[ENT in zero g: the cosmic challenges of otolaryngology]. / Hals, Nase und Ohren in der Schwerelosigkeit: die kosmischen Herausforderungen der HNO-Heilkunde.

Manned spaceflight places special demands on the human body, including the organs in the ENT region. These organs play a critical role in maintaining the health and safety of astronauts in space. In this paper, we review common ENT problems of spaceflight, including upper airway edema, middle ear and mastoid effusions, hearing loss, and dizziness with nausea. We discuss the underlying mechanisms contributing to these complaints, their clinical manifestations, and potential treatment strategies. In addition, we examine the potential impact of these conditions on astronaut health and mission outcomes. Finally, we emphasize the importance of preventive measures and future research in this area to optimize astronaut health and safety on future missions.

Mesoporous Poly(melamine-co-formaldehyde) Particles for Efficient and Selective Phosphate and Sulfate Removal.

Due to the existence-threatening risk to aquatic life and entire ecosystems, the removal of oxyanions such as sulfate and phosphate from anthropogenic wastewaters, such as municipal effluents and acid mine drainage, is inevitable. Furthermore, phosphorus is an indispensable resource for worldwide plant fertilization, which cannot be replaced by any other substance. This raises phosphate to one of the most important mineral resources worldwide. Thus, efficient recovery of phosphate is essential for ecosystems and the economy. To face the harsh acidic conditions, such as for acid mine drainage, an adsorber material with a high chemical resistivity is beneficial. Poly(melamine-co-formaldehyde) (PMF) sustains these conditions whilst its very high amount of nitrogen functionalities (up to 53.7 wt.%) act as efficient adsorption sides. To increase adsorption capacities, PMF was synthesized in the form of mesoporous particles using a hard-templating approach yielding specific surface areas up to 409 m2/g. Different amounts of silica nanospheres were utilized as template and evaluated for the adsorption of sulfate and phosphate ions. The adsorption isotherms were validated by the Langmuir model. Due to their properties, the PMF particles possessed outperforming maximum adsorption capacities of 341 and 251 mg/g for phosphate and sulfate, respectively. Furthermore, selective adsorption of sulfate from mixed solutions of phosphate and sulfate was found for silica/PMF hybrid particles.

Selective Transformation of Nickel-Bound Formate to CO or C-C Coupling Products Triggered by Deprotonation and Steered by Alkali-Metal Ions.

The complexes [LtBu Ni(OCO-κ2 O,C)]M3 [N(SiMe3 )2 ]2 (M=Li, Na, K), synthesized by deprotonation of a nickel formate complex [LtBu NiOOCH] with the corresponding amides M[N(SiMe3 )2 ], feature a NiII -CO2 2- core surrounded by Lewis-acidic cations (M+ ) and the influence of the latter on the behavior and reactivity was studied. The results point to a decrease of CO2 activation within the series Li, Na, and K, which is also reflected in the reactivity with Me3 SiOTf leading to the liberation of CO and formation of a Ni-OSiMe3 complex. Furthermore, in case of K+ , the {[K3 [N(SiMe3 )2 ]2 }+ shell around the Ni-CO2 2- entity was shown to have a large impact on its stabilization and behavior. If the number of K[N(SiMe3 )2 ] equivalents used in the reaction with [LtBu NiOOCH] is decreased from 3 to 0.5, the deprotonated part of the precursor enters a complex reaction sequence with formation of [LtBu NiI (µ-OOCH)NiI LtBu ]K and [LtBu Ni(C2 O4 )NiLtBu ]. The same reaction at higher concentrations additionally led to the formation of a unique hexanuclear NiII complex containing both oxalate and mesoxalate ([O2 C-CO2 -CO2 ]4- ) ligands.

Toward Plasmonic Tunnel Gaps for Nanoscale Photoemission Currents by On-Chip Laser Ablation.

We demonstrate that prestructured metal nanogaps can be shaped on-chip to below 10 nm by femtosecond laser ablation. We explore the plasmonic properties and the nonlinear photocurrent characteristics of the formed tunnel junctions. The photocurrent can be tuned from multiphoton absorption toward the laser-induced strong-field tunneling regime in the nanogaps. We demonstrate that a unipolar ballistic electron current is achieved by designing the plasmonic junctions to be asymmetric, which allows ultrafast electronics on the nanometer scale.

A Biomimetic Nickel Complex with a Reduced CO2 Ligand Generated by Formate Deprotonation and Its Behaviour towards CO2.

Reduced CO2 species are key intermediates in a variety of natural and synthetic processes. In the majority of systems, however, they elude isolation or characterisation owing to high reactivity or limited accessibility (heterogeneous systems), and their formulations thus often remain uncertain or are based on calculations only. We herein report on a Ni-CO22- complex that is unique in many ways. While its structural and electronic features help understand the CO2 -bound state in Ni,Fe carbon monoxide dehydrogenases, its reactivity sheds light on how CO2 can be converted into CO/CO32- by nickel complexes. In addition, the complex was generated by a rare example of formate ß-deprotonation, a mechanistic step relevant to the nickel-catalysed conversion of Hx COyz- at electrodes and formate oxidation in formate dehydrogenases.

Significance of Individual Residues at the Regulatory Site of Yeast Pyruvate Decarboxylase for Allosteric Substrate Activation.

The catalytic activity of the allosteric enzyme pyruvate decarboxylase from yeast is strictly controlled by its own substrate pyruvate via covalent binding at a separate regulatory site. Kinetic studies, chemical modifications, cross-linking, small-angle X-ray scattering, and crystal structure analyses have led to a detailed understanding of the substrate activation mechanism at an atomic level with C221 as the core moiety of the regulatory site. To characterize the individual role of the residues adjacent to C221, we generated variants H92F, H225F, H310F, A287G, S311A, and C221A/C222A. The integrity of the protein structure of the variants was established by small-angle X-ray scattering measurements. The analyses of both steady state and transient kinetic data allowed the identification of the individual roles of the exchanged side chains during allosteric enzyme activation. In each case, the kinetic pattern of activation was modulated but not completely abolished. Despite the crucial role of C221, the covalent binding of pyruvate is not obligate for enzyme activation but is a requirement for a kinetically efficient transition from the inactive to the active state. Moreover, only one of the three histidines guiding the activator molecule to the binding pocket, H310, specifically interacts with C221. H310 stabilizes the thiolate form of C221, ensuring a rapid nucleophilic attack of the thiolate sulfur on C2 of the regulatory pyruvate, thus forming a regulatory dyad. The influence of the other two histidines is less pronounced. Substrate activation is slightly weakened for A287G and significantly retarded for S311A.

Activation of Small Molecules at Nickel(I) Moieties.

The activation and selective transformation of virtually inexhaustible or easy-to-generate chemicals like N2, O2, CO2, CO, H2, or methane gas to value-added products is a lively area of current research, because of its economic relevance as well as its huge ecological impact. Biologists and chemists have put forth a lot of effort toward understanding and modeling the mechanisms of biological small-molecule activation, and in several catalytic cycles proposed for nickel-containing enzymes, nickel(I) plays a key role. In recent years also in synthetic chemistry the huge potential of complex nickel(I) units for the activation and transformation of small molecules has been discovered and exploited. This Perspective highlights some representative examples of nickel(I)-based small-molecule activation, intending to establish awareness of the competencies and scope of nickel(I) compounds.

Efficient Approach for Direct Robust Surface Grafting of Polyethyleneimine onto a Polyester Surface during Moulding.

This paper uses a very effective way for surface modification of thermoplastic polymers during moulding. It is based on a grafting reaction between a thin layer of a functional polymer, deposited on a substrate in advance, and a polymer melt. In this paper, a glycol-modified polyethylene terephthalate (PETG) that was brought in contact with a polyethyleneimine layer during fused filament fabrication is investigated. The focus of this paper is the investigation of the reaction product. Grafting was realised by the formation of stable amide bonds by amidation of ester groups in the main chain of a PETG. XPS investigations revealed that the conversion of amino groups was very high, the distribution was even, and the quantity of amino groups per polyester surface area was still very high. The surface properties of the produced polyester part were mainly characterised by polyethyleneimine. The grafting was able to resist several cycles of extraction in alkaline solutions. The stability was only limited by saponification of the polyester. The degree of surface modification was dependent on the molar mass of polyethyleneimine. This could be rationalised, because grafting only occurred with the one polyethyleneimine molecule that is in close vicinity to the polyester surface when both components come in contact. Fused deposition modelling was chosen as the model process with control over each processing step. However, any other moulding process may be applied, particularly injection moulding for mass production.

Molding Process Retaining Gold Nanoparticle Assembly Structures during Transfer to a Polycarbonate Surface.

The immobilization of gold nanoparticle (AuNP) linear surface assemblies on polycarbonate (PC) melt surface via molding is investigated. The order of the particle assemblies is preserved during the molding process. The assemblies on PC exhibit plasmonic coupling features and dichroic properties. The structure of the assemblies is quantified based on Scanning Electron Microscopy (SEM) and image analysis data using an orientational order parameter. The transfer process from mold to melt shows high structural fidelity. The order parameter of around 0.98 reflects the orientation of the lines and remains unaffected, independent of the injection direction of the melt relative to the particle lines. This is discussed in the frame of fountain flow during injection molding. The particles were permanently fixed and withstood the injection molding process, detachment of the substrate, and extraction in boiling ethanol. The plasmonic particles coupled strongly within the dense nanoparticle lines to produce anisotropic optical properties, as quantified by dichroic ratios of 0.28 and 0.52 using ultraviolet-visible-near-infrared (UV-Vis-NIR) spectroscopy. AuNP line assemblies on a polymer surface may be a basis for plasmonic devices like surface-enhanced Raman scattering (SERS) sensors or a precursor for nanowires. Their embedding via injection molding constitutes an important link between particle-self-assembly approaches for optically functional surfaces and polymer processing techniques.

Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma.

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration. Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed. Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006). Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

Laser-Assisted Direct Grafting of Poly(ethyleneimine) on Poly(methyl methacrylate).

Demand for direct chemical modification of functional material on a surface is increasing in various fields. A new approach for a functionalized surface is investigated by applying a conventional laser in order to generate chemical activation by photothermal energy. Poly(ethyleneimine) (PEI), with a high density of amino groups, is chemically grafted on poly(methyl methacrylate) (PMMA) by irradiation of a CO2 laser (10.6 µm). Laser parameters such as power, scan rate, and focal length are observed to play an important role in order to introduce effective photothermal energy for the chemical reaction between PEI and PMMA. By optimization of laser parameters, the amide compound is produced as a result of the reaction of amine from PEI and the ester of PMMA successfully. The PMMA surface modified with PEI is analyzed by XPS and TOF-SIMS to identify the functional groups. Furthermore, the surface is characterized in terms of wettability, adhesion force, and surface charge for various applications. Finally, reaction with dye and metal on the amine-terminated PMMA shows promising results in supplying a selective and reliable functional substrate.

Patients with COVID-19-associated olfactory impairment also show impaired trigeminal function.

OBJECTIVE: Next to olfactory function, the nose can also perceive chemestetic sensations mediated by the trigeminal nerve. While olfactory dysfunction as a symptom of COVID-19 is well described, there has been little research on the limitation of other nasal sensory inputs due to SARS-CoV-2 infection. The aim of this study was to determine possible limitations of nasal chemesthesis after COVID-19 infection by a psychophysiological diagnostic tool. METHODS: In 65 patients with a PCR-confirmed, former COVID-19 disease, olfaction was tested by means of a sniffin' sticks test, tasting by taste sprays and chemesthesis with a menthol dilution series. The subjective self-assessment of the patients was recorded via a questionnaire. RESULTS: We found a restriction of nasal chemesthesis and the extent correlated with the loss of smell, as well as with the values of the taste score, but not with subjective self-assessment. CONCLUSION: Not only the ability to smell and taste, but also nasal chemesthesis is affected by COVID-19.

Elastomeric microwell-based triboelectric nanogenerators by in situ simultaneous transfer-printing.

Self-powered tactile module-based electronic skins incorporating triboelectric nanogenerator (TENG) appears to be a worthwhile alternative for smart monitoring devices in terms of sustainable energy harvesting. On top of it, ultra-stretchability and detection sensitivity are imperative to mimic human skin. We report, for the first time, a metal-free single electrode TENG-based self-powered tactile module comprising of microwells (diameters 2 µm and 200 nm, respectively) on fluoroelastomer (FKM) and laser induced graphene (LIG) electrodes by in situ simultaneous transfer printing method. Direct imprinting of both the active surface and LIG electrode on a tribonegative FKM has not been attempted before. The resulting triboelectric module exhibits impressive maximum power density of 715 mW m-2, open circuit voltage and maximum output current of 148 V and 9.6 µA respectively for a matching load of 10 MΩ. Moreover, the TENG unit is very robust and sustained high electrical output even at 200% elongation. A dielectric-to-dielectric TENG-based tactile sensor is also constructed using FKM (negative tribolayer) and TiO2 deposited micropatterned PDMS. Resulting tribo-sensor demonstrates remarkable motion and force sensitivity. It can also distinguish subtle human contact force that can simulate skin with high sensitivity and therefore, can be utilized for potential e-skin/bionic skin applications in health and human-machine interfaces.

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies.

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Negative myoclonus as the leading symptom in acute cefepime neurotoxicity.

An 86-year-old woman was diagnosed with hospital-acquired pneumonia with Pseudomonas aeruginosa and treated with cefepime adjusted to her renal clearance. After 4 days, she developed acute-onset negative myoclonus without signs of altered mental status. After ruling out an acute intracranial haemorrhagic or ischaemic stroke as well as other metabolic and endocrine causes of negative myoclonus, the antibiotic was switched to piperacillin/tazobactam due to a suspicion of cefepime neurotoxicity. The patient improved within 24 hours and her symptoms fully resolved within 4 days. These observations suggest a link of the negative myoclonus to acute cefepime neurotoxicity, which may occur without or with minimal alteration of mental status, thus extending its spectrum of clinical presentation.

Persisting olfactory dysfunction improves in patients 6 months after COVID-19 disease.

BACKGROUND: Smell disorders persist in about half of the patients with other symptoms of COVID-19 disease, but the exact duration of the symptoms is yet unknown. Especially, only a few studies used validated olfactory tests for this. AIMS/OBJECTIVES: The aim of this study was to investigate how many patients with olfactory function impairment, which was detected in a validated olfactory test 3 months after COVID-19 disease, showed improvement in olfactory function after 6 months. METHODS: About 26 patients with a PCR-confirmed, former COVID-19 disease, with an impaired olfactory function after three months, were included in the study. The olfactory function was evaluated with the sniffing sticks test, the taste function with taste sprays. RESULTS: Smelling function improved in all but one patient (96%). All measured subitems, i.e. olfactory threshold, identification and discrimination of odours significantly improved. In the whole mouth taste test all patients showed normal taste function. CONCLUSIONS AND SIGNIFICANCE: 6 months after COVID-19 disease, olfactory function improves in just about all patients. Long-term measurements must investigate whether complete regeneration of the olfactory function will occur in all patients.

Electron transfer within ß-diketiminato nickel bromide and cobaltocene redox couples activating CO2.

Reduction of ß-diketiminato nickel(ii) complexes (LtBuNiII) to the corresponding nickel(i) compounds does not require alkali metal compounds but can also be performed with the milder cobaltocenes. LtBuNiBr and Cp2Co have rather similar redox potentials, so that the equilibrium with the corresponding electron transfer compound [LtBuNiIBr][Cp2CoIII] (ETC) clearly lies on the side of the starting materials. Still, the ETC portion can be used to activate CO2 yielding a mononuclear nickel(ii) carbonate complex and ETC can be isolated almost quantitatively from the solutions through crystallisation. The more negative reduction potential of Cp*2Co shifts the equilibrium formed with LtBuNiBr strongly towards the ETC and accordingly the reaction of such solutions with CO2 is much faster.

Upfront Surgery vs. Primary Chemoradiation in an Unselected, Bicentric Patient Cohort with Oropharyngeal Squamous Cell Carcinoma-A Matched-Pair Analysis.

The two pillars of therapy for oropharyngeal squamous cell carcinoma (OPSCC) are upfront surgery and primary chemoradiotherapy. Substantial regional preferences exist with regard to the selection of treatment. Despite new therapeutic approaches, patient survival remains poor, with an approximate overall survival (OS) rate of 50% at five years. This study was conducted to investigate a potential survival benefit depending on the treatment modality in OPSCC patients. We retrospectively collected data of 853 patients with histologically confirmed OPSCC from the Giessen and Maastricht cancer databases. To identify risk factors affecting survival, a Cox-proportional hazard model was applied to 442 patients with complete data sets. Based on this cohort a matched-pair analysis with 158 patients was performed to compare OS rates of patients treated either with upfront surgery or primary chemoradiation. For the collective cohort, patients treated with upfront surgery had significantly improved OS rates compared to patients treated with primary chemoradiation. In the matched-pair analysis adjusted for patients' T-, N- and HPV-status as well as risk profile, we observed that both treatment approaches offered equivalent OS rates. Our study emphasizes that treatment recommendations should be made whenever possible on the basis of side-effect profiles caused by the therapeutic approach used. To draw further conclusions, results of the ongoing "best of" (NCT2984410) study are eagerly awaited, investigating the functional outcome after treatment of OPSCC patients.