we share positive expectations for the evolution of AI and drug repositioning and summarize the role of AI in several methods of drug repositioning.

An Immunocompetent Microphysiological System to Simultaneously Investigate Effects of Anti-Tumor Natural Killer Cells on Tumor and Cardiac Microtissues

Existing first-line cancer therapies often fail to cope with the heterogeneity and complexity of cancers, so that new therapeutic approaches are urgently needed. Among novel alternative therapies, adoptive cell therapy (ACT) has emerged as a promising cancer treatment in recent years. The limited clinical applications of ACT, despite its advantages over standard-of-care therapies, can be attributed to (i) time-consuming and cost-intensive procedures to screen for potent anti-tumor immune cells and the corresponding targets, (ii) difficulties to translate in-vitro and animal-derived in-vivo efficacies to clinical efficacy in humans, and (iii) the lack of systemic methods for the safety assessment of ACT. Suitable experimental models and testing platforms have the potential to accelerate the development of ACT. Immunocompetent microphysiological systems (iMPS) are microfluidic platforms that enable complex interactions of advanced tissue models with different immune cell types, bridging the gap between in-vitro and in-vivo studies. Here, we present a proof-of-concept iMPS that supports a triple culture of three-dimensional (3D) colorectal tumor microtissues, 3D cardiac microtissues, and human-derived natural killer (NK) cells in the same microfluidic network. Different aspects of tumor-NK cell interactions were characterized using this iMPS including: (i) direct interaction and NK cell-mediated tumor killing, (ii) the development of an inflammatory milieu through enrichment of soluble pro-inflammatory chemokines and cytokines, and (iii) secondary effects on healthy cardiac microtissues. We found a specific NK cell-mediated tumor-killing activity and elevated levels of tumor- and NK cell-derived chemokines and cytokines, indicating crosstalk and development of an inflammatory milieu. While viability and morphological integrity of cardiac microtissues remained mostly unaffected, we were able to detect alterations in their beating behavior, which shows the potential of iMPS for both, efficacy and early safety testing of new candidate ACTs.

Whole-Genome Sequence Datasets: A Powerful Resource for the Food Microbiology Laboratory Toolbox

Whole-genome sequencing (WGS) technologies are rapidly being adopted for routine use in food microbiology laboratories worldwide. Examples of how WGS is used to support food safety testing include gene marker discovery (e.g., virulence and anti-microbial resistance gene determination) and high-resolution typing (e.g., cg/wgMLST analysis). This has led to the establishment of large WGS databases representing the genomes of thousands of different types of food pathogenic and commensal bacteria. This information constitutes an invaluable resource that can be leveraged to develop and validate routine test methods used to support regulatory and industry food safety objectives. For example, well-curated raw and assembled genomic datasets of the key food pathogens (Salmonella enterica, Listeria monocytogenes, and Shiga-toxigenic Escherichia coli) have been used in our laboratory in studies to validate bioinformatics pipelines, as well as new molecular methods as a prelude to the laboratory phase of the “wet lab” validation process. The application of genomic information to food microbiology method development will decrease the cost of test development and lead to the generation of more robust methodologies supporting risk assessment and risk management actions.

Carcinogenicity Evaluation of Baclofen in TgrasH2 Mice

Baclofen is a γ-aminobutyric acid-B receptor agonist used for control of spastic muscle activity and as a treatment for alcohol abuse. The review of the nonclinical database suggested a data gap for potential carcinogenicity following long-term use. Regulatory requirements for pharmaceutical safety testing of cancer-causing potential have historically included 2-year rodent studies in rats and mice. The availability of transgenic models with greater specificity and sensitivity to carcinogens provides safety testing alternatives that align with the 3Rs. The carcinogenicity of baclofen was evaluated in CB6F1-TgrasH2 transgenic mice following daily oral administration at 45, 90, and 180 mg/kg/d for 26 weeks, preceded by a 2-week drug-conditioning period. There were no treatment-related palpable masses or neoplastic findings, and survival rates were not affected by the baclofen treatment. In conclusion, baclofen was considered as noncarcinogenic in CB6F1-TgrasH2 mice, which is consistent with results previously obtained in a 2-year rat study.

Applications of THz Spectral Imaging in the Detection of Agricultural Products

Agricultural products need to be inspected for quality and safety, and the issue of safety of agricultural products caused by quality is frequently investigated. Safety testing should be carried out before agricultural products are consumed. The existing technologies for inspecting agricultural products are time-consuming and require complex operation, and there is motivation to develop a rapid, safe, and non-destructive inspection technology. In recent years, with the continuous progress of THz technology, THz spectral imaging, with the advantages of its unique characteristics, such as low energies, superior spatial resolution, and high sensitivity to water, has been recognized as an efficient and feasible identification tool, which has been widely used for the qualitative and quantitative analyses of agricultural production. In this paper, the current main performance achievements of the use of THz images are presented. In addition, recent advances in the application of THz spectral imaging technology for inspection of agricultural products are reviewed, including internal component detection, seed classification, pesticide residues detection, and foreign body and packaging inspection. Furthermore, machine learning methods applied in THz spectral imaging are discussed. Finally, the existing problems of THz spectral imaging technology are analyzed, and future research directions for THz spectral imaging technology are proposed. Recent rapid development of THz spectral imaging has demonstrated the advantages of THz radiation and its potential application in agricultural products. The rapid development of THz spectroscopic imaging combined with deep learning can be expected to have great potential for widespread application in the fields of agriculture and food engineering.

Improvement of the Thermocouple Method for Testing Energy-Intensive Emulsions for Compatibility with the Sulfide Ores

The results are presented concerning improving the thermostatic method for studying the chemical compatibility of modern industrial emulsion explosives based on the ammonium nitrate with surrounding materials, the increased reactivity of which can lead to spontaneous ignition and even explosion. An assessment of the compatibility of emulsion explosives with sulphide ores was conducted using an original thermocouple methodology developed at the D. Mendeleyev University of Chemical Technology of Russia, fixation of the thermal effects of the interaction of shell-free explosives based on the ammonium nitrate with sulfide minerals. Improved thermocouple method allows to determine chemical compatibility of the industrial explosives with the reactive rocks. It is distinguished by the possibility of continuous recording of the thermocouple measurements during tests using an oscilloscope and combines the reliability of the results with small laboratory weights of the test samples (no more than 20 g, which ensures safety testing). Temperature measurement accuracy is ± 2 °С. It is concluded that the method used is able to identify the cases of the most dangerous interaction from the practice point of view using the emulsion explosives when the pyrite content in the ore exceeds 85 %. The results of experiments on the applicability of thermocouple measurements to testing low-activity rocks, highly reactive pyrite ores, mixed sulfide ores of medium activity, as well as on the identification of the main regularities of heat release during the interaction of emulsion explosives with the sulfide ores are considered.