Rapidly prototyped multi-scale electrodes to minimize the voltage requirements for bacterial cell lysis.

Lab-on-a-chip systems used for nucleic acid based detection of bacteria rely on bacterial lysis for the release of cellular material. Although electrical lysis devices can be miniaturized for on-chip integration and reagent-free lysis, they often suffer from high voltage requirements, and rely on the use of off-chip voltage supplies. To overcome this barrier, we developed a rapid prototyping method for creating multi-scale electrodes that are structurally tuned for lowering the voltage needed for electrical bacterial lysis. These three-dimensional multi-scale electrodes ­ with micron scale reaction areas and nanoscale features ­ are fabricated using benchtop methods including craft cutting, polymer-induced wrinkling, and electrodeposition, which enable a lysis device to be designed, fabricated, and optimized in a matter of hours. These tunable electrodes show superior behaviour compared to lithographically-prepared electrodes in terms of lysis efficiency and voltage requirement. Successful extraction of nucleic acids from bacterial samples processed by these electrodes demonstrates the potential for these rapidly prototyped devices to be integrated within practical lab-on-a-chip systems.

Exploring Perceptions of Competency-Based Medical Education in Undergraduate Medical Students and Faculty: A Program Evaluation.

Background: There is limited work exploring competency-based medical education (CBME) in undergraduate medical education. We aimed to assess medical students' and faculty's perception of CBME in the undergraduate medicine setting after its implementation at our institution through a Content, Input, Process, Product (CIPP) program evaluation model. Methods: We explored the rationale for the transition to a CBME curriculum (Content), the changes to the curriculum and the teams involved in the transition (Input), medical students' and faculty's perception of the current CBME curriculum (Process), and benefits and challenges of implementing undergraduate CBME (Product). A cross-sectional online survey was delivered over 8-weeks in October 2021 to medical students and faculty as part of the Process and Product evaluation. Results: Medical students displayed greater optimism towards CBME, compared to faculty, in terms of its role in medical education (p<0.05). Faculty were less certain about how CBME was currently implemented (p<0.05), as well as how feedback to students should be delivered (p<0.05). Students and faculty agreed on perceived benefits to CBME implementation. Faculty time commitment to teaching and logistical concerns were reported as perceived challenges. Conclusion: Education leaders must prioritize faculty engagement and continued professional development of faculty to facilitate the transition. This program evaluation identified strategies to aid the transition to CBME in the undergraduate setting.

Corrigendum: New perspectives on an old grouping: the genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.

[This corrects the article DOI: 10.3389/fmicb.2022.1011102.].

Carbon monoxide mechanism of protection against renal ischemia and reperfusion injury.

Carbon monoxide is quickly moving past its historic label as a molecule once feared, to a therapeutic drug that modulates inflammation. The development of carbon monoxide releasing molecules and utilization of heme oxygenase-1 inducers have shown carbon monoxide to be a promising therapy in reducing renal ischemia and reperfusion injury and other inflammatory diseases. In this review, we will discuss the developments and application of carbon monoxide releasing molecules in renal ischemia and reperfusion injury, and transplantation. We will review the anti-inflammatory mechanisms of carbon monoxide in respect to mitigating apoptosis, suppressing dendritic cell maturation and signalling, inhibiting toll-like receptor activation, promoting anti-inflammatory responses, and the effects on renal vasculature.

Incidence of interruptive penicillin allergy alerts in patients with previously documented beta-lactam exposure: Potential for leveraging the electronic health record to identify erroneous allergies.

BACKGROUND: Approximately 10% of patients report allergies to penicillin, yet >90% of these allergies are not clinically significant. Patients reporting penicillin allergies are often treated with second-line, non-ß-lactam antibiotics that are typically broader spectrum and more toxic. Orders for ß-lactam antibiotics for these patients trigger interruptive alerts, even when there is electronic health record (EHR) data indicating prior ß-lactam exposure. OBJECTIVE: To describe the rate that interruptive penicillin allergy alerts display for patients who have previously had a ß-lactam exposure. DESIGN: Retrospective EHR review from January 2013 through June 2018. SETTING: A nonprofit health system including 1 large tertiary-care medical center, a smaller associated hospital, 2 emergency departments, and ˜250 outpatient clinics. PARTICIPANTS: All patients with EHR-documented of penicillin allergies. METHODS: We examined interruptive penicillin allergy alerts and identified the number and percentage of alerts that display for patients with a prior administration of a penicillin class or other ß-lactam antibiotic. RESULTS: Of 115,081 allergy alerts that displayed during the study period, 8% were displayed for patients who had an inpatient administration of a penicillin antibiotic after the allergy was noted, and 49% were displayed for patients with a prior inpatient administration of any ß-lactam. CONCLUSIONS: Many interruptive penicillin allergy alerts display for patients who would likely tolerate a penicillin, and half of all alerts display for patients who would likely tolerate another ß-lactam.

New perspectives on an old grouping: The genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.

Oxalobacter formigenes is a unique bacterium with the ability to metabolize oxalate as a primary carbon source. Most kidney stones in humans are composed of calcium and oxalate. Therefore, supplementation with an oxalate-degrading bacterium may reduce stone burden in patients suffering from recurrent calcium oxalate-based urolithiasis. Strains of O. formigenes are divided into two groups: group I and group II. However, the differences between strains from each group remain unclear and elucidating these distinctions will provide a better understanding of their physiology and potential clinical applications. Here, genomes from multiple O. formigenes strains underwent whole genome sequencing followed by phylogenetic and functional analyses. Genetic differences suggest that the O. formigenes taxon should be divided into an additional three species: Oxalobacter aliiformigenes sp. nov, Oxalobacter paeniformigenes sp. nov, and Oxalobacter paraformigenes sp. nov. Despite the similarities in the oxalyl-CoA gene (oxc), which is essential for oxalate degradation, these strains have multiple unique genetic features that may be potential exploited for clinical use. Further investigation into the growth of these strains in a simulated fecal environment revealed that O. aliiformigenes strains are capable of thriving within the human gut microbiota. O. aliiformigenes may be a better therapeutic candidate than current group I strains (retaining the name O. formigenes), which have been previously tested and shown to be ineffective as an oral supplement to mitigate stone disease. By performing genomic analyses and identifying these novel characteristics, Oxalobacter strains better suited to mitigation of calcium oxalate-based urolithiasis may be identified in the future.

Techno-economic analysis of a transient plant-based platform for monoclonal antibody production.

Plant-based biomanufacturing of therapeutic proteins is a relatively new platform with a small number of commercial-scale facilities, but offers advantages of linear scalability, reduced upstream complexity, reduced time to market, and potentially lower capital and operating costs. In this study we present a detailed process simulation model for a large-scale new "greenfield" biomanufacturing facility that uses transient agroinfiltration of Nicotiana benthamiana plants grown hydroponically indoors under light-emitting diode lighting for the production of a monoclonal antibody. The model was used to evaluate the total capital investment, annual operating cost, and cost of goods sold as a function of mAb expression level in the plant (g mAb/kg fresh weight of the plant) and production capacity (kg mAb/year). For the Base Case design scenario (300 kg mAb/year, 1 g mAb/kg fresh weight, and 65% recovery in downstream processing), the model predicts a total capital investment of $122 million dollars and cost of goods sold of $121/g including depreciation. Compared with traditional biomanufacturing platforms that use mammalian cells grown in bioreactors, the model predicts significant reductions in capital investment and >50% reduction in cost of goods compared with published values at similar production scales. The simulation model can be modified or adapted by others to assess the profitability of alternative designs, implement different process assumptions, and help guide process development and optimization.