Etiology and Differential Diagnoses of Nuchal Tumors: A Study of 61 Cases.

BACKGROUND/AIM: Compared to other cervical localizations, masses of the nuchal region are rare in the clinical practice of otolaryngologists. This study presents the relevant etiologies of nuchal tumors. PATIENTS AND METHODS: This study included 61 cases (5.3%) from 1,150 consecutive cervical biopsies/neck tumor excisions between 2010 and 2022. Lipomatosis or Madelung fat neck diagnoses were excluded. RESULTS: Seventy-seven percent of the biopsies included lymph node tissue. Among the patients, 26 were female and 35 were male. The average diameter of the tumors was 3.5 cm (1.5-9 cm). Of the 33 non-malignant formations (54%, 42.3 years), lymphadenopathy (e.g., toxoplasmosis and tuberculosis) was found in 58% of cases. Lipomas were most common among benign tumors (8 out of 14). Malignant tumors (46%, 63.4 years) included lymphomas (10 cases, 6 recurrences) and metastases (18 cases). The metastases were predominantly squamous cell carcinomas of the pharynx (9 cases, 5 recurrences) and the skin (7 cases, 4 recurrences), as well as two cases of adenocarcinomas from the lung and pancreas. CONCLUSION: Indications of the malignant genesis of a nuchal mass include older patient age and a history of carcinomas in the head and neck region. In carcinomas of the posterior and parietal scalp and neck skin, the nuchal region should be included in the staging and follow-up examinations.

Encapsulation of Pioglitazone into Polymer-Nanoparticles for Potential Treatment of Atherosclerotic Diseases.

Atherosclerosis is one of the most urgent global health subjects, causes millions of deaths worldwide, and is associated with enormous healthcare costs. Macrophages are the root cause for inflammatory onset and progression of the disease but are not addressed by conventional therapy. Therefore, we used pioglitazone, which is a drug initially used for diabetes therapies, but at the same time has great potential regarding the mitigation of inflammation. As yet, this potential of pioglitazone cannot be exploited, as drug concentrations at the target site in vivo are not sufficient. To overcome this shortcoming, we established PEG-PLA/PLGA-based nanoparticles loaded with pioglitazone and tested them in vitro. Encapsulation of the drug was analyzed by HPLC and revealed an outstanding encapsulation efficiency of 59% into the nanoparticles, which were 85 nm in size and had a PDI of 0.17. Further, uptake of our loaded nanoparticles in THP-1 macrophages was comparable to the uptake of unloaded nanoparticles. On the mRNA level, pioglitazone-loaded nanoparticles were superior to the free drug by 32% in increasing the expression of the targeted receptor PPAR-γ. Thereby the inflammatory response in macrophages was ameliorated. In this study, we take the first step toward an anti-inflammatory, causal antiatherosclerotic therapy, using the potential of the already established drug pioglitazone, and enable it to enrich at the target site by using nanoparticles. An additional crucial feature of our nanoparticle platform is the versatile modifiability of ligands and ligand density, to achieve an optimal active targeting effect in the future.

Fast One-Step Fabrication of Highly Regular Microscrolls with Controllable Surface Morphology.

Although rolling origami technology has provided convenient access to three-dimensional (3D) microstructure systems, the high yield and scalable construction of complex rolling structures with well-defined geometry without impeding functionality has remained challenging. The straightforward, one-step fabrication that uses external mechanical stress to scroll micrometer thick, flexible planar films with centimeter lateral dimensions into tubular or spiral geometry within a few seconds is demonstrated. The method allows controlling the scrolls' diameter, number of windings and nanostructured surface morphology, and is applicable to a wide range of functional materials. The obtained 3D structures are highly promising for various applications including sensors, actuators, microrobotics, as well as energy storage and electronic devices.

First mitogenome phylogeny of the sun bear Helarctos malayanus reveals a deep split between Indochinese and Sundaic lineages.

The sun bear Helarctos malayanus is one of the most endangered ursids, and to date classification of sun bear populations has been based almost exclusively on geographic distribution and morphology. The very few molecular studies focussing on this species were limited in geographic scope. Using archival and non-invasively collected sample material, we have added a substantial number of complete or near-complete mitochondrial genome sequences from sun bears of several range countries of the species' distribution. We here report 32 new mitogenome sequences representing sun bears from Cambodia, Thailand, Peninsular Malaysia, Sumatra, and Borneo. Reconstruction of phylogenetic relationships revealed two matrilines that diverged ~295 thousand years ago: one restricted to portions of mainland Indochina (China, Cambodia, Thailand; "Mainland clade"), and one comprising bears from Borneo, Sumatra, Peninsular Malaysia but also Thailand ("Sunda clade"). Generally recent coalescence times in the mitochondrial phylogeny suggest that recent or historical demographic processes have resulted in a loss of mtDNA variation. Additionally, analysis of our data in conjunction with shorter mtDNA sequences revealed that the Bornean sun bear, classified as a distinct subspecies (H. m. euryspilus), does not harbor a distinctive matriline. Further molecular studies of H. malayanus are needed, which should ideally include data from nuclear loci.

Green Synthesis and Antiproliferative Activity of Gold Nanoparticles of a Controlled Size and Shape Obtained Using Shock Wave Extracts from Amphipterygium adstringens.

In this study, green chemistry was used as a tool to obtain gold nanoparticles using Amphipterygium adstringens extracts as a synthesis medium. Green ethanolic and aqueous extracts were obtained using ultrasound and shock wave-assisted extraction. Gold nanoparticles with sizes ranging between 100 and 150 nm were obtained with ultrasound aqueous extract. Interestingly, homogeneous quasi-spherical gold nanoparticles with sizes between 50 and 100 nm were achieved with shock wave aqueous-ethanolic extracts. Furthermore, 10 nm gold nanoparticles were obtained by the traditional methanolic macerate extraction method. The physicochemical characteristics, morphology, size, stability, and Z potential of the nanoparticles were determined using microscopic and spectroscopic techniques. The viability assay in leukemia cells (Jurkat) was performed using two different sets of gold nanoparticles, with final IC50 values of 87 µM and 94.7 µM, reaching a maximum cell viability decrease of 80% The results do not indicate a significant difference between the cytotoxic effects produced by the gold nanoparticles synthesized in this study and vincristine on normal lymphoblasts (CRL-1991).

Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release Applications Via Rapid In Situ Gelation.

Water-free preparation of protein delivery systems has the potential to overcome the limitations of hydrogel depot systems such as off-target reactions, functional group hydrolysis, and limited loading capacity. However, a major roadblock in the development and use of these systems is administration as implantation is often required. In this study, we developed a biodegradable and water-free injectable protein delivery system via inverse electron demand Diels-Alder reaction between norbornene- and tetrazine-functionalized four-armed poly(ethylene glycol) macromonomers. 1:1 mixtures of these precursors gelled rapidly in situ, taking less than 11 s to reach their gelation point. Methyl substitution of tetrazine slowed the gelation time and increased the cross-linking density, whereas oxygen incorporation into norbornene changed the mechanical properties. Introduction of hydrolytically cleavable groups enabled biodegradability. Using phenyl carbamate and phenyl carbonate ester groups, we could tune the stability. Controlled release of the protein surrogate glucose oxidase was achieved over a period of 500 days. The novel preparation method presented here is a promising step toward the development of water-free injectable protein depots for controlled drug delivery.

Metabolic engineering of Aspergillus niger to enhance production of ethanol.

This work describes the genetic transformation of a strain of Aspergillus niger with five different constructs containing 16 different heterologous genes, coding for four oxidoreductases, two cellobiohydrolases, one endoglucanase, one ß-glucosidase, six enzymes involved in xylose metabolism, and two enzymes involved in fermentation. The aim was to try and engineer a consolidated bioprocessing in A. niger. The fungus already contains most of these enzymes and we only enhanced endogenous activities. We recovered nine transformants containing all genes, as indicated by polymerase chain reaction (PCR). To confirm that the products of the genes were functional, we measured the activity of five different enzymes in all the strains, and they all showed enhanced activity over the wild-type (wt) strain. The strains were grown on carboxymethyl cellulose (CMC) and xylan as substrates, and they produced considerably more ethanol than the wt. The levels of ethanol production were comparable to those reported in the literature.

Blue Turns to Gray: Paleogenomic Insights into the Evolutionary History and Extinction of the Blue Antelope (Hippotragus leucophaeus).

The blue antelope (Hippotragus leucophaeus) is the only large African mammal species to have become extinct in historical times, yet no nuclear genomic information is available for this species. A recent study showed that many alleged blue antelope museum specimens are either roan (Hippotragus equinus) or sable (Hippotragus niger) antelopes, further reducing the possibilities for obtaining genomic information for this extinct species. While the blue antelope has a rich fossil record from South Africa, climatic conditions in the region are generally unfavorable to the preservation of ancient DNA. Nevertheless, we recovered two blue antelope draft genomes, one at 3.4× mean coverage from a historical specimen (∼200 years old) and one at 2.1× mean coverage from a fossil specimen dating to 9,800-9,300 cal years BP, making it currently the oldest paleogenome from Africa. Phylogenomic analyses show that blue and sable antelope are sister species, confirming previous mitogenomic results, and demonstrate ancient gene flow from roan into blue antelope. We show that blue antelope genomic diversity was much lower than in roan and sable antelope, indicative of a low population size since at least the early Holocene. This supports observations from the fossil record documenting major decreases in the abundance of blue antelope after the Pleistocene-Holocene transition. Finally, the persistence of this species throughout the Holocene despite low population size suggests that colonial-era human impact was likely the decisive factor in the blue antelope's extinction.

Effect of Shock Waves on the Growth of Aspergillus niger Conidia: Evaluation of Germination and Preliminary Study on Gene Expression.

Shock waves, as used in medicine, can induce cell permeabilization, genetically transforming filamentous fungi; however, little is known on the interaction of shock waves with the cell wall. Because of this, the selection of parameters has been empirical. We studied the influence of shock waves on the germination of Aspergillus niger, to understand their effect on the modulation of four genes related to the growth of conidia. Parameters were varied in the range reported in protocols for genetic transformation. Vials containing conidia in suspension were exposed to either 50, 100 or 200 single-pulse or tandem shock waves, with different peak pressures (approximately 42, 66 and 83 MPa). In the tandem mode, three delays were tested. To equalize the total energy, the number of tandem "events" was halved compared to the number of single-pulse shock waves. Our results demonstrate that shock waves do not generate severe cellular effects on the viability and germination of A. niger conidia. Nevertheless, increase in the aggressiveness of the treatment induced a modification in four tested genes. Scanning electron microscopy revealed significant changes to the cell wall of the conidia. Under optimized conditions, shock waves could be used for several biotechnological applications, surpassing conventional techniques.

Investigation of the Impact of Hydrolytically Cleavable Groups on the Stability of Poly(ethylene glycol) Based Hydrogels Cross-Linked via the Inverse Electron Demand Diels-Alder (iEDDA) Reaction.

Eight-armed poly(ethylene glycol) (PEG) hydrogels cross-linked via inverse electron demand Diels-Alder reaction between norbornene and tetrazine groups are promising materials for long-term protein delivery. While a controlled release over 265 days is achieved for 15% w/v hydrogels in the previous study, the material shows high stability over 500 days despite having cleavable ester linkages between the PEG macromonomers and their functionalities. In this study, the hydrolyzable ester linkers in the PEG-norbornene precursor structure are exchanged to reduce the degradation time. To this end, 3,6-epoxy-1,2,3,6-tetrahydrophthalimide, phenyl carbamate, carbonate ester, and phenyl carbonate ester are introduced as degradable functional groups. Oscillatory shear experiments reveal that they are not affected the in situ gelation. All hydrogel types have gel points of less than 20 s even at a low polymer concentration of 5% w/v. Hydrogels with varying polymer concentrations have similar mesh sizes, all of which fell in the range of 4-12 nm. The inclusion of phenyl carbonate ester accelerates degradation considerably, with complete dissolution of 15% w/v hydrogels after 302 days of incubation in phosphate buffer (pH 7.4). Controlled release of 150 kDa fluorescein isothiocyanate-dextran over a period of at least 150 days is achieved with 15% w/v hydrogels.

Enzyme-triggered antigen release enhances cross-presentation by dendritic cells.

Nanoparticles hold great potential as vaccine carriers due to their highly versatile structure and the possibility to influence intracellular trafficking and antigen presentation by their design. In this study, we developed a nanoparticulate system with a new enzyme-triggered antigen release mechanism. For this novel approach, nanoparticle and model antigen ovalbumin were linked with a substrate of the early endosomal protease cathepsin S. This construct enabled the transfer of antigens delivered to bone marrow-derived dendritic cells from the endo-lysosomal compartments in the cytosol. Consecutively, our particles enhanced cross-presentation on dendritic cells and subsequently promoted a stronger activation of CD8+ T cells. Our findings suggest that enzyme-triggered antigen release allows the endosomal escape of the antigen, leading to increased MHC-I presentation. Since T cell immunity is central for the control of viral infections and cancer, this release mechanism offers a promising approach for the development of both prophylactic and therapeutic vaccines.

[Contemporary use of instruments during clinical examination in German ENT departments and private practices]. / Einsatz von Instrumenten bei der klinischen Untersuchung in deutschen HNO-Abteilungen und Privatpraxen heutzutage.

BACKGROUND: The classical forehead reflector as traditionally used by ear, nose, and throat (ENT) physicians for the ENT examination is now iconic for doctors in general. It is unknown which instruments are currently used in Germany to clinically examine ENT patients. Therefore, this study aims to present results of a survey about commonly used instruments. MATERIALS AND METHODS: An evaluation of 321 questionnaires from ENT doctors working in general and university hospitals (172) and in private practices (149) was performed. RESULTS: The ENT mirror examination is nowadays carried out with a self-illuminating headlamp with battery and/or light guide cable. Approximately 20% of respondents also use a forehead mirror. The microscope is used by 90% of doctors to examine the ears; a rigid endoscope was used in 53.3% to examine the larynx, epipharynx (41.1%), and the nose/sinuses (34.6%). Flexible endoscopes and otoscopes are used only rarely. CONCLUSION: The self-illuminating headlamp, which is more often wireless in eastern Germany, has largely replaced the classical forehead reflector, with which doctors younger than 40 years were no longer trained. At least some organs are also examined very regularly with the microscope or rigid endoscope. The flexible endoscope and otoscope are used much less frequently overall, mainly by younger physicians and ENT doctors working in hospitals. The diagnostic potential of flexible endoscopy may be compromised by the outpatient remuneration structures in Germany.

In Situ Forming iEDDA Hydrogels with Tunable Gelation Time Release High-Molecular Weight Proteins in a Controlled Manner over an Extended Time.

Off-target interactions between reactive hydrogel moieties and drug cargo as well as slow reaction kinetics and the absence of controlled protein release over an extended period of time are major drawbacks of chemically cross-linked hydrogels for biomedical applications. In this study, the inverse electron demand Diels-Alder (iEDDA) reaction between norbornene- and tetrazine-functionalized eight-armed poly(ethylene glycol) (PEG) macromonomers was used to overcome these obstacles. Oscillatory shear experiments revealed that the gel point of a 15% (w/v) eight-armed PEG hydrogel with a molecular weight of 10 kDa was less than 15 s, suggesting the potential for fast in situ gelation. However, the high-speed reaction kinetics result in a risk of premature gel formation that complicates the injection process. Therefore, we investigated the effect of polymer concentration, temperature, and chemical structure on the gelation time. The cross-linking reaction was further characterized regarding bioorthogonality. Only 11% of the model protein lysozyme was found to be PEGylated by the iEDDA reaction, whereas 51% interacted with the classical Diels-Alder reaction. After determination of the mesh size, fluorescein isothiocyanate-dextran was used to examine the release behavior of the hydrogels. When glucose oxidase was embedded into 15% (w/v) hydrogels, a controlled release over more than 250 days was achieved. Overall, the PEG-based hydrogels cross-linked via the fast iEDDA reaction represent a promising material for the long-term administration of biologics.

Tonsillectomy as a Prevention Strategy in the Light of Increasing Incidence of Oropharyngeal Cancer - a Research of Current Literature.

BACKGROUND/AIM: While in many Western countries the number of tonsillectomies decreases significantly, there is an increasing incidence of oropharyngeal carcinomas. For, obviously, removal of the tonsils will reduce individual risk for tonsil cancer, the question of tonsillectomy as a prevention strategy is suggested. This study focused on this question by carrying out a literature research. MATERIALS AND METHODS: A literature research was performed (www.pubmed.gov; Search words: tonsillectomy, oropharyngeal cancer, tonsil cancer, prevention) without applying additional filters. RESULTS: Out of the 16 identified studies, three population-based studies were evaluated. Individual incidence of tonsil cancer is significantly lower after removal of tonsils; however, risk elimination by tonsillectomy has not been proven. One of the studies revealed increasing numbers of base of the tongue cancer after previous tonsillectomy. CONCLUSION: The increase in oropharynx carcinomas can currently be attributed not to the decreasing tonsillectomy rates, but to the increase in HPV infections. A previous tonsillectomy reduces the individual risk of developing tonsil carcer. Tonsillectomy as prevention for oropharyngeal cancer cannot be recommended and may even be a disadvantage concerning base of the tongue cancers.

Single-crystal-to-single-crystal phase transitions of commensurately modulated sodium saccharinate 1.875-hydrate.

This work reports reversible, single-crystal-to-single-crystal phase transitions of commensurately modulated sodium saccharinate 1.875-hydrate [Na(sac)(15/8)H2O]. The phases were studied in the temperature range 298 to 20 K. They exhibit complex disordered states. An unusual reentrant disorder has been discovered upon cooling through a phase transition at 120 K. The disordered region involves three sodium cations, four water molecules and one saccharinate anion. At room temperature, the structure is an eightfold superstructure that can be described by the superspace group C2/c(0σ20)s0 with q = (0, 3/4, 0). It demonstrates maximum disorder with the disordered chemical entities having slightly different but close to 0.50:0.50 disorder component ratios. Upon cooling, the crystal tends to an ordered state, smoothly reaching a unified disorder component ratio of around 0.90:0.10 for each of the entities. Between 130 and 120 K a phase transition occurs involving a sudden increase of the disorder towards the disorder component ratio 0.65:0.35. Meanwhile, the space group and general organization of the structure are retained. Between 60 and 40 K there is another phase transition leading to a twinned triclinic phase. After heating the crystal back to room temperature its structure is the same as before cooling, indicating a complete reversibility of the phase transitions.

[Second opinion process for tonsillectomy and tonsillotomy: analysis of the quantitative and qualitative justifying conditions]. / Zweitmeinungsverfahren für die Tonsillektomie und Tonsillotomie: eine Analyse der rechtfertigenden quantitativen und qualitativen Voraussetzungen.

BACKGROUND: In 2017, the Federal Joint Committee determined tonsillectomy and hysterectomy in non-oncologic diseases as well as tonsillotomy for second opinion procedure. We discuss the suitability of tonsillectomy and tonsillotomy for the second opinion procedure on its quantitative and qualitative characteristics. MATERIALS AND METHODS: Data from the Federal Statistical Office concerning numbers of cases were evaluated. Numbers and regional distribution of ENT-specialists providing second opinion were analyzed by websites of Associations of SHI Physicians. RESULTS: Between 2005 and 2018a significant decrease in tonsillectomy cases from 119 808 to 42 548 is observable that is by far not compensated by increasing tonsillotomy numbers from 4659 (2007) to 18 369. At the same time, surgical procedure rates at regional levels remain volatile. 218 ENT-specialists in 142 towns provide second opinion. On basic of case numbers in 2018a relationship of 1(ENT-specialist): 280 (tonsillectomy/tonsillotomy patients) results (range from 1:90 to 1:800). CONCLUSIONS: On the background of decreasing surgical rates tonsil surgery does not comply with the requirements of second opinion procedure. Reachability of second opinion providers is difficult in many regions, such compromising a compensation of different levels of surgery. As a result of our investigation we recommend scientific supervision of currently second opinion procedures and a survey of actual demand from the patient's viewpoint.

Self-supporting V2O5 nanofiber-based electrodes for magnesium-lithium-ion hybrid batteries.

The increasing demand for high energy, sustainable and safer rechargeable electrochemical storage systems for portable devices and electric vehicles can be satisfied by the use of hybrid batteries. Hybrid batteries, such as magnesium-lithium-ion batteries (MLIBs), using a dual-salt electrolyte take advantage of both the fast Li+ intercalation kinetics of lithium-ion batteries (LIBs) and the dendrite-free anode reactions. Here we report the utilization of a binder-free and self-supporting V2O5 nanofiber-based cathode for MLIBs. The V2O5 cathode has a high operating voltage of ∼1.5 V vs. Mg/Mg2+ and achieves storage capacities of up to 386 mA h g-1, accompanied by an energy density of 280 W h kg-1. Additionally, a good cycling stability at 200 mA g-1 over 500 cycles is reached. The structural integrity of the V2O5 cathode is preserved upon cycling. This work demonstrates the suitability of the V2O5 cathode for MLIBs to overcome the limitations of LIBs and MIBs and to meet the future demands of advanced electrochemical storage systems.

Gold nanoparticles phytoreduced with Cornus mas extract mitigate some of gliadin effects on Caco-2 cells.

Celiac disease (CD) is an autoimmune condition that occurs in genetically predisposed people where the ingestion of gluten produces damage in the small intestine. The treatment accepted until now is a strict gluten free diet. This implies the need for novel or adjuvant treatments, in addition to the standard of care. The present study aimed to assess the effect of gold nanoparticles phytosynthesized with Cornus mas extract (AuCM) compared to Cornus mas extract (CM) and luteolin (LT) on Caco-2 cells, exposed or not to gliadin. Ultraviolet-visible spectroscopy and transmission electron microscopy were used for the characterization of AuCM. Measured cellular outcomes included oxidative stress markers (malondialdehyde level, catalase and superoxide dismutase activities), inflammatory response and cellular signaling and transcription factors involved in apoptosis (NFκB, pNFκB, NOS2, TNF-α, TRAIL, Bax, Bcl-2, p53). The internalization of gold nanoparticles in cells was evidenced by transmission electron microscopy (TEM). The gliadin administration induced oxidative stress, improved the activity of antioxidants enzymes, increased NOS2 and NFκB expressions and reduced pNFκB/NFκB ratio. In addition, gliadin enhanced TRAIL and Bcl-2 levels and reduced p53 expression in Caco-2 cells. The pretreatment with AuCM, CM extract and LT diminished oxidative stress and reduced NOS2 activity. AuCM and CM treatment amplified the expression of p53 and pNFκB/NFκB ratio and diminished Bcl-2, NFκB and pNFκB, especially AuCM. The results obtained confirmed that AuCM mitigate some of gliadin effects on Caco-2 cells through modulation of oxidative stress and inflammation.

Laser-induced graphene interdigitated electrodes for label-free or nanolabel-enhanced highly sensitive capacitive aptamer-based biosensors.

Highly porous laser-induced graphene (LIG) is easily generated in complex electrode configurations such as interdigitated electrodes (IDEs). Here, we demonstrate that their superior capacitive response at low frequencies can be exploited in affinity biosensors using thrombin aptamers as model biorecognition elements. Of specific interest was the effect of electrode surface area on capacitance detection, and the comparison between a label-free format and enhancement strategies afforded by carboxy group bearing polymeric nanoparticles or liposomes. Electrochemical impedance spectroscopy (EIS) was used to investigate the LIG performance and optimize the biosensor design. Interestingly, the label-free strategy performed extremely well and additional labels decreased the limit of detection or increased the sensitivity only minimally. It is assumed that the highly porous nature of the LIG structures dominates the capacitive response so that labels removed from the surface have only limited influence Also, while slight performance changes can be observed for smaller vs. larger electrode structures, the performance of a LIG IDE is reasonably independent of its size. In the end, a dynamic range of 5 orders of magnitude was obtained (0.01 nM-1000 nM) with a limit of detection as low as 0.12 pM. When measured in serum, this increased to 1.3 pM. The good reproducibility (relative standard deviation (RSD), 4.90%) and repeatability (RSD, 2.59%) and good long-term stability (>7 weeks at 4 °C) prove that a LIG-based capacitance sensor is an excellent choice for affinity-based biosensor. The ease-of-production, the simplicity of modification and the superior performance even in a label-free format indicate that LIG-based biosensors should be considered in point-of-care diagnostics in the future.