Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID-19.

BACKGROUND: The broad-spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis. OBJECTIVES: Isavuconazole plasma concentrations in critically ill ICU patients with or without COVID-19 and invasive fungal infection were determined, and factors for sub-therapeutic drug levels (<1 µg/mL) were evaluated. PATIENTS AND METHODS: Isavuconazole plasma levels were measured as part of therapeutic drug monitoring (TDM) in ICUs of a tertiary hospital. Concentrations determined 20-28 h after previous dosing were defined as trough (Cmin ) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID-19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID-19 status, body mass index (BMI), sepsis-related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement. RESULTS: The mean Cmin of isavuconazole in all patients was 1.64 µg/mL (interquartile range 0.83-2.24 µg/mL, total range 0.24-5.67 µg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 µg/mL. Drug concentrations between patients with or without COVID-19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001). CONCLUSIONS: Isavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.

Risk Stratification of SARS-CoV-2 Breakthrough Infections Based on an Outbreak at a Student Festive Event.

In early 2022, the Coronavirus disease 2019 (COVID-19) remains a global challenge. COVID-19 is caused by an increasing number of variants of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we report an outbreak of SARS-CoV-2 breakthrough infections related to a student festive event with 100 mostly vaccinated guests, which took place in Northern Bavaria, Germany, in October 2021. The data were obtained by retrospective guest interviews. In total, 95 students participated in the study, with 94 being fully vaccinated and 24 reporting infection by the delta variant. Correlation analyses among 15 examined variables revealed that time spent at the event, conversation with the supposed index person, and a homologous viral vector vaccination regime were significant risk factors for infection. Non-significant observations related to higher rates of infection included time since last vaccination, shared use of drinking vessels, and number of individual person-to-person contacts at the event. Our data suggest that a high rate of breakthrough infections with the delta variant occurs if no preventive measures are practiced. To limit infection risk, high-quality testing of participants should be considered a mandatory measure at gatherings, irrespective of the participants' vaccination status.

Regenerative Capacity of the Upside-down Jellyfish Cassiopea xamachana.

This study provides the first observation that umbrellar tissue can lead to the formation of virtually all body structures in jellyfish of the order Rhizostomeae. The regeneration process was observed in two specimens of the upside-down jellyfish Cassiopea xamachana Bigelow, 1892, one housed at the Vienna Zoo, Austria and the other in a laboratory at the University of São Paulo, Brazil. The process was triggered by an injury and ended with the formation of two new sets of body structures. Our observation offers evidence that C. xamachana has a hidden regenerative capacity exceeding that previously recorded.

First description of the life cycle of the jellyfish Rhizostoma luteum (Scyphozoa: Rhizostomeae).

Jellyfish blooms are a significant environmental problem that is increasing and may be influenced by anthropocentric practices such as overfishing, pollution, eutrophication, translocation, climate change, and ocean acidification. Many jellyfish have unknown life cycles leading to these blooms. We describe for the first time, the life cycle of scyphozoan jellyfish Rhizostoma luteum from the planula to the young medusa stages, based on laboratory observations. We also provide a preliminary assessment of temperature related to life stages. Comparisons were made with early life history stages of its sibling species Rhizostoma pulmo and Rhizostoma octopus. The life cycle of R. luteum follows the general pattern of metagenesis of scyphozoans. Scyphistoma culture was maintained in filtered seawater at 17-17.5 °C, salinity 37 and light photoperiod (12:12 h light:dark). Scyphistomae were exposed to an experimental temperature descent for two days to test their survival capacity under severe winter conditions. Only one asexual reproduction mode was observed, which is employed for propagation, consisting of podocyst formation with excystment, subsequent development of scyphistoma, strobilation and liberation of viable ephyra. The development of the ephyra to metaephyra was photodocumented, reaching the metaephyra stage in approximately 21-25 days. Young medusae grow rapidly and maturity was reached after a 3-month post-liberation period with a mean bell diameter of 13.27 ± 2.26 cm and wet weight of 181.53 ± 53 g. The life cycle of R. luteum resembles that of its congeners, with the distinction that it has the unique features of being a brooding species (internal fertilisation with subsequent release of planulae) and under the conditions tested, the predominantly strobilation type observed was monodisc, and not polydisc as with the other two species in the genus Rhizostoma. As R. luteum shows sufficient requisite to form blooms if environmental circumstances change, it is important to understand its life cycle.

The impact of aggressive priming, rumination, and frustration on prison sentencing.

We tested the hypothesis that ruminating about a previous aggressive prime interacts with a subsequent minor frustration to augment aggression. Sixty participants watched a video showing a murder during a bank robbery (the aggressive prime). Those in the rumination condition were asked to write about the video for 20 min. In the no rumination condition, participants were given 20 min to complete an irrelevant task. Participants were then either frustrated or not frustrated. Our results supported the main hypothesis. Relative to the control condition, neither rumination nor frustration alone impacted aggression. Rumination, in combination with a minor frustration, however, increased the recommended prison sentence towards the targets. We discuss the implications of our findings.