Developing a Graduate Class on Synthetic Cells at a Minority Serving Institution: Lessons from the University of New Mexico.

This article describes the development, methodology, enrollment, and outcomes of a graduate technical elective course on synthetic cells and organelles offered at the University of New Mexico, a minority-majority institution, in Fall 2022. The course had a significant ethics component and took advantage of readily available, low cost, and no-cost teaching materials that are available online. The course was effective in attracting a diverse enrollment of graduate students and senior undergraduates, some of whom participated in a survey of their backgrounds and motivations after the course was over. The article also provides results from this survey. Courses such as the one described have the potential to increase access and participation in emerging fields of research and technology such as synthetic cells.

Oral Valacyclovir Treatment of Herpes Zoster Ophthalmicus-Induced Optic Neuritis.

Herpes zoster ophthalmicus (HZO) rarely manifests with complications of the optic nerve. The traditional standard of care for sight-threatening HZO infection involves intravenous hospital administration of the antiviral medication acyclovir. This case report entails an HZO complication invading the optic nerve, effectively treated by oral administration of the antiviral medication valacyclovir in an immunocompetent patient. Intravenous administration of antiviral medication may be undesirable for some patients with HZO due to comparative cost, stronger associations to nephrotoxicity, increased dosing frequency, and the need for hospitalization. Oral antiviral tablets have an efficacious route of administration to be considered over intravenous hospital administration when devising treatment for HZO with the rare complication of optic neuritis in immunocompetent patients.

Woven Stainless-Steel Mesh as a Gas Separation Membrane for Alkaline Water-Splitting Electrolysis.

A 316-grade woven stainless-steel mesh membrane was investigated as a gas-separation membrane for alkaline water-splitting electrolysis. Its resistance was measured using electrochemical impedance spectroscopy (EIS) and linear sweep voltammetry (LSV), with the conclusion that it presented approximately half the resistance of a comparable commercial alternative (ZirfonTM). Its gas-separation performance was analysed using gas chromatography (GC) at 140 mA cm-2, where it achieved 99.25% purity at the hydrogen outlet of the electrolyser. This fell to 97.5% under pumped circulation, which highlights that it is sensitive to pressure differentials. Nevertheless, this mixture is still more than a factor two inside the upper flammability limit of hydrogen in oxygen. It is hoped that such a low-cost material may bring entry-level electrolysis to many hitherto discounted applications.

Photocapacitive CdS/WOx nanostructures for solar energy storage.

Through a facile solvothermal procedure, a CdS/WOx nanocomposite has been synthesised which exhibits photocapacitive behaviour under white light illumination at a radiant flux density of 99.3 mW cm-2. Photoelectrochemical experiments were undertaken to examine the self-charging properties of the material and to develop an understanding of the underlying electronic band structure responsible for the phenomenon. By employing XPS, UPS and UV-Vis diffuse reflectance spectroscopy for further characterisation, the ability of the composite to generate current following the removal of incident light was related to the trapping of photoexcited electrons by the WOx component. The presence of WOx yielded an order of magnitude increase in the transient photocurrent response relative to CdS alone, an effect attributed to the suppression of electron-hole recombination in CdS due to hole transfer across the CdS/WOx interface. Moreover, current discharge from the material persisted for more than twenty minutes after final illumination, an order of magnitude improvement over many existing binary composites. As a seminal investigation into the photocapacitive characteristics of CdS/WOx composites, the work offers insight into how the constituent materials might be utilised as part of a future self-charging solar device.

Victor Frankenstein's Institutional Review Board Proposal, 1790.

To show how the case of Mary Shelley's Victor Frankenstein brings light to the ethical and moral issues raised in Institutional Review Board (IRB) protocols, we nest an imaginary IRB proposal dated August 1790 by Victor Frankenstein within a discussion of the importance and function of the IRB. Considering the world of science as would have appeared in 1790 when Victor was a student at Ingolstadt, we offer a schematic overview of a fecund moment when advances in comparative anatomy, medical experimentation and theories of life involving animalcules and animal electricity sparked intensive debates about the basic principles of life and the relationship between body and soul. Constructing an IRB application based upon myriad speculations circulating up to 1790, we imagine how Victor would have drawn upon his contemporaries' scientific work to justify the feasibility of his project, as well as how he might have outlined the ethical implications of his plan to animate life from "dead" tissues. In Mary Shelley's Frankenstein, Victor failed to consider his creature's autonomy, vulnerability, and welfare. In this IRB proposal, we show Victor facing those issues of justice and emphasize how the novel can be an important component in courses or workshops on research ethics. Had Victor Frankenstein had to submit an IRB proposal tragedy may have been averted, for he would have been compelled to consider the consequences of his experiment and acknowledge, if not fulfill, his concomitant responsibilities to the creature that he abandoned and left to fend for itself.

PRTX-100 and methotrexate in patients with active rheumatoid arthritis: A Phase Ib randomized, double-blind, placebo-controlled, dose-escalation study.

PRTX-100 is a highly-purified preparation of staphylococcal protein A (SpA), with immunologic activity in vitro and in animal models of immune-mediated inflammation. Following single-dose healthy volunteer studies of safety and pharmacokinetics (PK), a multicenter, double-blind, placebo-controlled, sequential dose-escalation, repeated-dose phase I trial was conducted in patients with active rheumatoid arthritis (RA) on methotrexate therapy. Patients were randomized to receive either weekly intravenous PRTX-100 (0.15, 0.45, 0.90, or 1.50 µg/kg) or placebo for 4 weeks. Safety and disease activity were assessed over 16 weeks. Pharmacokinetic profiles were obtained after the first and fourth doses. The most common treatment-related adverse events were nausea, muscle spasms, dizziness, flushing, fatigue, RA flare, and headache. No serious adverse events were considered related to PRTX-100, and none occurred in the highest dose group. Geometric mean values for plasma Cmax (ng/mL) were 4.1, 15.7, 26.5, and 51.2 for doses of 0.15, 0.45, 0.90, and 1.5 µg/kg, respectively. Anti-drug antibodies (ADAs) developed in most PRTX-100 patients, but incidence and titer were not dose-dependent. At the two highest doses, data suggest PRTX-100 may have an effect on RA disease activity, even in patients with ADAs.

Craniofacial dysmorphism and developmental disorders among children with chromosomal microdeletions and duplications of unknown significance.

OBJECTIVE: Microarray comparative genomic hybridization is an extremely sensitive technology that increasingly identifies deletions and duplications of unknown significance. Our objective was to determine whether children with autism and other developmental delays who have genomic imbalances manifest more craniofacial dysmorphism and have lower cognitive scores than children from the same clinic population who have normal microarrays. METHOD: A clinical geneticist, blinded to the history, reviewed photographs for craniofacial dysmorphism. Forty-five (24%) of 187 children who had a microarray had a deletion or duplication >200 kb. Thirty-six of those with abnormal microarrays (11 microdeletions and 25 duplications) had completed their evaluation, which included 3 deletions and 10 duplications of unknown significance. Subjects with and without microarray anomalies did not differ in age, sex, growth parameters, parental age or education level, insurance status, or cognitive scores. RESULTS: Twenty-eight (78%) of the 36 children with microarray anomalies had craniofacial dysmorphism as compared with 45% of those with normal microarrays (p = .0005). Among the 13 children with microarray abnormalities of unknown significance, 10 (77%) were dysmorphic, similar to 18 (78%) of 23 who had a genomic imbalance known to affect development. Among the 10 children with dysmorphism and a microarray anomaly of unknown significance, 7 also had an IQ ≤70 and/or a diagnosis of autism. CONCLUSION: Microdeletions and duplications not previously known to be associated with human disease were strongly associated with craniofacial dysmorphism, cognitive scores ≤70, and a diagnosis of autism in this clinic population, providing presumptive evidence that these genomic imbalances are clinically significant.

Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine.

PURPOSE: A novel nanomedicine, CYT-6091, constructed by simultaneously binding recombinant human tumor necrosis factor alpha (rhTNF) and thiolyated polyethylene glycol to the surface of 27-nm colloidal gold particles, was tested in a phase I dose escalation clinical trial in advanced stage cancer patients. EXPERIMENTAL DESIGN: CYT-6091, whose dosing was based on the amount of rhTNF in the nanomedicine, was injected intravenously, and 1 cycle of treatment consisted of 2 treatments administered 14 days apart. RESULTS: Doses from 50 µg/m(2) to 600 µg/m(2) were well tolerated, and no maximum tolerated dose (MTD) was reached, as the highest dose exceeded the target dosage of 1-mg rhTNF per treatment, exceeding the previous MTD for native rhTNF by 3-fold. The first 2 patients on the study, each receiving 50 µg/m(2), did not receive any prophylactic antipyretics or H2 blockade. A predicted, yet controllable fever occurred in these patients, so all subsequently treated patients received prophylactic antipyretics and H2 blockers. However, even at the highest dose rhTNF's dose-limiting toxic effect of hypotension was not seen. Using electron microscopy to visualize nanoparticles of gold in patient biopsies of tumor and healthy tissue showed that patient biopsies taken 24 hours after treatment had nanoparticles of gold in tumor tissue. CONCLUSIONS: These data indicate that rhTNF formulated as CYT-6091 may be administered systemically at doses of rhTNF that were previously shown to be toxic and that CYT-6091 may target to tumors. Future clinical studies will focus on combining CYT-6091 with approved chemotherapies for the systemic treatment of nonresectable cancers.

Establishing quality assurance criteria for serial dilution operations on liquid-handling equipment.

Since the advent of high-throughput screening (HTS) in the early 1990s, parallel multichannel liquid handlers have become a mainstay in every drug discovery setting. Although several peer-reviewed publications have discussed methods and criteria for stamping multiwell copies, there is very little information about establishing a standard operating procedure (SOP) for standard (microliter-level) serial dilutions of compounds used in dose-response experiments. The authors discuss the 4 main criteria any serial dilution process must pass (accuracy, precision, fold dilution, and outliers) and the process for establishing thresholds for all of these values in a compound management or biological screening laboratory. The thresholds need to be both low enough to be acceptable from a biological potency variability perspective and high enough to allow the instruments to pass the quality assurance (QA) analysis on a regular basis. In this article, the authors suggest suitable thresholds arrived at by a variety of methods, including trend analysis of QA data, survey questionnaire from the main stakeholders (screening scientists, chemists), and published criteria for single-shot stamping. A mathematical analysis of the effect of threshold values on estimated XC(50)s was performed to ensure that the variability introduced by the serial dilution step is within acceptable overall variability limits.

Speaking the right language: the scientific method as a framework for a continuous quality improvement program within academic medical research compliance units.

The authors developed a novel continuous quality improvement (CQI) process for academic biomedical research compliance administration. A challenge in developing a quality improvement program in a nonbusiness environment is that the terminology and processes are often foreign. Rather than training staff in an existing quality improvement process, the authors opted to develop a novel process based on the scientific method--a paradigm familiar to all team members. The CQI process included our research compliance units. Unit leaders identified problems in compliance administration where a resolution would have a positive impact and which could be resolved or improved with current resources. They then generated testable hypotheses about a change to standard practice expected to improve the problem, and they developed methods and metrics to assess the impact of the change. The CQI process was managed in a "peer review" environment. The program included processes to reduce the incidence of infections in animal colonies, decrease research protocol-approval times, improve compliance and protection of animal and human research subjects, and improve research protocol quality. This novel CQI approach is well suited to the needs and the unique processes of research compliance administration. Using the scientific method as the improvement paradigm fostered acceptance of the project by unit leaders and facilitated the development of specific improvement projects. These quality initiatives will allow us to improve support for investigators while ensuring that compliance standards continue to be met. We believe that our CQI process can readily be used in other academically based offices of research.