Objective. After laryngectomy, the breathing resistance of heat and moisture exchangers may limit exercise capacity. Breathing gas analysis during cardiopulmonary exercise testing is not possible using regular masks. This study tested the feasibility of cardiopulmonary exercise testing with a heat and moisture exchanger in situ, using an in-house designed connector. Additionally, we explored the effect of different heat and moisture exchanger resistances on exercise capacity in this group. Methods. Ten participants underwent two cardiopulmonary exercise tests using their daily life heat and moisture exchanger (0.3 hPa or 0.6 hPa) and one specifically developed for activity (0.15 hPa). Heat and moisture exchanger order was randomised and blinded.Results. All participants completed both tests. No (serious) adverse events occurred. Only four subjects reached a respiratory exchange ratio of more than 1.1 in at least one test. Maximum exercise levels using heat and moisture exchangers with different resistances did not differ. Conclusion. Cardiopulmonary exercise testing in laryngectomees with a heat and moisture exchanger is feasible; however, the protocol does not seem appropriate to reach this group's maximal exercise capacity. Lowering heat and moisture exchanger resistance does not increase exercise capacity in this sample.
Echinoderm mass mortality events shape marine ecosystems by altering the dynamics among major benthic groups. The sea urchin Diadema antillarum, virtually extirpated in the Caribbean in the early 1980s by an unknown cause, recently experienced another mass mortality beginning in January 2022. We investigated the cause of this mass mortality event through combined molecular biological and veterinary pathologic approaches comparing grossly normal and abnormal animals collected from 23 sites, representing locations that were either affected or unaffected at the time of sampling. Here, we report that a scuticociliate most similar to Philaster apodigitiformis was consistently associated with abnormal urchins at affected sites but was absent from unaffected sites. Experimentally challenging naïve urchins with a Philaster culture isolated from an abnormal, field-collected specimen resulted in gross signs consistent with those of the mortality event. The same ciliate was recovered from treated specimens postmortem, thus fulfilling Koch’s postulates for this microorganism. We term this condition D. antillarum scuticociliatosis.
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Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
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