Exposure to noise or music in clinical trials: A scoping review on ethical and methodological considerations

Background: Use of noise or music in experimental human studies requires balancing the need to avoid subjecting participants to potentially harmful noise levels while still reaching levels that will produce a measurable change in the primary outcome. Several methodological and ethical aspects must be considered. This study aims to summarize ethical and methodological aspects, and reported outcomes, of previously published experimental paradigms using loud noise / music.Methods: and Materials: Four databases (Medline, Central, Web of Science and Scopus) and two trials registries (Clinicaltrials.gov, EU Clinical Trials) were searched. Extracted items were author and year of publication, study design and purpose, population, setting timeline and material, selected battery test, and effect of noise / music on participants’ hearing.Results: Thirty-four studies were included. Exposure safety considerations were reported in five studies. Eleven studies assessing hearing loss used white or narrow-band noise [(NBN(0.5-4 kHz), up to 115 dBA, duration range:3’-24 h)], and 10 used pop music (up to 106 dBA, duration range:10’-4 h). Experimental setting varied significantly. Temporary thresholds shift (TTS) and reduction in distortion product otoacoustic emissions were found at 1-8 kHz, with maximum average TTS~21.5 dB at 4 kHz after NBN and ~11.5 dB at 6 kHz after music exposure. All participants recovered their hearing, except for one participant in one study. In the 13 non-hearing loss studies, no hearing testing was performed after exposure, but loud noise was associated with temporary stress, bradygastria, 3 and cardiovascular changes. Noise-induced subjective stress may be higher for participants with tinnitus. Loud noise (100 dBA, 10’) increased diastolic and mean blood pressure only in participants with hypertension. Conclusions: Experimental exposure paradigms can produce temporary changes to hearing without measurable long-term health consequences. Methodological and ethical aspects identified in this review should be considered for the development of future paradigms. Keywor

Proteomic comparison between different tissue preservation methods for identification of promising biomarkers of urothelial bladder cancer

Samples in biobanks are generally preserved by formalin-fixation and paraffin-embedding (FFPE) and/or optimal cutting temperature compound (OCT)-embedding and subsequently frozen. Mass spectrometry (MS)-based analysis of these samples is now available via developed protocols, however, the differences in results with respect to preservation methods needs further investigation. Here we use bladder urothelial carcinoma tissue of two different tumor stages (Ta/T1-non-muscle invasive bladder cancer (NMIBC), and T2/T3-muscle invasive bladder cancer (MIBC)) which, upon sampling, were divided and preserved by FFPE and OCT. Samples were parallel processed from the two methods and proteins were analyzed with label-free quantitative MS. Over 700 and 1200 proteins were quantified in FFPE and OCT samples, respectively. Multivariate analysis indicates that the preservation method is the main source of variation, but also tumors of different stages could be differentiated. Proteins involved in mitochondrial function were overrepresented in OCT data but missing in the FFPE data, indicating that these proteins are not well preserved by FFPE. Concordant results for proteins such as HMGCS2 (uniquely quantified in Ta/T1 tumors), and LGALS1, ANXA5 and plastin (upregulated in T2/T3 tumors) were observed in both FFPE and OCT data, which supports the use of MS technology for biobank samples and encourages the further evaluation of these proteins as biomarkers.De två första författarna delar förstaförfattarskapet</p

Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule

Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-restrained complexing agent (RESCA) method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the RESCA chelator for direct labeling with [18F]AlF. 18 F]AlF. In vivo positron emission tomography/magnetic resonance imaging scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, 18 F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor b (PDGFRb), b ), with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer's high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value [SUV] 0.43 +/- 0.05), with uptake decreasing during recovery (SUV 0.29 +/- 0.03) (p p &lt; 0.0001). [18F]AlF-RESCA-Z09591 18 F]AlF-RESCA-Z09591 accurately detects PDGFRb, b, offering noninvasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development

Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule

Summary: Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-restrained complexing agent (RESCA) method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the RESCA chelator for direct labeling with [18F]AlF. In vivo positron emission tomography/magnetic resonance imaging scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor β (PDGFRβ), with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer’s high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value [SUV] 0.43 ± 0.05), with uptake decreasing during recovery (SUV 0.29 ± 0.03) (p < 0.0001). [18F]AlF-RESCA-Z09591 accurately detects PDGFRβ, offering non-invasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development