Does a large prostate size, small lesion volume, or long needle distance from the probe to the lesion reduce magnetic resonance imaging-targeted cancer detection?

Background: We aimed to evaluate whether large prostate size, small lesion volume, or long lesion distance from the ultrasound probe tip would decrease cancer detection in transrectal magnetic resonance imaging (MRI)-targeted biopsies. Materials and methods: Patients who underwent MRI-targeted biopsy at our institution between May 2017 and August 2019 were enrolled in a prospective database. Three to 5 cores were obtained from ≥2 prostate imaging reporting and data system v2 lesions. A multivariable model was created that included needle distance to the lesion, prostate specific antigen, prostate imaging reporting and data system, lesion volume, and prostate volume. Results: A total of 377 patients with 533 lesions underwent a biopsy during the study period. A total of 233 (44%) lesions were positive for prostate cancer, and 173 (32%) lesions had clinically significant prostate cancer. The mean needle distance to the lesion was 11.7 mm (interquartile range, 7.6-15.5 mm). The likelihood of obtaining a positive core on biopsy decreased as the distance from the ultrasound probe increased for all prostate cancers and clinically significant prostate cancer (p = 0.018 and p = 0.004, respectively). Every 10 mm from the rectum, there was an 8%-10% decrease in the rate of cancer detection. Similarly, as the prostate volume increased, the odds of obtaining a positive core also decreased (p = 0.039). There was no significant association between the lesion size and amount of cancer obtained on biopsy. Conclusions: Our data showed that transrectal MRI-targeted biopsy cancer detection modestly decreased the lesion from the ultrasound probe and with a large prostate volume but could not prove that lesion volume was a significant predictor of the amount of cancer detected.

Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high-throughput assay for possible use in ecological hazard screening.

Transcriptomics-Based Points of Departure for Daphnia magna Exposed to 18 Per- and Polyfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFAS) represent a large group of contaminants of concern based on their widespread use, environmental persistence, and potential toxicity. Many traditional models for estimating toxicity, bioaccumulation, and other toxicological properties are not well suited for PFAS. Consequently, there is a need to generate hazard information for PFAS in an efficient and cost-effective manner. In the present study, Daphnia magna were exposed to multiple concentrations of 22 different PFAS for 24 h in a 96-well plate format. Following exposure, whole-body RNA was extracted and extracts, each representing five exposed individuals, were subjected to RNA sequencing. Following analytical measurements to verify PFAS exposure concentrations and quality control on processed cDNA libraries for sequencing, concentration-response modeling was applied to the data sets for 18 of the tested compounds, and the concentration at which a concerted molecular response occurred (transcriptomic point of departure; tPOD) was calculated. The tPODs, based on measured concentrations of PFAS, generally ranged from 0.03 to 0.58 µM (9.9-350 µg/L; interquartile range). In most cases, these concentrations were two orders of magnitude lower than similarly calculated tPODs for human cell lines exposed to PFAS. They were also lower than apical effect concentrations reported for seven PFAS for which some crustacean or invertebrate toxicity data were available, although there were a few exceptions. Despite being lower than most other available hazard benchmarks, D. magna tPODs were, on average, four orders of magnitude greater than the maximum aqueous concentrations of PFAS measured in Great Lakes tributaries. Overall, this high-throughput transcriptomics assay with D. magna holds promise as a component of a tiered hazard evaluation strategy employing new approach methodologies. Environ Toxicol Chem 2024;00:1-16. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Derivation of Transcriptomics-Based Points of Departure for 20 Per- or Polyfluoroalkyl Substances Using a Larval Fathead Minnow (Pimephales promelas) Reduced Transcriptome Assay.

Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that ecological hazards of most PFAS remain uncharacterized. The present study employed a high-throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response (termed a transcriptomics-based point of departure [tPOD]) in larval fathead minnows (Pimephales promelas; 5-6 days postfertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole-body expression of 1832 genes, the median tPOD for the 20 PFAS tested was 10 µM. Longer-chain carboxylic acids (12-13 C-F); an eight-C-F dialcohol, N-alkyl sulfonamide; and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations <1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole-transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sublethal effects have been reported in fish (available for 10 PFAS). Nonetheless, fathead minnow tPODs were orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes, suggesting a substantial margin of safety. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening-level potency estimates for use in ecological risk-based prioritization. Environ Toxicol Chem 2024;00:1-16. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.