Corrigendum to “Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics” [Biomaterials 192 (2019) 551–559]

Entwicklung eines ICF-basierten Leitfadens für die Beurteilung funktioneller Aspekte bei Kopf-Hals-Tumoren

Funktionelle Beeintrachtigungen bei Kopf-Hals-Tumoren werden bisher im klinischen Alltag selten standardisiert erhoben. Klinische Studien mit der Zielgrose Funktionserhalt bei KHT verwenden viele verschiedene Instrumente. Die Ergebnisse sind deshalb oft schlecht vergleichbar und lassen zu wenig klinische Schlussfolgerungen zu. Es war daher notwendig und Ziel dieser Studie, die nach bisheriger Evidenz und interdisziplinarem Expertenkonsens am besten geeigneten Instrumente zur Beurteilung von Funktionsfahigkeit bei KHT zu identifizieren und Empfehlungen fur deren Verwendung in einem Leitfaden zusammenzustellen. In Vorstudien wurde unter Verwendung festgelegter Kriterien eine Vorauswahl an Ins…

Die Rolle von Thrombospondin-1 bei Biomaterialintegration von Implantaten aus porösem Polyethylen in vivo

Randomized controlled single‐blinded clinical trial of functional voice outcome after vascular targeting KTP laser microsurgery of early laryngeal cancer

Abstract Background Local control rate (LCR) of early glottic cancer is high after radiation therapy or transoral laser microsurgery (TLM). The aim of this study was to investigate functional voice outcome after TLM using a microvessel‐ablative potassium‐titanyl‐phosphate (KTP) laser in comparison with a gold standard cutting CO2 laser. Methods The primary end point of this prospective, randomized, single‐blinded, clinical phase II study with control group was voice outcome during a follow‐up of 6 months assayed by Voice Handicap Index (VHI‐30)‐questionnaires in patients with unilateral high‐grade dysplasia, carcinoma in situ or early glottic cancer undergoing TLM‐KTP (n = 8) or TLM‐CO2 (n …

Time‐dependent induction of vascular oxidative stress, inflammation, endothelial dysfunction and high blood pressure by aircraft noise exposure in mice

The role of structured surgical planning in the learning process of functional endoscopic sinus surgery

Gentamicin alters Akt-expression and its activation in the guinea pig cochlea

Gentamicin treatment induces hair cell death or survival in the inner ear. Besides the well-known toxic effects, the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway was found to be involved in cell protection. After gentamicin application, the spatiotemporal expression patterns of Akt and its activated form (p-Akt) were determined in male guinea pigs. A single dose of 0.1 mL gentamicin (4 mg/ear/animal) was intratympanically injected. The auditory brainstem responses (ABRs) were recorded prior to application and 1, 2 and 7 days afterward. At these three time points the cochleae (n=10 in each case) were removed, transferred to fixative and embedded in paraffin. Seven ears were used as u…

Surface Modification of Porous Polyethylene Implants with an Albumin-Based Nanocarrier-Release System

Background: Porous polyethylene (PPE) implants are used for the reconstruction of tissue defects but have a risk of rejection in case of insufficient ingrowth into the host tissue. Various growth factors can promote implant ingrowth, yet a long-term gradient is a prerequisite for the mediation of these effects. As modification of the implant surface with nanocarriers may facilitate a long-term gradient by sustained factor release, implants modified with crosslinked albumin nanocarriers were evaluated in vivo. Methods: Nanocarriers from murine serum albumin (MSA) were prepared by an inverse miniemulsion technique encapsulating either a low- or high-molar mass fluorescent cargo. PPE implants …

Modulation of Exposure to Static Magnetic Field Affects Targeted Therapy of Solid Tumors In Vivo

Background Static magnetic fields (SMF) exhibit antitumoral activity and enhance the efficacy of chemotherapy by opening the tumor-blood barrier. This study aimed to analyze different SMF-exposure protocols on epidermal growth factor receptor (EGFR)-overexpressing tumors, as well as their combination with cetuximab. Materials and methods Experiments were performed in skinfold chamber preparations of C57Bl/6-and CD-1nu/nu mice bearing LLC-1 tumors. Animals were exposed to 587 mT magnetic field following different exposure protocols. A subgroup received additional cetuximab injections. Using in vivo-fluorescence microscopy and planimetry, tumor angiogenesis, growth and microcirculation were r…

Dexamethasone prevents hearing loss by restoring glucocorticoid receptor expression in the guinea pig cochlea

Objectives/Hypothesis Dexamethasone is widely used in the treatment of various inner ear diseases. However, knowledge about its direct impact on glucocorticoid receptor (GR) expression is still limited. Study Design Prospective animal study in male guinea pigs. Methods A therapeutic concentration of dexamethasone (8mg/mL) or a physiological concentration of NaCl (0.9% solution) were intratympanically injected into the ears of guinea pigs (n = 10 in each case) 14 hours prior to 90 dB noise exposure (1 hour). Eighteen ears were exposed to noise only. Seven untreated ears were used as controls. Auditory brainstem responses were recorded prior to noise exposure or treatment and 2 hours thereaft…

Die Rolle der strukturierten Operationsplanung im Lernprozess der funktionell endoskopischen Nasennebenhöhlenchirurgie

Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice

Epidemiological studies showed that traffic noise has a dose-dependent association with increased cardiovascular morbidity and mortality. Whether microvascular dysfunction contributes significantly to the cardiovascular health effects by noise exposure remains to be established. The connection of inflammation and immune cell interaction with microvascular damage and functional impairment is also not well characterized. Male C57BL/6J mice or gp91phox−/y mice with genetic deletion of the phagocytic NADPH oxidase catalytic subunit (gp91phox or NOX-2) were used at the age of 8 weeks, randomly instrumented with dorsal skinfold chambers and exposed or not exposed to aircraft noise for 4 days. Pro…

SARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 da…

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma

Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood. Broad variations of chemo and radiation resistance mechanisms are known to date. This study describes the development of a standardized, high-throughput in vitro assay to a…

In vivo analysis of noise dependent activation of white blood cells and microvascular dysfunction in mice

This article contains supporting information on data collection for the research article entitled “Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice” by Eckrich et al. We found that noise-induced stress triggered microvascular dysfunction via involvement of innate immune-derived reactive oxygen species. In this article, we present the instrumentation of mice with dorsal skinfold chambers for in vivo microscopic imaging of blood flow, interaction of leukocytes with the vascular wall (also by fluorescent labelling of blood cells) and vessel diameter. In addition, we explain the preparation of cerebral arterioles for measurement of…

A method for determining precise electrical hearing thresholds in cochlear implant users

A psychoacoustic procedure designed for the precise assessment of perceptional threshold (T-level) in cochlear implant (CI) users is presented. The impact of this procedure on speech perception was investigated.Individual T-level measurements were obtained with the proposed procedure and three different speech processor fitting conditions were applied: (1) fitting familiar to the subject, T-levels unchanged, (2) T-level set to thresholds determined with the new procedure, (3) T-level set to thresholds determined with the new procedure, but T-level is decreased by 10 clinical units (CU). The impact of the different fitting conditions was measured by means of categorical loudness scaling (CLS…

Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics

Abstract Multidrug-resistant bacterial infections are a global health threat. Nanoparticles are thus investigated as novel antibacterial agents for clinical practice, including wound dressings and implants. We report that nanoparticles' bactericidal activity strongly depends on their physical binding to pathogens, including multidrug-resistant primary clinical isolates, such as Staphylococcus aureus , Klebsiella pneumoniae or Enterococcus faecalis . Using controllable nanoparticle models, we found that nanoparticle-pathogen complex formation was enhanced by small nanoparticle size rather than material or charge, and was prevented by 'stealth' modifications. Nanoparticles seem to preferentia…

Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea.

Intratympanic gentamicin therapy has become a popular treatment modality for Meniere's disease (MD) through controlled elimination of vertigo spells caused by the balance organ. However, the known ototoxic properties of aminoglycosides lead to cochlear damage. In order to gain more information about cellular preferences for aminoglycoside accumulation within the cochlea, gentamicin was immuno histochemically localized by light microscopy in male guinea pigs 1 and 7 days after intratympanic application (n = 8 ears/incubation time). Differences in the gentamicin-specific cellular storage capacities were quantified by determination of the local immuno staining intensities. Gentamicin was detec…

Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(II) complexes

Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridi…

The German hearing in noise test

The aims of this study were to develop a German Hearing In Noise Test (HINT) using the same methodology as with previous HINT tests; to develop sentence lists for measuring speech reception thresholds (SRTs); and to determine test-retest reliability and norms for measures obtained under headphones.The following steps were followed: develop and record sentences, synthesise masking noise, determine the performance-intensity (PI) function, equalise sentence difficulty in the masking noise. Form sentence lists of equal difficulty. Measure SRTs for normal hearing individuals to determine practice/learning effects, test-retest reliability, and norms.Three groups of adults (median age = 25 years) …

Early Alterations of Endothelial Nitric Oxide Synthase Expression Patterns in the Guinea Pig Cochlea After Noise Exposure.

Constitutively expressed endothelial nitric oxide synthase (eNOS) is supposed to play a role in noise-induced nitric oxide (NO)-production. It is commonly known that intense noise exposure results in inducible NOS (iNOS) expression and increased NO-production, but knowledge about a contribution of the eNOS isoform is still lacking. Effects of noise exposure on eNOS immunolabeling were determined in male guinea pigs ( n=24). For light microscopic analysis, 11 animals were exposed to 90 dB for 1 hr and 6 animals were used as controls. After exposure, eNOS immunostaining was performed on paraffin sections, and the staining intensities were quantified for 4 cochlear regions. For electron micro…

The role of thrombospondin-1 in biomaterial integration of porous polyethylene implants in vivo

Targeting Cancer Chemotherapy Resistance by Precision Medicine-Driven Nanoparticle-Formulated Cisplatin.

Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline fromiin silico/ito analytical andiin vitro/ito overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion cha…