Cytology-based Cancer Surgery of the Head and Neck (CyCaS-HN): a prospective, randomized, controlled clinical trial

Purpose Liquid-based cytology (LBC) is routinely used in gynecology but is rarely applied in head and neck oncology though many suspicious lesions are easily accessible. While several studies have evaluated the potential use of LBC for early detection and molecular characterization of head and neck squamous cell carcinomas (HNSCCs), no study investigated its potential role in surgical management and therapy planning so far. Methods Twenty-fve patients with cT1-2 squamous cell carcinomas of the oral cavity and oropharynx were prospectively enrolled in this study and were randomized to two treatment arms: in the control arm, a diagnostic panendoscopy with incisional biopsy was followed by a second operation with transoral tumor resection±neck dissection and tracheostomy. In the intervention arm, patients underwent LBC diagnostics and in case of a positive result received one single operation with panendoscopy and incisional biopsy for confrmation of LBC result by rapid section histology followed by transoral tumor resection±neck dissection and tracheostomy in the same session. Results Time between clinical diagnosis and defnitive surgical treatment was signifcantly shorter in the intervention group compared with the control group (p<0.0001). Additionally, time of hospitalization (p<0.0001) and cumulative operation time (p=0.062) were shorter in the intervention group. No signifcant diferences in overall, progression-free, and diseasespecifc survival were observed. Conclusion Cytology-based cancer surgery is a promising therapeutic strategy that can potentially be considered for a well-defned group of early-stage HNSCC patients and help to avoid repetitive general anesthesia, shorten the diagnosis-totreatment interval and spare operation as well as hospitalization time

Assessing the Use of Telepresence-Guided Video-Based Head and Neck Ultrasound Training: A Step towards Minimizing Dependence on Human Resources?

The acquisition of ultrasound skills is an essential part of any medical student’s education. University access restrictions in the context of the COVID-19 pandemic have highlighted the need for digitization in teaching. However, teaching manual skills in online courses has proven to be challenging, not least in terms of human resources. Therefore, the aim of this study was to set up a hybrid head and neck ultrasound course consisting of a preface of video-based self-study followed by supportive instruction by a tutor in telepresence and to evaluate the quality, effectiveness, and feasibility of this teaching method. Thirty-five students were shown video tutorials on systematic ultrasound of the neck course. Learning outcomes were analyzed using self-assessment questionnaires and external assessment by an experienced ultrasonographer. All participants demonstrated statistically significant learning improvement (p < 0.001) when comparing self-assessment scores before and after training. The mean self-assessment scores increased from 13.8 to 26.6 for the telepresence-guided group, from 16.6 to 27.3 for the web-based group, and from 14.0 to 26.2 for the in-person group. The external observer assessment also showed improvement, with mean scores of 46.7, 48.1, and 46.5, respectively. Overall results did not significantly differ when comparing different instruction modalities. A telepresence-guided video-based ultrasound course is well suited to teaching ultrasound skills similar to in-person courses and allows a more resource-efficient targeting of student needs

Time and space-resolved quantification of plasma membrane sialylation for measurements of cell function and neurotoxicity

While there are many methods to quantify the synthesis, localization, and pool sizes of proteins and DNA during physiological responses and toxicological stress, only few approaches allow following the fate of carbohydrates. One of them is metabolic glycoengineering (MGE), which makes use of chemically modified sugars (CMS) that enter the cellular biosynthesis pathways leading to glycoproteins and glycolipids. The CMS can subsequently be coupled (via bio-orthogonal chemical reactions) to tags that are quantifiable by microscopic imaging. We asked here, whether MGE can be used in a quantitative and time-resolved way to study neuronal glycoprotein synthesis and its impairment. We focused on the detection of sialic acid (Sia), by feeding human neurons the biosynthetic precursor N-acetyl-mannosamine, modified by an azide tag. Using this system, we identified non-toxic conditions that allowed live cell labeling with high spatial and temporal resolution, as well as the quantification of cell surface Sia. Using combinations of immunostaining, chromatography, and western blotting, we quantified the percentage of cellular label incorporation and effects on glycoproteins such as polysialylated neural cell adhesion molecule. A specific imaging algorithm was used to quantify Sia incorporation into neuronal projections, as potential measure of complex cell function in toxicological studies. When various toxicants were studied, we identified a subgroup (mitochondrial respiration inhibitors) that affected neurite glycan levels several hours before any other viability parameter was affected. The MGE-based neurotoxicity assay, thus allowed the identification of subtle impairments of neurochemical function with very high sensitivity.publishe

Binding site feature description of 2-substituted benzothiazoles as potential AcrAB-TolC efflux pump inhibitors in E. coli

The resistance-nodulation-division (RND) family efflux pumps are important in the antibiotic resistance of Gram-negative bacteria. However, although a number of bacterial RND efflux pump inhibitors have been developed, there has been no clinically available RND efflux pump inhibitor to date. A set of BSN-coded 2-substituted benzothiazoles were tested alone and in combinations with ciprofloxacin (CIP) against the AcrAB-TolC overexpressor Escherichia coli AG102 clinical strain. The results indicated that the BSN compounds did not show intrinsic antimicrobial activity when tested alone. However, when used in combinations with CIP, a reversal in the antibacterial activity of CIP with up to 10-fold better MIC values was observed. In order to describe the binding site features of these BSN compounds with AcrB, docking studies were performed using the CDocker method. The performed docking poses and the calculated binding energy scores revealed that the tested compounds BSN-006, BSN-023, and BSN-004 showed significant binding interactions with the phenylalanine-rich region in the distal binding site of the AcrB binding monomer. Moreover, the tested compounds BSN-006 and BSN-023 possessed stronger binding energies than CIP, verifying that BSN compounds are acting as the putative substrates of AcrB. © 2015, Taylor & Francis

Reasons to be cheerful? Reflections on GPs' responses to depression

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes