Robustness of the honeybee neuro-muscular octopaminergic system in the face of cold stress.

In recent decades, our planet has undergone dramatic environmental changes resulting in the loss of numerous species. This contrasts with species that can adapt quickly to rapidly changing ambient conditions, which require physiological plasticity and must occur rapidly. The Western honeybee (Apis mellifera) apparently meets this challenge with remarkable success, as this species is adapted to numerous climates, resulting in an almost worldwide distribution. Here, coordinated individual thermoregulatory activities ensure survival at the colony level and thus the transmission of genetic material. Recently, we showed that shivering thermogenesis, which is critical for honeybee thermoregulation, depends on octopamine signaling. In this study, we tested the hypothesis that the thoracic neuro-muscular octopaminergic system strives for a steady-state equilibrium under cold stress to maintain endogenous thermogenesis. We can show that this applies for both, octopamine provision by flight muscle innervating neurons and octopamine receptor expression in the flight muscles. Additionally, we discovered alternative splicing for AmOARß2. At least the expression of one isoform is needed to survive cold stress conditions. We assume that the thoracic neuro-muscular octopaminergic system is finely tuned in order to contribute decisively to survival in a changing environment.

Efficacy and tolerability of regorafenib in pretreated patients with progressive CNS grade 3 or 4 gliomas.

BACKGROUND: The phase 2 REGOMA trial suggested an encouraging overall survival benefit in glioblastoma patients at first relapse treated with the multikinase inhibitor regorafenib. Here, we evaluated the efficacy and side effects of regorafenib in a real-life setting. METHODS: From 2018 to 2021, 30 patients with progressive WHO CNS grade 3 or 4 gliomas treated with regorafenib (160 mg/day; first 3 weeks of each 4-week cycle) with individual dose adjustment depending on toxicity were retrospectively identified. Side effects were evaluated according to the Common Terminology Criteria for Adverse Events (version 5.0). MRI was obtained at baseline and after every second cycle. Tumor progression was assessed according to RANO criteria. After regorafenib initiation, the median PFS and OS were calculated. RESULTS: The median number of treatment lines before regorafenib was 2 (range 1-4). Most patients (73%) had two or more pretreatment lines. At first relapse, 27% of patients received regorafenib. A total of 94 regorafenib cycles were administered (median 2 cycles; range 1-9 cycles). Grade 3 and 4 side effects were observed in 47% and 7% of patients, respectively, and were not significantly increased in patients with two or more pretreatments (P > 0.05). The most frequent grade 3 or 4 side effects were laboratory abnormalities (62%). PFS was 2.6 months (range 0.8-8.2 months), and the OS was 6.2 months (range 0.9-24 months). CONCLUSIONS: In patients with progressive WHO grade 3 or 4 gliomas, predominantly with two pretreatment lines or more, regorafenib seems to be effective despite considerable grade 3 or 4 side effects.

Antimicrobial Susceptibility Profile of Rare Anaerobic Bacteria.

Anaerobes play an important role in clinically relevant infections and resistance is increasing worldwide. We tested 120 rare anaerobic isolates belonging to 16 genera for antimicrobial resistance using the agar dilution method and compared those results to the time-saving E-test method. The susceptibility data for 12 antimicrobial substances (benzylpenicillin, ampicillin/sulbactam, piperacillin/tazobactam, imipenem, meropenem, cefoxitin, metronidazole, moxifloxacin, clindamycin, doxycycline, tigecycline, eravacycline) were collected. Susceptibility testing showed low resistance to ß-lactam/ß-lactamase inhibitor combinations and no resistance to carbapenems and tigecycline. We observed moderate to high rates of resistance to moxifloxacin and clindamycin which differed depending on the methodology used. The essential and categorical agreement was over 90% for ampicillin/sulbactam, meropenem, moxifloxacin, and tigecycline. For metronidazole and clindamycin, the essential agreement was below 90% but the categorical agreement was near or above 90%. Penicillin presented with the lowest categorical agreement of 86.7% and a very high very major error rate of 13.3%. The resistance rates reported in this study are concerning and show the importance of routine susceptibility testing. Further investigations are necessary to determine the reason for high error rates and how to improve susceptibility testing of fastidious anaerobes.

Trait Self-Control Outperforms Trait Fatigue in Predicting MS Patients' Cortical and Perceptual Responses to an Exhaustive Task.

Patients with multiple sclerosis (PwMS) frequently suffer from fatigue, but this debilitating symptom is not yet fully understood. We propose that self-control can be conceptually and mechanistically linked to the fatigue concept and might help explain some of the diversity on how PwMS who suffer from fatigue deal with this symptom. To test this claim, we first assessed how cortical oxygenation and measures of motor and cognitive state fatigue change during a strenuous physical task, and then we tested the predictive validity of trait fatigue and trait self-control in explaining the observed changes. A sample of N = 51 PwMS first completed a test battery to collect trait measures of fatigue and self-control. PwMS then performed an isometric hand contraction task at 10% of their maximum voluntary contraction until exhaustion while we repeatedly assessed ratings of perceived cognitive and motor exertion. In addition, we continuously measured oxygenation of the prefrontal cortex (PFC) using functional near-infrared spectroscopy. Linear mixed-effect models revealed significant increases in perceived motor and cognitive exertion, as well as increases in PFC oxygenation. Hierarchical stepwise regression analyses showed that higher trait self-control predicted a less steep increase in PFC oxygenation and perceived cognitive exertion, while trait fatigue did not predict change in any dependent variable. These results provide preliminary evidence for the suggested link between self-control and fatigue. As self-control can be enhanced with training, this finding possibly has important implications for devising nonpharmacological interventions to help patients deal with symptoms of fatigue.