Biology subjects

Rentsch, K.

Publications and source records attributed to Rentsch, K..

4 recordsLinked to original sources

bioRxiv2026

Persistent Staphylococcus aureus in human musculoskeletal tissues despite targeted antibiotic therapy

Staphylococcus aureus is a leading cause of musculoskeletal infection with frequent recurrence despite surgery and antibiotic therapy. Its persistence in human tissues under antibiotic pressure remains unclear. We performed longitudinal in situ analyses of matched tissue samples before and during therapy from patients undergoing repeated surgery using advanced imaging and tissue-based metagenomics. S. aureus remained detectable in all samples--including culture-negative specimens--and whole-genome sequencing confirmed persistence of the infecting strain. Antibiotic initiation reduced bacterial burden by 1.0Slog10 bacteria/mm3 but residual loads stabilized thereafter. Quantitative imaging identified a culture detection threshold ([~]103bacteria/mm3), indicating that culture negativity reflects diagnostic sensitivity limits rather than true bacterial clearance. Persistence under antibiotic therapy was associated with high baseline burden and intracellular sequestration, whereas long-term persistence was characterized by predominantly extracellular bacteria capable of driving relapse. These findings reveal sustained tissue persistence despite apparent microbiological clearance and guide precision strategies to target resilient bacterial reservoirs.

microbiology↗

bioRxiv2021

Time to recover from daily caffeine intake.

Caffeine elicits widespread effects in the central nervous system and is the most frequently consumed psychostimulant worldwide. First evidence indicates that, during daily intake, the elimination of caffeine may slow down and the primary metabolite, paraxanthine, may accumulate. The neural impact of such adaptions is virtually unexplored. In this report, we leveraged the data of a laboratory study with N= 20 participants and three within-subject conditions: caffeine (150 mg caffeine x 3/day x 10 days), placebo (150 mg mannitol x 3/day x 10 days), and withdrawal (caffeine x 9 days, afterwards placebo x 1 day). Using liquid chromatography-mass spectrometry coupled with tandem mass spectrometry, we determined the course of salivary caffeine and paraxanthine, measured regularly at day 10. We assessed grey matter (GM) intensity and cerebral blood flow (CBF) in the withdrawal condition as compared to their changes in caffeine in our previous report. The results indicate high remaining levels of paraxanthine and of caffeine carried overnight during daily intake, and the levels of paraxanthine remained higher than in placebo during withdrawal. After 36 h of withdrawal, the previously reported caffeine-induced GM reduction was partially mitigated, while CBF was elevated compared to placebo. Our findings unveil that conventional daily caffeine intake does not provide sufficient time to clear up psychoactive compounds and restore cerebral responses, even after 36 hours of abstinence. They also suggest investigating consequences of a paraxanthine accumulation during daily caffeine intake.

pharmacology and toxicology↗

bioRxiv2020

Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial

BackgroundAdolescents frequently consume caffeine with unknown consequences on sleep and circadian rhythms. In adults, the evidence indicates that caffeine acutely reduces homeostatic sleep pressure and delays the circadian timing system. ObjectiveHere, we investigated the acute effects of caffeine intake on the developing sleep-wake regulatory system of teenagers. DesignIn a double-blind randomized crossover laboratory study, 18 teenagers (16.1 {+/-} 1 years old, pubertal development scale [PDS]: 2.76 {+/-} 0.35) ingested 80 mg caffeine (vs placebo) four hours prior to bedtime. Until bedtime, participants regularly filled in the Karolinska Sleepiness Scale and gave saliva samples to measure melatonin secretion. During nighttime, we quantified homeostatic sleep need by the electroencephalographically derived amount of slow wave sleep duration (SWS). After sleep, participants rated sleep quality by the Leeds Sleep Evaluation Questionnaire. ResultsWhile participants felt less sleepy after caffeine vs. placebo (P=0.038), their ratings of sleep quality were not strongly affected by the treatment. However, objectively, SWS was on average reduced by [~]20 min after caffeine vs. placebo (P=0.026). This caffeine-induced reduction was more pronounced in those individuals with more SWS under placebo (regression: P=0.042; standardized beta=0.622, P=0.011), even if controlling for habitual caffeine intake or pubertal stage (PDS). In melatonin onsets we observed both delays and advances in response to caffeine. This variance could partly be explained by differences in relative dose (i.e., mg caffeine/kg of bodyweight): the higher the relative dose, the more likely were delays (regression: P=0.01; standardized beta=0.592, P=0.01). ConclusionsIn teenagers, evening caffeine intake of already 80 mg (i.e. [~]8fl oz of common energy drinks) is sufficient to promote alertness at the costs of subsequent sleep. These costs might be more pronounced in adolescents with a higher need for SWS. Moreover, caffeine might disturb the circadian timing system, consequently hampering the balanced interplay of sleep-wake regulatory components. Sources of SupportMarie-Heim-Voegtlin Grant of the Swiss National Science Foundation (SNSF) PMPDP1_171364

neuroscience↗

bioRxiv2019

Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake

To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, it is unknown whether such a regular intake pattern affects timing and quality of wakefulness, as regulated by an interplay of circadian and sleep-homeostatic mechanisms. Thus, we investigated the effects of daily caffeine intake and its withdrawal on circadian rhythms and wake-promotion in 20 male young habitual caffeine consumers. We applied a double-blind, within-subject design with a caffeine (150 mg, 3 x daily), a placebo, and a withdrawal condition each lasting ten days. Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep, as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h under controlled laboratory conditions. Neither the time course of melatonin (i.e., onset, amplitude, or area under the curve) nor the time course of cortisol were significantly affected by caffeine intake or its withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses, as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both, placebo and caffeine conditions. Thus, the typical timing of habitual caffeine intake in humans may not necessarily shift circadian phase nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.

neuroscience↗