TY - JOUR A1 - Moratin, Helena A1 - Ickrath, Pascal A1 - Scherzad, Agmal A1 - Meyer, Till Jasper A1 - Naczenski, Sebastian A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes JF - Nanomaterials N2 - Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed. KW - zinc oxide nanoparticles KW - immunomodulation KW - T cell subpopulations Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234016 SN - 2079-4991 VL - 11 IS - 3 ER - TY - JOUR A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Deep neck infections with and without mediastinal involvement: treatment and outcome in 218 patients JF - European Archives of Oto-Rhino-Laryngology N2 - Purpose Infections of the deep neck, although becoming scarcer due to the widespread use of antibiotics, still represent a dangerous and possibly deadly disease, especially when descending into the mediastinum. Due to the different specialities involved in the treatment and the heterogenous presentation of the disease, therapeutic standard is still controversial. This study analyzes treatment and outcome in these patients based on a large retrospective review and proposes a therapeutic algorithm. Methods The cases of 218 adult patients treated with deep neck abscesses over a 10-year period at a tertiary university hospital were analyzed retrospectively. Clinical, radiological, microbiological and laboratory findings were compared between patients with and without mediastinal involvement. Results Forty-five patients (20.64%) presented with abscess formation descending into the mediastinum. Those patients had significantly (all items p < 0.0001) higher rates of surgical interventions (4.27 vs. 1.11) and tracheotomies (82% vs. 3.4%), higher markers of inflammation (CRP 26.09 vs. 10.41 mg/dl), required more CT-scans (3.58 vs. 0.85), longer hospitalization (39.78 vs 9.79 days) and more frequently needed a change in antibiotic therapy (44.44% vs. 6.40%). Multi-resistant pathogens were found in 6.67% vs. 1.16%. Overall mortality rate was low with 1.83%. Conclusion Despite of the high percentage of mediastinal involvement in the present patient collective, the proposed therapeutic algorithm resulted in a low mortality rate. Frequent CT-scans, regular planned surgical revisions with local drainage and lavage, as well as an early tracheotomy seem to be most beneficial regarding the outcome. KW - tracheotomy KW - deep neck infection KW - mediastinitis KW - surgical drainage KW - microbiology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266814 SN - 1434-4726 VL - 279 IS - 3 ER - TY - JOUR A1 - Kraus, Fabian A1 - Hackenberg, Stephan A1 - Shehata-Dieler, Wafaa A1 - Hagen, Rudolf T1 - High-sensitivity FEES\(^{®}\) with the professional image enhancement technology "PIET" JF - European Archives of Oto-Rhino-Laryngology N2 - Purpose Flexible endoscopic evaluation of swallowing (FEES\(^{®}\)) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the "professional image enhancement technique" (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES\(^{®}\) procedure. Methods Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES\(^{®}\) was performed and recorded with the two systems during daily routine. Results Performing an image enhancement during FEES\(^{®}\) is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected. Conclusion PIET proved to be non-inferior to NBI during image enhancement FEES\(^{®}\). So far, image enhancement FEES\(^{®}\) was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications. KW - aspiration KW - high-sensitivity FEES KW - narrow band imaging (NBI) KW - professional image enhancement technique (PIET) KW - dysphagia Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266822 SN - 1434-4726 VL - 279 IS - 1 ER - TY - JOUR A1 - Gehrke, Thomas A1 - Hackenberg, Stephan A1 - Tecle, Nyat A1 - Hagen, Rudolf A1 - Scherzad, Agmal T1 - Tuberculosis in the Head and Neck: Changing Trends and Age-Related Patterns JF - The Laryngoscope N2 - Objective To evaluate changing trends in patient collectives, age-related patterns of manifestation, and diagnostic pathways of patients with extrapulmonary head and neck tuberculosis (TB), and to provide strategies to fasten diagnosis in these patients. Study design Case control study. Methods A 10-year retrospective analysis of 35 patients diagnosed with extrapulmonary TB in the head and neck at a tertiary university institution from 2009 to 2019, with special focus on the influence of the patient's age on consideration of TB and clinical patterns. Results The vast majority of patients younger than 40 years had their origin in countries with high TB burden (P = .0003), and TB was considered very early as a differential diagnosis (P = .0068), while most patients older than 40 years were domestic citizens initially suspected for a malignancy, who more often had an underlying immunosuppressive condition (0.0472). Most frequent manifestations in both groups were the lymph nodes, larynx, and oropharynx. Surprisingly, no differences in the rates of open TB or history of TB infection in the family anamnesis were found. Conclusion The two groups of patients found most often are younger patients migrating from regions with high TB burden and elderly domestic patients suffering from immunosuppressive conditions, with the latter often being misdiagnosed as malignancies. TB remains an important but difficult differential diagnosis, due to the initially unspecific symptoms and the great variety in the presentation of manifestations in the head and neck. KW - lymph node tuberculosis KW - Tuberculosis KW - head and neck KW - extrapulmonary tuberculosis KW - laryngeal tuberculosis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257524 VL - 131 IS - 12 ER - TY - JOUR A1 - Meyer, Till Jasper A1 - Scherzad, Agmal A1 - Moratin, Helena A1 - Gehrke, Thomas Eckert A1 - Killisperger, Julian A1 - Hagen, Rudolf A1 - Wohlleben, Gisela A1 - Polat, Bülent A1 - Dembski, Sofia A1 - Kleinsasser, Norbert A1 - Hackenberg, Stephan T1 - The radiosensitizing effect of zinc oxide nanoparticles in sub-cytotoxic dosing is associated with oxidative stress in vitro JF - Materials N2 - Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP\(_{20 nm}\) and ZnO-NP\(_{100 nm}\) was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP\(_{20 nm}\) or 20 µg/mL of ZnO-NP\(_{100 nm}\) in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP\(_{100 nm}\) increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP\(_{20 nm}\). ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP\(_{100 nm}\), an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect. KW - zinc oxide nanoparticles KW - irradiation KW - oxidative DNA damage KW - head and neck squamous cell carcinoma Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193897 SN - 1996-1944 VL - 12 IS - 24 ER - TY - JOUR A1 - Fischer, Jonas A1 - Dirks, Johannes A1 - Klaussner, Julia A1 - Haase, Gabriele A1 - Holl-Wieden, Annette A1 - Hofmann, Christine A1 - Hackenberg, Stephan A1 - Girschick, Hermann A1 - Morbach, Henner T1 - Effect of clonally expanded PD-1\(^h\)\(^i\)\(^g\)\(^h\) CXCR5-CD4+ peripheral T Helper cells on B cell differentiation in the joints of patients with antinuclear antibody-positive juvenile idiopathic arthritis JF - Arthritis & Rheumatology N2 - Objective Antinuclear antibody (ANA)–positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the precise role of CD4+ T cells in promoting local B cell activation is unknown. This study was undertaken to determine the phenotype and function of synovial CD4+ T cells that promote aberrant B cell activation in JIA. Methods Flow cytometry was performed to compare the phenotype and cytokine patterns of PD-1\(^h\)\(^i\)\(^g\)\(^h\)CD4+ T cells in the synovial fluid (SF) of patients with JIA and T follicular helper cells in the tonsils of control individuals. TCRVB next-generation sequencing was used to analyze T cell subsets for signs of clonal expansion. The functional impact of these T cell subsets on B cells was examined in cocultures in vitro. Results Multidimensional flow cytometry revealed the expansion of interleukin-21 (IL-21) and interferon-γ (IFNγ)–coexpressing PD-1\(^h\)\(^i\)\(^g\)\(^h\)CXCR5–HLA–DR+CD4+ T cells that accumulate in the joints of ANA-positive JIA patients. These T cells exhibited signs of clonal expansion with restricted T cell receptor clonotypes. The phenotype resembled peripheral T helper (Tph) cells with an extrafollicular chemokine receptor pattern and high T-bet and B lymphocyte–induced maturation protein 1 expression, but low B cell lymphoma 6 expression. SF Tph cells, by provision of IL-21 and IFNy, skewed B cell differentiation toward a CD21\(^l\)\(^o\)\(^w\)\(^/\)\(^-\)CD11c+ phenotype in vitro. Additionally, SF Tph cell frequencies correlated with the appearance of SF CD21\(^l\)\(^o\)\(^w\)\(^/\)\(^-\)CD11c+CD27–IgM– double-negative (DN) B cells in situ. KW - medicine Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256607 VL - 74 IS - 1 ER - TY - JOUR A1 - Sivarajan, Rinu A1 - Kessie, David Komla A1 - Oberwinkler, Heike A1 - Pallmann, Niklas A1 - Walles, Thorsten A1 - Scherzad, Agmal A1 - Hackenberg, Stephan A1 - Steinke, Maria T1 - Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin JF - Frontiers in Cellular and Infection Microbiology N2 - To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC\(^-\). Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens. KW - human nasal epithelial cells KW - human tracheo-bronchial epithelial cells KW - human airway mucosa tissue models KW - adenylate cyclase toxin KW - Bordetella pertussis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-253302 SN - 2235-2988 VL - 11 ER - TY - JOUR A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Risk factors for children requiring adenotonsillectomy and their impact on postoperative complications: a retrospective analysis of 2000 patients JF - Anaesthesia N2 - Adenotonsillectomies are commonly performed procedures and sleep‐disordered breathing is becoming increasingly important as an indication for surgery. Because of the higher risks in patients with obstructive sleep apnoea, the required level of postoperative care for these patients is currently under discussion, and better identification of patients at risk may reduce unnecessary postoperative monitoring. To evaluate the influence of obstructive sleep apnoea, and other risk factors, on peri‐operative complications in children requiring adenotonsillectomy, we performed a retrospective case‐control study that included 1995 patients treated between January 2009 and June 2017. In our analysis, young age (OR 3.8, 95%CI 2.1–7.1), low body weight (OR 2.6, 95%CI 1.5–4.4), obstructive sleep apnoea (OR 2.4, 95%CI 1.5–3.8), pre‐existing craniofacial or syndromal disorders (OR 2.3, 95%CI 1.4–3.8) and adenotonsillectomy, compared with adenoidectomy alone, (OR 7.9, 95%CI 4.7–13.1) were identified as risk factors for complications during or after surgery, p < 0.001. All 13 patients suffering from complications more than 3 h postoperatively had obstructive sleep apnoea plus at least one more of these risk factors. Patients at risk of postoperative complications can therefore be identified by several criteria pre‐operatively, and should be monitored postoperatively using pulse oximetry overnight. For all other patients, postoperative observation on a surgical ward without extra monitoring is sufficient. Admission to paediatric intensive care should be reserved for patients suffering serious intra‐operative complications. KW - adenotonsillectromy KW - monotoring KW - obstructive sleep apnoea KW - paediatrics KW - retrospective KW - risk factors Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204787 VL - 74 IS - 12 ER - TY - JOUR A1 - Scherzad, Agmal A1 - Meyer, Till A1 - Kleinsasser, Norbert A1 - Hackenberg, Stephan T1 - Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity Short Running Title: Genotoxicity of ZnO NPs JF - Materials N2 - Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival. KW - zinc oxide nanoparticles KW - genotoxicity KW - DNA damage KW - ROS KW - autophagy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169948 VL - 10 IS - 12 ER - TY - JOUR A1 - Bianchi, Maria A1 - Sivarajan, Rinu A1 - Walles, Thorsten A1 - Hackenberg, Stephan A1 - Steinke, Maria T1 - Susceptibility of primary human airway epithelial cells to Bordetella pertussis adenylate cyclase toxin in two- and three-dimensional culture conditions JF - Innate Immunity N2 - The human pathogen Bordetella pertussis targets the respiratory epithelium and causes whooping cough. Its virulence factor adenylate cyclase toxin (CyaA) plays an important role in the course of infection. Previous studies on the impact of CyaA on human epithelial cells have been carried out using cell lines derived from the airways or the intestinal tract. Here, we investigated the interaction of CyaA and its enzymatically inactive but fully pore-forming toxoid CyaA-AC– with primary human airway epithelial cells (hAEC) derived from different anatomical sites (nose and tracheo-bronchial region) in two-dimensional culture conditions. To assess possible differences between the response of primary hAEC and respiratory cell lines directly, we included HBEC3-KT in our studies. In comparative analyses, we studied the impact of both the toxin and the toxoid on cell viability, intracellular cAMP concentration and IL-6 secretion. We found that the selected hAEC, which lack CD11b, were differentially susceptible to both CyaA and CyaA-AC–. HBEC3-KT appeared not to be suitable for subsequent analyses. Since the nasal epithelium first gets in contact with airborne pathogens, we further studied the effect of CyaA and its toxoid on the innate immunity of three-dimensional tissue models of the human nasal mucosa. The present study reveals first insights in toxin–cell interaction using primary hAEC. KW - Adenylate cyclase toxin KW - cyclic adenosine monophosphate KW - human respiratory epithelial cells KW - IL-6 KW - Bordetella pertussis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219849 SN - 1753-4259 SN - 1753-4267 VL - 27 IS - 1 SP - 89-98 ER - TY - JOUR A1 - Tecle, Nyat-Eyob A1 - Hackenberg, Stephan A1 - Scheich, Matthias A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Gehrke, Thomas T1 - Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases JF - European Journal of Pediatrics N2 - Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1–18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved. Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient’s outcome. What is Known: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery. What is New: • The focus identification has no impact on patient’s outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved. KW - lateral neck abscesses KW - children KW - focus of infection KW - surgery Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324179 VL - 182 IS - 1 ER - TY - JOUR A1 - Hackenberg, Stephan A1 - Meyer, Till Jasper A1 - Häfner, Johannes A1 - Scheich, Matthias A1 - Stöth, Manuel A1 - Al-Tinawi, Fadi A1 - Neun, Tilmann A1 - Mlynski, Robert A1 - Hagen, Rudolf A1 - Scherzad, Agmal T1 - Surgical management of tympanojugular paragangliomas using the flexible CO\(_2\) laser JF - European Archives of Oto-Rhino-Laryngology N2 - Purpose Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser. Methods Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. Results The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. Conclusion The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view. KW - tympanojugular paraganglioma KW - tympanic paraganglioma KW - jugular paraganglioma KW - surgical management of paraganglioma KW - laser surgery KW - flexible CO2 laser Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324164 VL - 279 IS - 12 ER - TY - JOUR A1 - Stefanakis, Mona A1 - Bassler, Miriam C. A1 - Walczuch, Tobias R. A1 - Gerhard-Hartmann, Elena A1 - Youssef, Almoatazbellah A1 - Scherzad, Agmal A1 - Stöth, Manuel Bernd A1 - Ostertag, Edwin A1 - Hagen, Rudolf A1 - Steinke, Maria R. A1 - Hackenberg, Stephan A1 - Brecht, Marc A1 - Meyer, Till Jasper T1 - The impact of tissue preparation on salivary gland tumors investigated by Fourier-transform infrared microspectroscopy JF - Journal of Clinical Medicine N2 - Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows. KW - formalin KW - fixation KW - tissue preparation KW - salivary gland neoplasia KW - FTIR spectroscopy KW - principal component analysis KW - discriminant analysis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304887 SN - 2077-0383 VL - 12 IS - 2 ER - TY - JOUR A1 - Bassler, Miriam C. A1 - Knoblich, Mona A1 - Gerhard-Hartmann, Elena A1 - Mukherjee, Ashutosh A1 - Youssef, Almoatazbellah A1 - Hagen, Rudolf A1 - Haug, Lukas A1 - Goncalves, Miguel A1 - Scherzad, Agmal A1 - Stöth, Manuel A1 - Ostertag, Edwin A1 - Steinke, Maria A1 - Brecht, Marc A1 - Hackenberg, Stephan A1 - Meyer, Till Jasper T1 - Differentiation of salivary gland and salivary gland tumor tissue via Raman imaging combined with multivariate data analysis JF - Diagnostics N2 - Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary. KW - salivary gland tumor KW - confocal Raman imaging KW - principal component analysis KW - discriminant analysis KW - multivariate data analysis KW - molecular diagnostics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355558 SN - 2075-4418 VL - 14 IS - 1 ER - TY - JOUR A1 - Moratin, Helena A1 - Thöle, Anna A1 - Lang, Josephine A1 - Ehret Kasemo, Totta A1 - Stöth, Manuel A1 - Hagen, Rudolf A1 - Scherzad, Agmal A1 - Hackenberg, Stephan T1 - Ag- but not ZnO-nanoparticles disturb the airway epithelial barrier at subtoxic concentrations JF - Pharmaceutics N2 - Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air–liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs. KW - epithelial barrier KW - nanoparticles KW - tight junctions KW - zinc oxide KW - silver Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357403 SN - 1999-4923 VL - 15 IS - 10 ER -