Insecticide susceptibility status of Anopheles gambiae mosquitoes and the effect of pre-exposure to a piperonyl butoxide (PBO) synergist on resistance to deltamethrin in northern Namibia.

BACKGROUND: Pyrethroid-based indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) have been employed as key vector control measures against malaria in Namibia. However, pyrethroid resistance in Anopheles mosquitoes may compromise the efficacy of these interventions. To address this challenge, the World Health Organization (WHO) recommends the use of piperonyl butoxide (PBO) LLINs in areas where pyrethroid resistance is confirmed to be mediated by mixed function oxidase (MFO). METHODS: This study assessed the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to WHO tube bioassays with 4% DDT and 0.05% deltamethrin insecticides. Additionally, the study explored the effect of piperonyl butoxide (PBO) synergist by sequentially exposing mosquitoes to deltamethrin (0.05%) alone, PBO (4%) + deltamethrin (0.05%), and PBO alone. The Anopheles mosquitoes were further identified morphologically and molecularly. RESULTS: The findings revealed that An. gambiae sensu stricto (s.s.) (62%) was more prevalent than Anopheles arabiensis (38%). The WHO tube bioassays confirmed resistance to deltamethrin 0.05% in the Oshikoto, Kunene, and Kavango West regions, with mortality rates of 79, 86, and 67%, respectively. In contrast, An. arabiensis displayed resistance to deltamethrin 0.05% in Oshikoto (82% mortality) and reduced susceptibility in Kavango West (96% mortality). Notably, there was reduced susceptibility to DDT 4% in both An. gambiae s.s. and An. arabiensis from the Kavango West region. Subsequently, a subsample from PBO synergist assays in 2020 demonstrated a high proportion of An. arabiensis in Oshana (84.4%) and Oshikoto (73.6%), and 0.42% of Anopheles quadriannulatus in Oshana. Non-amplifiers were also present (15.2% in Oshana; 26.4% in Oshikoto). Deltamethrin resistance with less than 95% mortality, was consistently observed in An. gambiae s.l. populations across all sites in both 2020 and 2021. Following pre-exposure to the PBO synergist, susceptibility to deltamethrin was fully restored with 100.0% mortality at all sites in 2020 and 2021. CONCLUSIONS: Pyrethroid resistance has been identified in An. gambiae s.s. and An. arabiensis in the Kavango West, Kunene, and Oshikoto regions, indicating potential challenges for pyrethroid-based IRS and LLINs. Consequently, the data highlights the promise of pyrethroid-PBO LLINs in addressing resistance issues in the region.

Volatile-mediated signalling in barley induces metabolic reprogramming and resistance against the biotrophic fungus Blumeria hordei.

Plants have evolved diverse secondary metabolites to counteract biotic stress. Volatile organic compounds (VOCs) are released upon herbivore attack or pathogen infection. Recent studies suggest that VOCs can act as signalling molecules in plant defence and induce resistance in distant organs and neighbouring plants. However, knowledge is lacking on the function of VOCs in biotrophic fungal infection on cereal plants. We analysed VOCs emitted by 13 ± 1-day-old barley plants (Hordeum vulgare L.) after mechanical wounding using passive absorbers and TD-GC/MS. We investigated the effect of pure VOC and complex VOC mixtures released from wounded plants on the barley-powdery mildew interaction by pre-exposure in a dynamic headspace connected to a powdery mildew susceptibility assay. Untargeted metabolomics and lipidomics were applied to investigate metabolic changes in sender and receiver barley plants. Green leaf volatiles (GLVs) dominated the volatile profile of wounded barley plants, with (Z)-3-hexenyl acetate (Z3HAC) as the most abundant compound. Barley volatiles emitted after mechanical wounding enhanced resistance in receiver plants towards fungal infection. We found volatile-mediated modifications of the plant-pathogen interaction in a concentration-dependent manner. Pre-exposure with physiologically relevant concentrations of Z3HAC resulted in induced resistance, suggesting that this GLV is a key player in barley anti-pathogen defence. The complex VOC mixture released from wounded barley and Z3HAC induced e.g. accumulation of chlorophyll, linolenic acid and linolenate-conjugated lipids, as well as defence-related secondary metabolites, such as hordatines in receiving plants. Barley VOCs hence induce a complex physiological response and disease resistance in receiver plants.

Dysregulated energy metabolism impairs chondrocyte function in osteoarthritis.

OBJECTIVES: Metabolic pathways are a series of chemical reactions by which cells take in nutrient substrates for energy and building blocks needed to maintain critical cellular processes. Details of chondrocyte metabolism and how it rewires during the progression of osteoarthritis (OA) are unknown. This research aims to identify what changes in the energy metabolic state occur in OA cartilage. METHODS: Patient matched OA and non-OA cartilage specimens were harvested from total knee replacement patients. Cartilage was first collected for metabolomics, proteomics, and transcriptomics analyses to study global alterations in OA metabolism. We then determined the metabolic routes by tracking [U-13C] isotope with liquid chromatography-mass spectrometry (LC-MS). We further evaluated cellular bioenergetic profiles by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) and investigated the effects of low-dose and short-term effects of 2-deoxyglucose (2DG) on chondrocytes. RESULTS: OA chondrocytes showed increased basal ECAR and more lactate production compared to non-OA chondrocytes. [U-13C] glucose labelling revealed that less glucose-derived carbon entered the tricarboxylic acid (TCA) cycle. On the other hand, mitochondrial respiratory rates were markedly decreased in the OA chondrocytes compared to non-OA chondrocytes. These changes were accompanied by decreased cellular ATP production, mitochondrial membrane potential and disrupted mitochondrial morphology. We further demonstrated in vitro that short-term inhibition of glycolysis suppressed matrix degeneration gene expression in chondrocytes and bovine cartilage explants cultured under inflammatory conditions. CONCLUSION: This study represents the first comprehensive comparative analysis of metabolism in OA chondrocytes and lays the groundwork for therapeutic targeting of metabolism in OA.

Development of a new critical size defect model in the paranasal sinus and first approach for defect reconstruction-An in vivo maxillary bone defect study in sheep.

Fractures of the paranasal sinuses often require surgical intervention. Persisting bone defects lead to permanent visible deformities of the facial contours. Bone substitutes for reconstruction of defects with simultaneous induction of new bone formation are not commercially available for the paranasal sinus. New materials are urgently needed and have to be tested in their future area of application. For this purpose critical size defect models for the paranasal sinus have to be developed. A ≥2.4 cm large bilateral circular defect was created in the anterior wall of the maxillary sinus in six sheep via an extraoral approach. The defect was filled with two types of an osteoconductive titanium scaffold (empty scaffold vs. scaffold filled with a calcium phosphate bone cement paste) or covered with a titanium mesh either. Sheep were euthanized after four months. All animals performed well, no postoperative complications occured. Meshes and scaffolds were safely covered with soft tissue at the end of the study. The initial defect size of ≥2.4 cm only shrunk minimally during the investigation period confirming a critical size defect. No ingrowth of bone into any of the scaffolds was observed. The anterior wall of the maxillary sinus is a region with low complication rate for performing critical size defect experiments in sheep. We recommend this region for experiments with future scaffold materials whose intended use is not only limited to the paranasal sinus, as the defect is challenging even for bone graft substitutes with proven osteoconductivity. Graphical abstract.

A fully ingrowing implant for cranial reconstruction: Results in critical size defects in sheep using 3D-printed titanium scaffold.

Current alloplastic materials such as PMMA, titanium or PEEK don't show relevant bone ingrowth into the implant when used for cranioplasty, ceramic implants have the drawback being brittle. New materials and implant designs are urgently needed being biocompatible, stable enough for cranioplasty and stimulating bone formation. In an in vivo critical size sheep model circular cranial defects (>2.4 cm) were covered with three different types of a 3D-printed porous titanium scaffolds with multidirectional, stochastically distributed architecture (uncoated scaffold, hydroxyapatite-coated scaffold, uncoated scaffold filled with a calcium phosphate bone cement paste containing ß-TCP granules). An empty titanium mesh served as control. Among the different investigated setups the hydroxyapatite-coated scaffolds showed a surprisingly favourable performance. Push-out tests revealed a 2.9 fold higher force needed in the hydroxyapatite-coated scaffolds compared to the mesh group. Mean CT density at five different points inside the scaffold was 2385HU in the hydroxyapatite-coated group compared to 1978HU in the uncoated scaffold at nine months. Average lateral bone ingrowth after four months in the hydroxyapatite-coated scaffold group was up to the implant center, 12.1 mm on average, compared to 2.8 mm in the control group covered with mesh only. These properties make the investigated scaffold with multidirectional, stochastically distributed structure superior to all products currently on the market. The study gives a good idea of what future materials for cranioplasty might look like.

Ecological and geographical speciation in Lucilia bufonivora: The evolution of amphibian obligate parasitism.

Lucilia (Diptera: Calliphoridae) is a genus of blowflies comprised largely of saprophagous and facultative parasites of livestock. Lucilia bufonivora, however, exhibits a unique form of obligate parasitism of amphibians, typically affecting wild hosts. The evolutionary route by which amphibian myiasis arose, however, is not well understood due to the low phylogenetic resolution in existing nuclear DNA phylogenies. Furthermore, the timing of when specificity for amphibian hosts arose in L. bufonivora is also unknown. In addition, this species was recently reported for the first time in North America (Canada) and, to date, no molecular studies have analysed the evolutionary relationships between individuals from Eastern and Western hemispheres. To provide broader insights into the evolution of the amphibian parasitic life history trait and to estimate when the trait first arose, a time-scaled phylogeny was inferred from a concatenated data set comprising mtDNA, nDNA and non-coding rDNA (COX1, per and ITS2 respectively). Specimens from Canada, the UK, Poland, Switzerland, the Netherlands and Germany were analysed, as well as individuals from its sister taxa, the saprophage Lucilia silvarum and a Nearctic species also implicated in amphibian myiasis, Lucilia elongata. Obligate amphibian parasitism appears to have arisen ~4 mya, likely as a result of niche displacement of a saprophagous/facultative parasite ancestor. Consistent paraphyly of L. bufonivora with respect to L. elongata across single-gene phylogenies and high mtDNA genetic distances between Nearctic and Palearctic individuals suggest on-going cryptic speciation facilitated by geographical isolation. These findings suggest that recent reports of L. bufonivora in the Nearctic do not constitute a recent introduction, but instead suggest that it remained unrecorded due to taxonomic confusion and low abundance. This is the first study to confirm the involvement of L. bufonivora in amphibian myiasis in Canada using DNA-based identification methods.

[New options for rehabilitation of conductive hearing loss : Tests on normal-hearing subjects with simulated hearing loss]. / Neue Möglichkeiten der Rehabilitation bei Schallleitungsschwerhörigkeit : Tests an normalhörenden Probanden mit simulierter Schwerhörigkeit.

BACKGROUND: Bone conduction hearing aids can be worn as noninvasive devices using a clip or soft band that exerts pressure on the skin, or they can be surgically implanted. ADHEAR (MED-EL GmbH, Innsbruck, Austria) is a novel noninvasive bone conduction hearing aid that is attached behind the ear using an adhesive adapter and does not exert pressure on the skin. ADHEAR is indicated for patients with conductive hearing loss and normal inner ear function. The aim of this study was to evaluate the achievable hearing improvement with ADHEAR. MATERIALS AND METHODS: Twelve subjects with normal hearing participated in this study. To mimic conductive hearing loss, the participants' ear canals were occluded unilaterally with a foam ear plug. The resultant conductive hearing loss was assessed with pure tone air- and bone-conduction threshold audiometry. Hearing ability was tested with and without ADHEAR via free-field tone audiometry, number perception, and monosyllable perception, with the contralateral ear plugged depending on test requirements. RESULTS: Using ADHEAR, the free-field hearing threshold improved by 13.7 dB at 500 Hz, by 17.9 dB at 1 kHz, by 17.2 dB at 2 kHz, and by 9.8 dB at 4 kHz. In the higher frequencies, a significant pure-tone gain of 14.4 dB at 6 kHz and of 16.5 dB at 8 kHz was observed. Number perception with ADHEAR was mean 69.2% at 35 dB, 97.9% at 50 dB, 100% at 65 dB, and 100% at 80 dB. Monosyllable perception with the ADHEAR was mean 35.0% at 35 dB, 72.3% at 50 dB, 93.5% at 65 dB, and 98.8% at 80 dB. CONCLUSION: Hearing performance was significantly better with ADHEAR under all test conditions except those where maximum perception was already achieved without ADHEAR.

The toad fly Lucilia bufonivora: its evolutionary status and molecular identification.

The blow fly genus Lucilia is composed largely of saprophages and facultative myasis agents, including the economically important species Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) and Lucilia sericata (Meigen). Only one species is generally recognized as an obligate agent of myiasis, Lucilia bufonivora Moniez, and this is an obligate parasite of toads. Lucilia silvarum (Meigen), a sister species, behaves mainly as a carrion breeder; however, it has also been reported as a facultative parasite of amphibians. Morphologically, these species are almost identical, and historically this has led to misidentification, taxonomic ambiguity and a paucity of studies of L. bufonivora. In this study, dipterous larvae were analysed from toad myiasis cases from the U.K., The Netherlands and Switzerland, together with adult specimens of fly species implicated in amphibian parasitism: L. bufonivora, L. silvarum and Lucilia elongata Shannon (from North America). Partial sequences of two genes, cox1 and ef1α, were amplified. Seven additional blow fly species were analysed as outgroups. Bayesian inference trees of cox1, ef1α and a combined-gene dataset were constructed. All larvae isolated from toads were identified as L. bufonivora and no specimens of L. silvarum were implicated in amphibian myiasis. This study confirms L. silvarum and L. bufonivora as distinct sister species and provides unambiguous molecular identification of L. bufonivora.

[Attention deficit-hyperactivity disorder (ADHD) and comorbid mental disorders : ADHD-specific self-rating scales in differential diagnostics]. / Aufmerksamkeitsdefizit­/Hyperaktivitätssyndrom (ADHS) und komorbide psychische Erkrankungen : ADHS-spezifische Selbstbeurteilungsskalen bei der Differenzialdiagnostik.

BACKGROUND: It is still unclear how well the established attention deficit-hyperactive disorder (ADHD)-specific rating scales can differentiate between ADHD symptoms and symptoms of other mental disorders. METHODS: A total of 274 patients with suspected adult ADHD were extensively examined clinically and guideline-conform in an ADHD outpatient clinic. In 190 patients the diagnosis of ADHD could be made with certainty. The patients were also subsequently assessed according to the DSM IV criteria by self-rating scales on current (ADHS-SB, ASRS, CAARS) and retrospective (WURS-K) complaints. A binary logistic regression analysis was performed in order to extract from the questionnaires, which could best distinguish the diagnosis of ADHD from other mental disorders. RESULTS: The results showed that two self-rating scales (WURS-K and ADHS-SB) were sufficient to correctly diagnose ADHD in 83% of the patients examined with a sensitivity of 94% and specificity of 56%. CONCLUSION: The ADHD-specific self-rating scales are additionally useful for the diagnostic differentiation between ADHD-specific and other psychiatric symptoms in the clinical practice and can improve the safety of the diagnosis.

[New clinical applications for laser Doppler vibrometry in otology]. / Neue klinische Anwendungen der Laser-Doppler-Vibrometrie in der Otologie.

BACKGROUND: An instrument to measure vibration in the middle ear needs to be sensitive enough to detect displacement on a nanometer scale, yet not affect the vibration itself. Numerous techniques have been described in the literature, but laser Doppler vibrometry (LDV) has nowadays become established as the standard method in hearing research. OBJECTIVE: This article aims to present possible clinical applications of an LDV system in otology. MATERIALS AND METHODS: A commercially available single-point vibrometer was used. Measurements were carried out both with the sensor head mounted on an operating microscope and as a handheld device with the sensor head manually inserted in the ear canal. For the latter, a custom-made unit containing an electrically tunable lens was attached to the sensor head. Middle ear vibrations were measured in a temporal bone model as well as in patients during and after implantation of a Vibrant Soundbridge (VSB; MED-EL Corp., Durham/NC, USA). RESULTS: Different types of middle ear pathologies can be distinguished by the frequency response of the umbo. The LDV technique can be used for intraoperative quantification of the coupling quality of the VSB's Floating Mass Transducer (FMT; MED-EL) to the ossicle chain during VSB implantation. Postoperatively, the method serves as a follow-up testing tool if a deterioration in aided hearing threshold occurs. The measurement can reveal changes in the umbo transfer function, e. g., due to middle ear scarring or dislocation of the FMT. CONCLUSION: Many clinical questions in otology can be addressed by LDV. However, due to the high acquisition costs of an LDV system, the relatively large instrumental setup, and the large inter-ear variability of middle-ear function, the technique has not (yet) become established in clinical routine.

Insights into psychosis risk from leukocyte microRNA expression.

Dysregulation of immune system functions has been implicated in schizophrenia, suggesting that immune cells may be involved in the development of the disorder. With the goal of a biomarker assay for psychosis risk, we performed small RNA sequencing on RNA isolated from circulating immune cells. We compared baseline microRNA (miRNA) expression for persons who were unaffected (n=27) or who, over a subsequent 2-year period, were at clinical high risk but did not progress to psychosis (n=37), or were at high risk and did progress to psychosis (n=30). A greedy algorithm process led to selection of five miRNAs that when summed with +1 weights distinguished progressed from nonprogressed subjects with an area under the receiver operating characteristic curve of 0.86. Of the five, miR-941 is human-specific with incompletely understood functions, but the other four are prominent in multiple immune system pathways. Three of those four are downregulated in progressed vs. nonprogressed subjects (with weight -1 in a classifier function that increases with risk); all three have also been independently reported as downregulated in monocytes from schizophrenia patients vs. unaffected subjects. Importantly, these findings passed stringent randomization tests that minimized the risk of conclusions arising by chance. Regarding miRNA-miRNA correlations over the three groups, progressed subjects were found to have much weaker miRNA orchestration than nonprogressed or unaffected subjects. If independently verified, the leukocytic miRNA biomarker assay might improve accuracy of psychosis high-risk assessments and eventually help rationalize preventative intervention decisions.

Gastric pH and residual volume after 1 and 2 h fasting time for clear fluids in children†.

INTRODUCTION: Current guidelines suggest a fasting time of 2 h for clear fluids, which is often exceeded in clinical practice, leading to discomfort, dehydration and stressful anaesthesia induction to patients, especially in the paediatric population. Shorter fluid fasting might be a strategy to improve patient comfort but has not been investigated yet. This prospective clinical trial compares gastric pH and residual volume after 1 vs 2 h of preoperative clear fluid fasting. METHODS: Children (1-16 yr, ASA I or II) undergoing elective procedures in general anaesthesia requiring tracheal intubation were randomized into group A with 60 min or B with 120 min preoperative clear fluid fasting. To determine gastric pH and residual volume, the gastric content was sampled in supine, left and right lateral patient position using an oro-gastric tube after intubation. Data are median (interquartile range) for group A or B (P<0.05). RESULTS: In total, 131 children aged 1.01-16.23 yr were included; gastric pH was determined in 120 cases. Patient characteristic data were similar between the two groups, except for gender (46/33 males in group A/B; P=0.02). Despite significantly shorter fasting times for clear fluids in group A compared with group B (76/136 min; P<0.001), no significant difference was observed regarding gastric pH [1.43 (1.30-1.56)/1.44 (1.29-1.68), P=0.66] or residual volume [0.43 (0.21-0.84)/0.46 (0.19-0.78) ml kg(-1), P=0.47]. CONCLUSION: One hour clear fluid fasting does not alter gastric pH or residual volume significantly compared with 2 h fasting. CLINICAL TRIAL REGISTRATION: The study was approved by the local ethics committee (KEK-ZH-Nr. 2011-0034) and registered with ClinicalTrials.gov (NCT01516775).

Total reconstruction of the auricle: our experiences on indications and recent techniques.

INTRODUCTION: Auricular reconstruction is a great challenge in facial plastic surgery. With the advances in surgical techniques and biotechnology, different options are available for consideration. The aim of this paper is to review the knowledge about the various techniques for total auricular reconstruction based on the literature and our experience. METHODS: Approximately 179 articles published from 1980 to 2013 were identified, and 59 articles were included. We have focused on the current status of total auricular reconstruction based on our personal experience and on papers of particular interest, published within the period of review. We have also included a prospective view on the tissue engineering of cartilage. RESULTS: Most surgeons still practice total auricular reconstruction by employing techniques developed by Brent, Nagata, and Firmin with autologous rib cartilage. Within the last years, alloplastic frameworks for reconstruction have become well established. Choosing the reconstruction techniques depends mainly on the surgeon's preference and experience. Prosthetic reconstruction is still reserved for special conditions, even though the material is constantly improving. Tissue engineering has a growing potential for clinical applicability. CONCLUSION: Auricular reconstruction still receives attention of plastic/maxillofacial surgeons and otolaryngologists. Even though clinical applicability lags behind initial expectations, the development of tissue-engineered constructs continues its potential development.

[ENT surgery in patients with anticoagulants and platelet aggregation inhibitors]. / HNO-Operationen bei Patienten mit Gerinnungs- und Thrombozytenaggregationshemmung.

BACKGROUND: Patients with antiplatelet and antithrombotic therapy (AP/AT) represent a substantial proportion of ear, nose and throat (ENT) patients. Despite the ubiquitous consideration of bleeding and ischemic/thrombembolic risk, no detailed assessment of the perioperative setting in an ENT cohort is available in the literature. OBJECTIVES: The goal of the present work is to give a detailed assessment of patients with AP/AT in an ENT cohort resulting in ENT-specific recommendations for daily routine. MATERIALS AND METHODS: In all, 400 randomized patients were asked regarding analgetic therapy in acute pain. Medical data of 5211 patients who underwent head and neck surgery were analyzed for AP/AT therapy. Therapeutic strategies, the perioperative AP/AT therapy, duration of intensive care treatment and hospitalization (ICT/H), application of erythrocytes and internistic/neurolocigal complication data were analyzed in patients with/without AP/AT. RESULTS: Nearly 75 % of our patients were taking AP/AT due to coronary heart disease (CHD), peripheral arterial disease (PAD), cardiac arrhythmia, or cardiovascular disease (CVD). Patients' questionnaire revealed that 31 % of our patients use acetylsalicylic acid in acute pain, which represents 10 % of the overall AP/AT cohort. Head and neck surgery in patients with AP/AT showed an elevated bleeding frequency (p = 0.006) without an elevated risk for internistic/neurological complications. ICT/H were remarkably prolonged (p = 0.006; p = 0.0004). DISCUSSION: Head and neck surgery in patients with AP/AT can be routinely performed. Indication for intensive care, endotracheal intubation, and tracheostomy should be made generously due to high requirements of airway management in ENT. Ischemic/thrombembolic and bleeding risk requires careful assessment in an interdisciplinary setting.

[Complications in 312 cases of nasal and auricular reconstruction via autologous rib cartilage]. / Autologer Rippenknorpel in der Rhino- und Ohrmuschelchirurgie: Komplikationen anhand von 312 Fällen.

BACKGROUND: We present the results and complications with autologous rib cartilage in comparison to other materials in nasal and auricular reconstruction using a large patient collective from our clinic. MATERIAL AND METHODS: The retrospective study included all cases of auricular and nasal reconstruction via rib cartilage between 2001 and 2009. The outcome was analysed by subjective and objective parameters. RESULTS: 51/321 patients underwent plastic reconstructive surgery of the nose, 270/321 received a partial or complete auricle reconstruction with autologous rib cartilage. The complication rate e.g. of hematomas, lesions of the pleura, postoperative pain and keloids at the donation site was small. Concerning the aesthetic results of the nose and auricles 273 of 321 (85%) were satisfied after the first operation. Only 3/51 nasal reconstructions underwent a second operation. In case of complete auricular reconstructions, all patients underwent at least 2 operations for the three-dimensional look. CONCLUSIONS: The use of autologous rip cartilage is still a good option in the auricular and nasal reconstruction. Depending on the expertise of the surgeon the postoperative aesthetic results are good with a low complication rate. However concerning the bigger effort in several aspects for the surgeon as the patient it should be reserved to specific indication criterias.

Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons.

BACKGROUND: Beneficial effects of ginger in the treatment of gastrointestinal (GI) problems and chemotherapy-induced nausea and vomiting are well accepted. In rodents, the action of ginger seems to be mediated by the inhibition of 5-HT3 receptors, which are established targets to combat emesis and irritable bowel syndrome. METHODS: Heterologously expressed human 5-HT3 A or 5-HT3 AB receptors were characterized by means of Ca(2+) influx studies using HEK293 cells. Complementing Ca(2+) measurements in Fluo-4-AM-stained whole-mount preparations of the human submucous plexus were carried out. Furthermore, [3H]GR65630 binding assays were performed to reveal the mode of action of ginger and its pungent compounds. KEY RESULTS: We show for the first time that ginger extracts and its pungent arylalkane constituents concentration-dependently inhibit activation of human 5-HT3 receptors. Ginger extracts inhibited both receptors with increasing content of pungent compounds, confirming that these are part of ginger's active principle. Inhibition potencies of the arylalkanes 6-gingerol and 6-shogaol on both receptors were in the low micromolar range. A lipophilic ginger extract and 6-gingerol had no influence on 5-HT potency, but reduced the 5-HT maximum effect, indicating non-competitive inhibition. The non-competitive action was confirmed by [(3) H]GR65630 binding, showing that the ginger extract did not displace the radioligand from 5-HT3 A and 5-HT3 AB receptors. The potential relevance of the inhibitory action of ginger on native 5-HT3 receptors in the gut was confirmed in whole-mount preparations of the human submucous plexus. While a general neurotoxic effect of 6-gingerol was ruled out, it inhibited the 2-methyl-5-HT-mediated activation of 5-HT3 receptors residing on enteric neurons. CONCLUSIONS & INFERENCES: Our findings may encourage the use of ginger extracts to alleviate nausea in cancer patients receiving chemotherapy and to treat functional GI disorders.

[Management of impacted foreign bodies in the upper gastrointestinal tract in adult patients - results of a retrospective case series]. / Management von impaktierten Fremdkörpern im oberen Gastrointestinaltrakt bei erwachsenen Patienten - Ergebnisse einer retrospektiven Fallserie.

INTRODUCTION: Impaction of foreign bodies in the upper gastrointestinal tract represents a rare endoscopic emergency regarding the danger of organic lesions. Therefore, the therapeutic strategy, rational postinterventional monitoring and potential consequences for the course in the future are often not clear. METHODS: Out of all oesophagogastroduodenoscopies performed between 2008 and 2010 (n = 10,830), the endoscopies due to bolus impaction were analysed retrospectively concerning endoscopic findings, course of intervention and causative predisposing factors using descriptive statistics. RESULTS: In the study period, endoscopy was performed in 45 different patients 49 times when foreign body impaction was suspected. In 38 cases (77.6%) a foreign body could be detected by endoscopy, most frequently a meat bolus (65.8%), followed by dental prostheses and tablets. Endoscopic removal could be successfully performed in 97.4%. An operation was necessary in only one patient. A macroscopically unremarkable upper gastrointestinal tract without any predisposing conditions for foreign body impaction could be detected in 33.3%. In one case eosinophilic oesophagitis could be diagnosed histologically. The foreign body was pushed into the stomach by the "push technique" in 54.1%. The foreign body removal was performed as an ambulant intervention in 63.2%. DISCUSSION: In the majority of cases, impacted foreign bodies of the upper gastrointestinal tract could be removed safely by endoscopy, e.g., using the "push technique". However, the therapeutic strategy should be individually adjusted based on the consistancy of the foreign body. If no predisposing conditions can be found, histological diagnosis should be performed to detect potential eosinophilic oesophagitis early enough.

[The application of implantable hearing aids using the Vibrant Soundbridge as an example]. / Einsatz implantierbarer Hörgeräte am Beispiel der Vibrant Soundbridge.

Over the last decade, bone conducting hearing aids, cochlear implants and implantable hearing aids have come to represent additional treatment options in clinical routine-alongside conventional hearing aids-for hearing impaired patients. Thanks to experience gained in recent years with implantable hearing aids and the consistent evaluation of functional results, the original spectrum of indications has been progressively extended. Today, implantable hearing aids are available for the hearing (re)habilitation of various forms of middle ear pathology as well as sensorineural hearing loss within the audiological criteria. With CE certification for children, the treatment of younger patients with implantable hearing aids has also become possible. Using the Vibrant Soundbridge as an example, the function, indications and contraindications of implantable hearing aids are described and the surgical procedure and post-operative care discussed.

[Principles of cholesteatoma surgery]. / Prinzipien der sanierenden Cholesteatomchirurgie.

As a potentially life-threatening disease, cholesteatoma of the petrous bone generally requires a surgical approach. Surgery aims to produce an ear that is easy to care for and is free of recurrent or residual cholesteatoma. Hearing improvement is of secondary importance. Nevertheless the sound conduction system is generally reconstructed as a single-stage procedure. There are various possible methods of dealing with a cholesteatoma: (i) preserving or reconstructing the posterior meatal wall with an aerated mastoid (closed technique) or obliteration of the mastoid completely or partially after removal of the posterior wall (closed technique); and (ii) leaving the cavity open for inspection (open technique). In our opinion any technique where the mastoid is not open for inspection should be called a closed technique. Both techniques have their specific advantages and disadvantages.

[Cochlear implantation: a changing indication]. / Cochleaimplantatversorgung: Indikation im Wandel.

In recent years the indication criteria for cochlear implantation (CI) have changed. To gain optimal benefits, early implantation in prelingually deaf children is necessary. Even additional disabilities are no longer contraindications for CI. Nowadays the criteria for implantation not only include deafness but also residual hearing. Combined electric-acoustic stimulation has been established as a treatment option in patients with hearing still functioning in the low frequencies. Due to the benefits of binaural hearing, bilateral CI has become standard over the last decade. Recent experience has shown the benefits of CI in unilateral deafness and in cases of severe tinnitus. The actual benefit of CI shows great inter-individual differences. We usually expect (re-)habilitation of language communication skills with implantation.