Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma.

Introduction: Integrated time nanosecond pulse irreversible electroporation (INSPIRE) is a novel tumor ablation modality that employs high voltage, alternating polarity waveforms to induce cell death in a well-defined volume while sparing the underlying tissue. This study aimed to demonstrate the in vivo efficacy of INSPIRE against spontaneous melanoma in standing, awake horses. Methods: A custom applicator and a pulse generation system were utilized in a pilot study to treat horses presenting with spontaneous melanoma. INSPIRE treatments were administered to 32 tumors across 6 horses and an additional 13 tumors were followed to act as untreated controls. Tumors were tracked over a 43-85 day period following a single INSPIRE treatment. Pulse widths of 500ns and 2000ns with voltages between 1000 V and 2000 V were investigated to determine the effect of these variables on treatment outcomes. Results: Treatments administered at the lowest voltage (1000 V) reduced tumor volumes by 11 to 15%. Higher voltage (2000 V) treatments reduced tumor volumes by 84 to 88% and eliminated 33% and 80% of tumors when 500 ns and 2000 ns pulses were administered, respectively. Discussion: Promising results were achieved without the use of chemotherapeutics, the use of general anesthesia, or the need for surgical resection in regions which are challenging to keep sterile. This novel therapeutic approach has the potential to expand the role of pulsed electric fields in veterinary patients, especially when general anesthesia is contraindicated, and warrants future studies to demonstrate the efficacy of INSPIRE as a solid tumor treatment.

Comparative Recovery of Serratia marcescens Using Bags versus Gloves as Described in ASTM E1174-21 Health Care Personnel Handwash Method.

The ASTM E1174-21 Health Care Personnel Handwash method is prescribed by the U.S. Food and Drug Administration (FDA) to demonstrate the efficacy of antiseptic handwashing products. The standardized method allows for marker bacteria to be collected from the hands by using either a bag or a glove. Two recent studies utilizing the different collection methods testing the same product showed substantial differences in results. We sponsored two independent studies to compare the bag and glove collection methods following contamination with Serratia marcescens. Overall, there was no difference between collection methods for bacteria recovered (P = 0.603). The distribution of recovery for the bag method was slightly less variable than for the glove method. Statistical differences were observed within each lab based on the collection day. The day-to-day variability is critical to consider for future multiple-day studies. Additionally, hand size appears to impact recovery, especially for the glove method, with both small and medium hand sizes resulting in higher recovery than large and extralarge hand sizes (P = 0.015), whereas hand size did not impact recovery with the bag method (P = 0.315). While it appears that both the bag and glove methods can be used, our findings suggest that gloves may not be the best option for subjects with large to extra-large hands. Additional work looking at bacterial recovery following product treatment is warranted to understand the impact of large hands in the bag versus glove recovery method. IMPORTANCE Antiseptic hand wash products are evaluated using the standard ASTM E1174-21 to demonstrate their antibacterial efficacy. Often products are tested at multiple labs, and the need to understand variables that may play a role in the outcome of the study is important. This work allows us to evaluate the impact that the two collection methods, bags and gloves, have on bacteria recovery. If differences are observed, standardization to one method may be critical to ensure similar test results when planning studies at multiple labs.

A brief, highly selective history of acute phase proteins as indicators of infection, inflammation and injury.

There is an array of plasma protein alterations that occur in a wide variety of species, including humans in response to trauma, inflammation and infections, seemingly irrespective of etiologic agent. In numerous species, these plasma proteins are part of the innate immune response. In addition, it appears that a number of the plasma proteins in this array can be predictive of morbidity and/or mortality. We propose that based on historic use, selected acute phase proteins should be included in ongoing and future non-clinical and clinical studies to help us better understand disease progression in chronic, as well as acute diseases. In addition to assess if there is a relationship between vaccine-induced inflammation and degree of protection from live, attenuated or synthetic vaccines.

How Much Nonclinical Safety Data Are Required for a Clinical Study in Ophthalmology?

Planning the nonclinical development program for an ophthalmic product requires first an understanding of how the drug will be used in the clinic-topical, injected, relatively short duration of testing, chronic testing, and what is already known about the drug. In some cases, when the drug is being repurposed or reformulated to allow for the same or different route of ocular administration, the requirements will be very different than for a first-in-class, novel drug. In general, ICH guidances have relatively little direction with respect to ophthalmology. Sponsors are encouraged to make use of meetings with the FDA, particularly for unusual situations, given this lack of specific ICH direction. In this article we describe the range of nonclinical studies required in our experience-pharmacology, pharmacokinetics and toxicology, with attention to the stage of clinical development and duration of treatment. As well, we discuss the coordination of effort with pharmaceutics researchers on drug substance and drug product.

Atmospheric Trace Molecule Spectroscopy (ATMOS) Experiment Version 3 data retrievals.

Version 3 of the Atmospheric Trace Molecule Spectroscopy (ATMOS) experiment data set for some 30 trace and minor gas profiles is available. From the IR solar-absorption spectra measured during four Space Shuttle missions (in 1985, 1992, 1993, and 1994), profiles from more than 350 occultations were retrieved from the upper troposphere to the lower mesosphere. Previous results were unreliable for tropospheric retrievals, but with a new global-fitting algorithm profiles are reliably returned down to altitudes as low as 6.5 km (clouds permitting) and include notably improved retrievals of H2O, CO, and other species. Results for stratospheric water are more consistent across the ATMOS spectral filters and do not indicate a net consumption of H2 in the upper stratosphere. A new sulfuric-acid aerosol product is described. An overview of ATMOS Version 3 processing is presented with a discussion of estimated uncertainties. Differences between these Version 3 and previously reported Version 2 ATMOS results are discussed. Retrievals are available at http://atmos.jpl.nasa.gov/atmos.