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Purpose. This study investigated an inhalation solution containing ectoine, a bacterial-derived extremolyte, for the treatment of acute bronchitis and acute respiratory infections in comparison with saline inhalation solution. Methods. This prospective, controlled, observational study comprised an inclusion visit (day 1), a final visit (day 7), and a follow-up questionnaire (day 17). The treatment itself was administered from day 1 to day 7. The Bronchitis Severity Score, patients’ general health, general effectiveness of the treatment, tolerability, and adverse events were compared between two groups. Results. In total, 135 patients were recruited; 79 patients received ectoine inhalation solution and 56 saline inhalation solution. After treatment, symptom scores decreased significantly in both groups (P < 0.05); the reduction in symptom scores was slightly greater in the ectoine group than in the saline group. The first significant reduction in symptom scores (P < 0.05) occurred earlier in the ectoine group than in the saline group. The differences in the area under the curve for the symptoms of dyspnea and auscultation findings were significant in favor of ectoine (P < 0.05). After treatment, more patients and physicians in the ectoine group assessed their or their patients’ condition as “completely recovered” or “greatly improved” than those in the saline group. Almost all patients and physicians assessed the tolerability of both treatments as “good” or “very good”. Conclusions. Ectoine inhalation solution seems to be slightly more effective than saline inhalation solution for the treatment of acute bronchitis and acute respiratory infections.

Background and Objectives Remimazolam is a new ultra-short-acting benzodiazepine currently being developed for intravenous use in procedural sedation, general anaesthesia, and intensive care unit sedation. Benzodiazepines represent a drug class associated with drug-facilitated sexual assaults, especially in combination with alcohol. Two clinical trials were designed to evaluate the oral bioavailability and pharmacokinetics/pharmacodynamics of remimazolam and to assess the potential for remimazolam misuse in drug-facilitated sexual assaults via oral ingestion. Methods Trial 1 was conducted in 14 healthy volunteers to evaluate the oral bioavailability of remimazolam. Part 1 of trial 2 was conducted in 21 healthy female volunteers to find the minimal biologically active dose of oral remimazolam. Part 2 of trial 2 was conducted in 11 healthy female volunteers to evaluate the pharmacokinetics/pharmacodynamics of oral remimazolam in combination with alcohol. Results Remimazolam undergoes rapid and extensive first-pass metabolism upon oral administration. The oral bioavailability of remimazolam was negligible (2.2% based on total systemic exposure and 1.2% based on maximum plasma concentration). Plasma clearance of both remimazolam and its metabolite was fast (elimination half-life 20‒40 min and 1.75‒2 h, respectively). Alcohol did not appear to inhibit the rapid first-pass metabolism of remimazolam. No clear sedative effects were observed for remimazolam without alcohol. Significant sedation was observed in one of ten subjects after remimazolam 360 mg (18 drug product vials) + 40% v/v alcohol. Conclusion The oral bioavailability of remimazolam is negligible, which—together with its distinct bitter taste—suggests no meaningful potential for misuse in drug-facilitated sexual assaults via oral ingestion, with or without alcohol. Clinical Trial Registration Numbers Trial 1 (NCT04113564) and trial 2 (NCT04113343) both retrospectively registered on 2 October 2019.

The distinction of anterior versus posterior is a crucial first step in animal embryogenesis. In the fly Drosophila, this axis is established by morphogenetic gradients contributed by the mother that regulate zygotic target genes. This principle has been considered to hold true for insects in general but is fundamentally different from vertebrates, where zygotic genes and Wnt signaling are required. We investigated symmetry breaking in the beetle Tribolium castaneum, which among insects represents the more ancestral short-germ embryogenesis. We found that maternal Tc-germ cell-less is required for anterior localization of maternal Tc-axin, which represses Wnt signaling and promotes expression of anterior zygotic genes. Both RNAi targeting Tc-germ cell-less or double RNAi knocking down the zygotic genes Tc-homeobrain and Tc-zen1 led to the formation of a second growth zone at the anterior, which resulted in double-abdomen phenotypes. Conversely, interfering with two posterior factors, Tc-caudal and Wnt, caused double-anterior phenotypes. These findings reveal that maternal and zygotic mechanisms, including Wnt signaling, are required for establishing embryo polarity and induce the segmentation clock in a short-germ insect.

Genetic screens are powerful tools to identify the genes required for a given biological process. However, for technical reasons, comprehensive screens have been restricted to very few model organisms. Therefore, although deep sequencing is revealing the genes of ever more insect species, the functional studies predominantly focus on candidate genes previously identified in Drosophila , which is biasing research towards conserved gene functions. RNAi screens in other organisms promise to reduce this bias. Here we present the results of the iBeetle screen, a large-scale, unbiased RNAi screen in the red flour beetle, Tribolium castaneum , which identifies gene functions in embryonic and postembryonic development, physiology and cell biology. The utility of Tribolium as a screening platform is demonstrated by the identification of genes involved in insect epithelial adhesion. This work transcends the restrictions of the candidate gene approach and opens fields of research not accessible in Drosophila . Unbiased screening for insect gene function has been largely restricted to Drosophila . Here, Schmitt-Engel et al. perform an unbiased large-scale RNAi screen in the red flour beetle Tribolium castaneum to identify putative gene functions.

Although muscle development has been widely studied in Drosophila melanogaster there are still many gaps in our knowledge, and it is not known to which extent this knowledge can be transferred to other insects. To help in closing these gaps we participated in a large-scale RNAi screen that used the red flour beetle, Tribolium castaneum, as a screening platform. The effects of systemic RNAi were screened upon double-stranded RNA injections into appropriate muscle-EGFP tester strains. Injections into pupae were followed by the analysis of the late embryonic/early larval muscle patterns, and injections into larvae by the analysis of the adult thoracic muscle patterns. Herein we describe the results of the first-pass screens with pupal and larval injections, which covered ∼8,500 and ∼5,000 genes, respectively, of a total of ∼16,500 genes of the Tribolium genome. Apart from many genes known from Drosophila as regulators of muscle development, a collection of genes previously unconnected to muscle development yielded phenotypes in larval body wall and leg muscles as well as in indirect flight muscles. We then present the main candidates from the pupal injection screen that remained after being processed through a series of verification and selection steps. Further, we discuss why distinct though overlapping sets of genes are revealed by the Drosophila and Tribolium screening approaches.

IntroductionOral mucositis is a frequent complication of cancer chemotherapy and radiotherapy. Ectoine is a natural extremolyte that can stabilize biological membranes and counteract inflammatory reactions. This study investigated ectoine-containing mouthwash for the prophylaxis and the treatment of oral mucositis. Its effectiveness, tolerability, and safety were compared to those of the local standard-of-care calcium phosphate mouthwash.MethodsThis prospective, active-controlled, observational study was conducted in two study centers in Hungary from January 2016 to October 2017. Sixty patients undergoing chemotherapy were to be recruited and allocated to one of three treatment arms: prophylactic treatment with ectoine (20 patients), active treatment with ectoine (20 patients), or calcium phosphate (20 patients). The study lasted 21 days, comprising four visits on day 0, day 7, day 14, and day 21.ResultsIn all, 45 patients were included in the study (prophylactic ectoine, 10 patients; active ectoine, 20 patients; calcium phosphate, 15 patients). In the prophylactic ectoine group, few mucositis symptoms of mild or moderate severity occurred throughout the study. In the active ectoine and the calcium phosphate groups, symptoms of mild and moderate severity at inclusion were reduced significantly after 14 days of treatment and were mostly resolved at the end of the study. The difference between the active ectoine and the calcium phosphate groups was not significant. According to patients’ assessments, ectoine mouthwash was more effective and tolerable than calcium phosphate mouthwash.ConclusionsEctoine mouthwash is safe, well tolerated, and effective for the active treatment of oral mucositis following chemotherapy. Its effectiveness is comparable to that of calcium phosphate. Patients prefer ectoine mouthwash to calcium phosphate mouthwash.Trial Registration NumberNCT02816515.FundingBitop AG (Dortmund, Germany).Plain Language SummaryPlain language summary available for this article.

Monitoring physical exercises is vital for health promotion, with automated systems becoming standard in personal health surveillance. However, sensor placement variability and unconstrained movements limit their effectiveness. This study proposes the team \"3KA\"'s one-sensor workout activity recognition method using feature extraction and data augmentation in 2ndWEAR Dataset Challenge. From raw acceleration, angle and signal magnitude vector features were derived, followed by extraction of statistical, fractal/spectral, and higher-order differential features. A fused dataset combining left/right limb data was created, and augmented via sensor rotation and axis inversion. We utilized a soft voting model combining Hist Gradient Boosting with balanced weights and Extreme Gradient Boosting without. Under group 5-fold evaluation, the model achieved 58.83\\% macro F1 overall (61.72% arm, 55.95% leg). ANOVA F-score showed fractal/spectral features were most important for arm-based recognition but least for leg-based. The code to reproduce the experiments is publicly available via: https://github.com/Khanghcmut/WEAR\\_3K

This paper introduces a non-invasive, pose-based pipeline for classifying normal (eating snacks, sitting quietly, walking, using phone) and unusual (head banging, throwing things, attacking, biting) behaviors using 2D skeleton data from five subjects. Seventeen keypoints are first normalized by centering on the hip midpoint and scaling by the average shoulder-to-shoulder and hip-to-hip distances to ensure consistent scale and orientation across subjects. Time-series features are then extracted with TSFEL and customized features, after which a preliminary Categorical Boosting (CatBoost) model ranks feature importances, and the top 500 features are retained. A CatBoostClassifier trained under Leave-One-Subject-Out cross-validation achieves an average accuracy of 76.29% with a per-class Macro F1 score of 75.06%. Main contributions include an end-to-end framework for detecting both normal and unusual behaviors from 2D skeleton sequences, a comprehensive analysis of discriminative time-series features that drive classification performance, and empirical evidence demonstrating strong cross-subject generalization under Leave-One-Subject-Out evaluation.

Background Insect pest control is challenged by insecticide resistance and negative impact on ecology and health. One promising pest specific alternative is the generation of transgenic plants, which express double stranded RNAs targeting essential genes of a pest species. Upon feeding, the dsRNA induces gene silencing in the pest resulting in its death. However, the identification of efficient RNAi target genes remains a major challenge as genomic tools and breeding capacity is limited in most pest insects impeding whole-animal-high-throughput-screening. Results We use the red flour beetle Tribolium castaneum as a screening platform in order to identify the most efficient RNAi target genes. From about 5,000 randomly screened genes of the iBeetle RNAi screen we identify 11 novel and highly efficient RNAi targets. Our data allowed us to determine GO term combinations that are predictive for efficient RNAi target genes with proteasomal genes being most predictive. Finally, we show that RNAi target genes do not appear to act synergistically and that protein sequence conservation does not correlate with the number of potential off target sites. Conclusions Our results will aid the identification of RNAi target genes in many pest species by providing a manageable number of excellent candidate genes to be tested and the proteasome as prime target. Further, the identified GO term combinations will help to identify efficient target genes from organ specific transcriptomes. Our off target analysis is relevant for the sequence selection used in transgenic plants.

Although muscle development has been widely studied in Drosophila melanogaster there are still many gaps in our knowledge, and it is not known to which extent this knowledge can be transferred to other insects. To help in closing these gaps we participated in a large-scale RNAi screen that used the red flour beetle, Tribolium castaneum, as a screening platform. The effects of systemic RNAi were screened upon double-stranded RNA injections into appropriate muscle-EGFP tester strains. Injections into pupae were followed by the analysis of the late embryonic/early larval muscle patterns, and injections into larvae by the analysis of the adult thoracic muscle patterns. Herein we describe the results of the first-pass screens with pupal and larval injections, which covered ~8,500 and ~5,000 genes, respectively, of a total of ~16,500 genes of the Tribolium genome. Apart from many genes known from Drosophila as regulators of muscle development, a collection of genes previously unconnected to muscle development yielded phenotypes in larval body wall and leg muscles as well as in indirect flight muscles. We then present the main candidates from the pupal injection screen that remained after being processed through a series of verification and selection steps. Further, we discuss why distinct though overlapping sets of genes are revealed by the Drosophila and Tribolium screening approaches.