Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

Running the gauntlet; flyway-wide patterns of pollutant exposure in blood of migratory shorebirds.

Shorebirds (order Charadriiformes) are among the world's most threatened avian taxa. Within the East Asian-Australasian Flyway (EAAF), a major threat to shorebirds' survival may be the gauntlet of pollution along the flyway. Metals, persistent organic pollutants (POPs), and per-/polyfluoroalkyl substances (PFASs) persist in the environment to the detriment of wildlife. In this study, we analysed element and PFAS concentrations in blood from 142 individuals across six species of Arctic-breeding migratory shorebirds with contrasting population trends, to discern species- and site-specific pollution differences, and determine how pollution correlated with population trends of EAAF shorebirds. Potential within-year pollution variations were investigated by blood-sampling birds at two sites, representing different points in the birds' annual migrations: staging in Taiwan on southward migrations and at non-breeding grounds in Western Australia (WA). Species' pollutant concentrations were compared to established population trends. Concentrations of potentially toxic elements were low in most individuals regardless of species. PFASs (range: <0.001-141 ng/g), Hg (<0.001-9910 ng/g) and Pb (<0.01-1210 ng/g) were higher in Taiwan than in WA (PFAS Taiwan median: 14.5 ng/g, WA median: 3.45 ng/g; Hg Taiwan: 338 ng/g, WA: 23.4 ng/g; Pb Taiwan: 36.8 ng/g, WA: 2.26 ng/g). Meanwhile As (range <0.001-8840 ng/g) and Se (290-47600 ng/g) were higher in WA than Taiwan (As Taiwan median: 500 ng/g, WA median: 1660 ng/g; Se Taiwan: 5490 ng/g, Se WA: 23700 ng/g). Nevertheless, pollutant concentrations in a subset of individuals may exceed sublethal effect thresholds (As, Se and PFASs). Finally, we found no consistent differences in pollution among species and demonstrated no correlation between pollution and population trends, suggesting pollution is likely not a major driver for population declines of EAAF shorebirds. However, ongoing and locally heavy environmental degradation and exposure to other contaminants not investigated here, such as POPs, warrants continued consideration when managing EAAF shorebird populations.

Feasibility of Using a Novel Drop-In Gamma Probe for 99mTc-PSMA-I&S-Guided Lymph Node Detection During Robot-Assisted Radical Prostatectomy for Primary Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) has gained increased interest in prostate cancer (PCa). This analysis aims to evaluate the feasibility, safety, and limitations of RGS with a novel drop-in gamma probe in primary PCa. PATIENTS AND METHODS: The data of 13 patients with primary PCa undergoing RGS were analyzed retrospectively. After preoperative administration of 99mTc-PSMA-I&S, a SPECT/CT was conducted and a robotic radical prostatectomy was performed the following day including intraoperative assessment of the lymph node stations using a novel robotic drop-in gamma probe. This was followed by an extended pelvic lymph node dissection (ePLND) with ex vivo control measurement using the drop-in and a conventional rigid gamma probe. RESULTS: Eleven patients (median PSA value of 11 ng/mL) had high-risk and 2 patients had intermediate-risk PCa. Overall, a median of 22 ePLND lymph nodes were dissected. In 1 patient, preoperative SPECT/CT imaging showed suspicious lymph nodes, which could be confirmed intraoperatively with the robotic drop-in probe and subsequently in the final histopathological analysis. RGS failed to identify 2 patients with micrometastases (<3 mm) preoperatively and intraoperatively. No postoperative complications related to 99mTc-PSMA-I&S RGS or ePLND occurred. CONCLUSIONS: RGS with the novel drop-in gamma probe and 99mTc-PSMA-I&S allows for a reliable intraoperative screening for lymph node metastases in robot-assisted radical prostatectomy for primary PCa with an acceptable safety profile. However, limitations in the detection of micrometastases need to be overcome before omitting extended ePLND in patients at risk for lymphatic spread.

Toward Quantitative Multisite Preclinical Imaging Studies in Acute Myocardial Infarction: Evaluation of the Immune-Fibrosis Axis.

The immune-fibrosis axis plays a critical role in cardiac remodeling after acute myocardial infarction. Imaging approaches to monitor temporal inflammation and fibroblast activation in mice have seen wide application in recent years. However, the repeatability of quantitative measurements remains challenging, particularly across multiple imaging centers. We aimed to determine reproducibility of quantitative inflammation and fibroblast activation images acquired at 2 facilities after myocardial infarction in mice. Methods: Mice underwent coronary artery ligation and sequential imaging with 68Ga-DOTA-ECL1i to assess chemokine receptor type 2 expression at 3 d after myocardial infarction and 68Ga-FAPI-46 to assess fibroblast activation protein expression at 7 d after myocardial infarction. Images were acquired at 1 center using either a local or a consensus protocol developed with the second center; the protocols differed in the duration of isoflurane anesthesia and the injected tracer dose. A second group of animals were scanned at the second site using the consensus protocol. Image analyses performed by each site and just by 1 site were also compared. Results: The uptake of 68Ga-DOTA-ECL1i in the infarct territory tended to be higher when the consensus protocol was used (P = 0.03). No difference was observed between protocol acquisitions for 68Ga-FAPI-46. Compared with the local protocol, the consensus protocol decreased variability between individual animals. When a matched consensus protocol was used, the 68Ga-DOTA-ECL1i infarct territory percentage injected dose per gram of tissue was higher on images acquired at site B than on those acquired at site A (P = 0.006). When normalized to body weight as SUV, this difference was mitigated. Both the percentage injected dose per gram of tissue and the SUV were comparable between sites for 68Ga-FAPI-46. Image analyses at the sites differed significantly, but this difference was mitigated when all images were analyzed at site A. Conclusion: The application of a standardized acquisition protocol may lower variability within datasets and facilitate comparison of molecular radiotracer distribution between preclinical imaging centers. Like clinical studies, multicenter preclinical studies should use centralized core-based image analysis to maximize reproducibility across sites.

Correction: Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/44204.].