Prospective case-controlled sound localisation study after cochlear implantation in adults with single-sided deafness and ipsilateral tinnitus.

OBJECTIVES: To analyse the sound localisation skills of subjects with profound single-sided deafness (SSD) and accompanied ipsilateral tinnitus who are using a cochlear implant (CI) for between 4 and 11 years. DESIGN: Sound localisation skills were tested using nine loudspeakers in a frontal semicircle ranging from -90° to +90°. Subjects were tested in the CION and the CIOFF conditions via 3 localisation stimuli: broadband noise (BB), low-pass noise (LP) and high-pass noise (HP). PARTICIPANTS: The test group consisted of 10 adult subjects with profound sensorineural SSD, ipsilateral tinnitus and a CI. Normative data of a control group of 30 normal hearing subjects were used for comparison. MAIN OUTCOME MEASURES: Sound location accuracy was analysed via the root-mean-square error (RMSE), the mean absolute error (MAE), the localisation bias ('b') and the bias-adjusted deviation ('db '). Subjective dynamic aspects of hearing were assessed via a reduced version of the Speech, Spatial and Qualities of Hearing Scale (SSQ5 ). RESULTS: For all 3 stimuli, the RMSE improved significantly in SSD subjects in the CION condition compared to the CIOFF condition. The localisation accuracy of subjects with SSD improved significantly for BB and HP stimuli. A significant bias-adjusted deviation 'db ' was found for the BB and HP stimuli. Subjects' mean SSQ5 scores were significantly higher in the CION condition at test date than in the CIOFF condition preoperatively. CONCLUSIONS: Subjects can better locate sound in the CION condition than in the CIOFF condition.

Study of composition change and agglomeration of flue gas cleaning residue from a fluidized bed waste incinerator.

Blocking of the collection hoppers of the baghouse filters in a fluidized bed incinerator for co-incineration of high calorific industrial solid waste and sludge was observed. The composition of the flue gas cleaning residue (FGCR), both from a blocked hopper and from a normal hopper, was investigated by (differential) thermogravimetric analysis, quantitative X-ray powder diffraction and wet chemical analysis. The lower elemental carbon concentration and the higher calcium carbonate concentration of the agglomerated sample was the result of oxidation of carbon and subsequent reaction of CO2 with CaO. The evolved heat causes a temperature increase, with the decomposition of CaOHCl as a consequence. The formation of calcite and calcium chloride and the evolution of heat caused agglomeration of the FGCR. Activated lignite coke was replaced by another adsorption agent with less carbon, so the auto-ignition temperature increased; since then no further block formation has occurred.

Prediction of the Cochlear Implant Electrode Insertion Depth: Clinical Applicability of two Analytical Cochlear Models.

Although the spiral anatomy of the human cochlea seems evident, measuring the highly inter-variable true dimensions is still challenging. Today, only a few three-dimensional reconstruction models of the inner ear are available. Previously, spiral equations were applied to two-dimensional computed tomography (CT) images to predict the electrode insertion depth prior to cochlear implantation. The study aimed primarily to compare the clinical applicability of two analytical cochlear models using a recently introduced planning software to predict the insertion depth of the electrode array of 46 cochlear implant recipients. One was based upon the Escudé formula, which relies only on the basal turn diameter, and another based upon the Elliptic-Circular Approximation (ECA), using the diameter and width. Each case was measured twice by two ENT surgeons. Secondly, in order to measure the benefit of the new planning software over the use of the existing clinical routine method, the results were compared to the prediction based upon a two-dimensional CT image. The intra -and inter-observer agreement using the planning software was significantly better when the ECA was applied, compared to the Escudé formula (p < 0.01). As a reference, the predicted insertion depth was compared to the actual insertion depth measured on post-operative images. The mean absolute error was |2.36| (|1.11|) mm in case of the Escudé approach and |1.19| (|0.92|) mm in case of the ECA. The use of a new planning software that allows three-dimensional handling, integrating the diameter and width of the basal turn (ECA formula), resulted in the most accurate predictions of the electrode insertion depths.

Heparan sulfate expression in polarized epithelial cells: the apical sorting of glypican (GPI-anchored proteoglycan) is inversely related to its heparan sulfate content.

Several processes that occur in the luminal compartments of the tissues are modulated by heparin-like polysaccharides. To identify proteins responsible for the expression of heparan sulfate at the apex of polarized cells, we investigated the polarity of the expression of the cell surface heparan sulfate proteoglycans in CaCo-2 cells. Domain-specific biotinylation of the apical and basolateral membranes of these cells identified glypican, a GPI-linked heparan sulfate proteoglycan, as the major source of apical heparan sulfate. Yet, most of this proteoglycan was expressed at the basolateral surface, an unexpected finding for a glypiated protein. Metabolic labeling and chase experiments indicated that sorting mechanisms, rather than differential turnover, accounted for this bipolar expression of glypican. Chlorate treatment did not affect the polarity of the expression of glypican in CaCo-2 cells, and transfectant MDCK cells expressed wild-type glypican and a syndecan-4/glypican chimera also in an essentially unpolarized fashion. Yet, complete removal of the heparan sulfate glycanation sites from the glypican core protein resulted in the nearly exclusive apical targeting of glypican in the transfectants, whereas two- and one-chain mutant forms had intermediate distributions. These results indicate that glypican accounts for the expression of apical heparan sulfate, but that glycanation of the core protein antagonizes the activity of the apical sorting signal conveyed by the GPI anchor of this proteoglycan. A possible implication of these findings is that heparan sulfate glycanation may be a determinant of the subcellular expression of glypican. Alternatively, inverse glycanation-apical sorting relationships in glypican may insure near constant deliveries of HS to the apical compartment, or "active" GPI-mediated entry of heparan sulfate into apical membrane compartments may require the overriding of this antagonizing effect of the heparan sulfate chains.

Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.

BACKGROUND AND AIMS: Cold snare polypectomy (CSP) is an accepted technique to remove diminutive or small (6-9 mm) polyps. Here we present a series of CSP for advanced non-pedunculated polyps (> 10 mm). PATIENTS AND METHODS: This is a retrospective, single operator study. A total of 111 patients with non-pedunculated polyps (Paris classification 0-IIa, 0-IIb, 0-Is) estimated > 10 mm, underwent CSP. RESULTS: A total of 129 polyps were removed (87 0-IIa, 18 0-IIb, 24 0-Is). The number of these polyps ranked according to size were as follows : 11-19 mm : 63 (49%), 20-29 mm : 44 (34%), > 30 mm : 22 (17%). Thirty-eight (29.5%) were sessile serrated adenomas, 47 (36%) were tubular adenomas, 25 (19.3%) were villous adenoma's and 18 (14%) were hyperplastic polyps. Forty-nine (38%) polyps were resected in a piecemeal fashion, submucosal injection with diluted Indigo Carmine was used in 24 (19%). Immediate oozing bleeding was frequent but in almost all patients rapid spontaneous haemostasis occurred. In only one patient haemostatic clipping was required (in order to achieve hemostasis). Preventive clipping was used in 3 patients. There were no complications. Seventy-two patients (with 87 lesions) had a follow-up colonoscopy. Of these 87 lesions, 9 had residual adenomatous tissue (10.3 %). According to the size of the original polyp, the distribution was as follows: 11-19 mm : 2/36 (5.5 %), 20-29 mm : 4/32 (12.5 %), > 30 mm : 3/19 (15.7%). CONCLUSION: CSP for advanced, non-pedunculated lesions is feasible, effective and extremely safe.

Sequential dual-site High-Definition transcranial Direct Current Stimulation (HD-tDCS) treatment in chronic subjective tinnitus: study protocol of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Chronic tinnitus is a highly prevalent symptom, with many patients reporting considerable effects of tinnitus on quality of life. No clear evidence-based treatment options are currently available. While counseling-based methods are valuable in some cases, they are not sufficiently effective for all tinnitus patients. Neuromodulation techniques such as high-definition transcranial direct current stimulation (HD-tDCS) are proposed to have positive effects on tinnitus severity but, to date, these effects have not been proven conclusively. The proposed trial will investigate the hypothesis that chronic tinnitus patients receiving HD-tDCS will report a positive effect on the impact of tinnitus on daily life, as compared to patients receiving sham stimulation. METHODS: This study proposes a randomized, double-blind, placebo-controlled trial with parallel group design. A total of 100 chronic tinnitus patients will be randomly allocated to an experimental group or a sham group, with allocation stratified according to gender and tinnitus severity. Patient and researcher will be blinded to the patient's allocation. Patients will undergo six sessions of sequential dual-site HD-tDCS of the left temporal area and the right dorsolateral prefrontal cortex. Evaluations will take place at baseline, immediately following treatment, and at three and six months after the start of the therapy. The primary outcome measure is the change in Tinnitus Functional Index (TFI) score. Secondary outcome measures include audiological measurements, cortical auditory evoked potentials, the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for hearing-impaired individuals (RBANS-H), and supplementary questionnaires probing tinnitus severity and additional symptoms. By use of a linear regression model, the effects of HD-tDCS compared to sham stimulation will be assessed. DISCUSSION: The objective of this study is to evaluate whether HD-tDCS can reduce the impact of tinnitus on daily life in chronic tinnitus patients. To date, published trials on the effects of HD-tDCS on tinnitus suffer from a lack of standardization and few randomized controlled trials exist. The proposed study will be the first adequately powered trial to investigate the effects of sequential dual-site HD-tDCS on tinnitus severity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03754127 . Registered on 22 November 2018.

mRNA-electroporated mature dendritic cells retain transgene expression, phenotypical properties and stimulatory capacity after cryopreservation.

Genetically modified dendritic cells (DC) are increasingly used in vitro to activate cytotoxic T lymphocyte (CTL) immune responses. Because T cell activation protocols consist of multiple restimulation cycles of peripheral blood lymphocytes with antigen-loaded mature DC, continuous generation of DC is needed throughout the experiment. Therefore, cryopreservation of DC loaded with antigen is a valuable alternative for weekly generation and modification of DC. Recently, we described an antigen loading method for DC based on electroporation of defined tumor antigen mRNA. In this study, we demonstrate that mRNA-electroporated DC can efficiently be prepared for cryopreservation. Using an optimized maturation and freezing protocol after mRNA electroporation, we obtained high transgene-expressing viable mature DC. In addition, we showed that these modified cryopreserved DC retain stimulatory capacity in an influenza model system. Therefore, cryopreservation of mature mRNA-electroporated DC is a useful method for continuous availability of antigen-loaded DC throughout T cell activation experiments.

Heparan sulfate proteoglycans. Essential co-factors in receptor-mediated processes with relevance to the biology of the vascular wall.

Heparan sulfate (HS), a mixed bag of complex, heterogeneous and highly charged polysaccharides, is an essential co-factor in a large number of receptor-ligand interactions and cellular pathways. These co-factor functions depend on the binding-interactions of the HS chains with the ligand or receptor, or both. These binding interactions and the ensuing functional effects often depend on defined carbohydrate sequences within the HS chains, whereby the required sequences are not always represented within all natural forms of the polysaccharide. The proteins that are substituted with HS resort from a limited number of protein families, with different cellular, subcellular and supramolecular associations, and show differential activities in functional assays. It is likely that the natural co-factor functions of the HS proteoglycans depend on glycan-protein and protein-protein interactions that are subject to modulation, both at the glycan and protein levels.

Detection of herpes simplex virus in the cerebrospinal fluid of patients with encephalitis using the polymerase chain reaction.

Herpes simplex encephalitis is a neurologic emergency demanding immediate institution of specific therapy in order to prevent mortality. Diagnosis, however, is a complex matter with controversy existing over the appropriateness of brain biopsy. We report the demonstration of herpes simplex virus DNA by means of the polymerase chain reaction (PRC) in the cerebrospinal fluid of 3 patients with herpes simplex encephalitis. One of the patients suffered from brain-stem encephalitis with high intensity signals in the pons on magnetic resonance imaging, the second reported case of this entity. The PCR for herpes simplex on a control series of cerebrospinal fluid of 20 patients with other central nervous system infections was negative. PCR of cerebrospinal fluid offers a sensitive, specific and rapid diagnosis of herpes simplex encephalitis, making brain biopsy unnecessary. Still, the importance of strict measures to prevent contamination cannot be stressed enough. It is possible that due to the high sensitivity of the PCR, herpes simplex may be found in other infectious syndromes of the central nervous system.

Estradiol, testosterone, dehydroepiandrosterone and androstenedione: novel derivatives and enantiomers. Interactions with rat liver microsomal cytochrome P450 and antioxidant/radical scavenger activities in vitro.

Interactions of 27 steroids, among them 17 derivatives such as ethers, sulfates and amidosulfonates derived from 17 beta- and 17 alpha-estradiol, from testosterone and alpha- and beta-dihydrotesosterone and from dehydroepiandrosterone with rat liver microsomal cytochromes P450 (P450) were investigated in vitro by assessing binding to P450 and effects on P450 mediated monooxygenase functions as measured by different model reactions: ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD) and ethylmorphine N-demethylation (EMND). With the exception of 17 alpha-estradiol-3-dimethylamidosulfonate, estrone, its -3-methylether and -3-amidosulfonate and testosterone, all other steroids displayed type I or reverse type I binding to P450. All steroids inhibited EROD activity in micromolar concentrations. An additional strong inhibition of ECOD and EMND activities was only demonstrated for the androgens and progestins. Estriol, estrone and mestranol displayed less inhibitory actions on the model reactions than estradiol. No major differences in comparison to the parent compounds were noted with the other derivatives. The only exceptions were 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol, which displayed stronger effects than estradiol, and dehydroepiandrosterone-3-sulfate, which was less effective than dehydroepiandrosterone. Possible antioxidant properties of the steroids were examined by the stimulated lipid peroxidation (LPO), H2O2 production, and lucigenin (LC) and luminol (LM) amplified chemiluminescence (CL) using rat liver microsomes. Additionally, the influence on rat whole blood chemiluminescence (WB-CL) was assessed. All the estrogens, but not their methylethers and amidosulfonates inhibited LPO in micromolar concentrations. The effects on the other oxidase model reactions or on WB-CL were less distinct. Only ethinylestradiol and 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol displayed a strong inhibitory action on all model reactions. With the exception of dehydroepiandrosterone-3-sulfate, which in general had only weak effects, the androgen and progestin derivatives, in contrast, strongly decreased H2O2 formation and LM- and LC-CL, but were mostly ineffective on LPO and WB-CL.

[The potentials and limits of percutaneous needle biopsy in the histological classification of malignant tumors]. / Möglichkeiten und Grenzen der perkutanen Nadelbiopsie in der histologischen Klassifikation von malignen Tumoren.

180 sonographically guided percutaneous biopsies in a variety of anatomic regions (abdomen, 110; thorax, 33; neck, 28; breast, 4; extremity, 5) were retrospectively reviewed to evaluate the percentage of correct histologic diagnoses of malignant tumours. A positive diagnosis of malignancy was established in 101 (96%) of 107 malignant tumours. A correct histologic classification was achieved in 79 (73%) of 108 malignant tumours by means of cytologic and histologic examination of the tissue acquired. Correct histologic classification of malignant tumours depends on several factors including a) needle diameter, b) location of the tumour, c) clinical constellation and, most important d) the complexion of the tumour histology. The percentage of correct histological diagnoses varied between carcinomas (79%), Hodgkin lymphomas (100%), non-Hodgkin lymphomas (45%), sarcomas (50%) and carcinoid tumours (0%). Histological classification of malignant tumours by means of percutaneous biopsy can be improved by multiple biopsies of different portions of the tumour and by using larger cutting needles.

[Pulmonary embolism: which diagnostic approach?]. / L'embolie pulmonaire: quelle démarche diagnostique?

The recent literature dealing with the diagnosis of pulmonary embolism is reviewed. Clinical signs, electrocardiogram and arterial blood gases analysis are not very helpful whereas a normal level of blood D-dimers makes the diagnosis of pulmonary embolism very unlikely. Lung scanning must be interpreted carefully in parallel with chest radiography. It is most useful if the pattern is either normal or of high probability. All intermediate scans are inconclusive and need a pulmonary arteriogram. Another option in patients with good cardiorespiratory reserve is the use of repeated non-invasive investigations of the lower limbs.

Towards a consensus on a hearing preservation classification system.

CONCLUSION: The comprehensive Hearing Preservation classification system presented in this paper is suitable for use for all cochlear implant users with measurable pre-operative residual hearing. If adopted as a universal reporting standard, as it was designed to be, it should prove highly beneficial by enabling future studies to quickly and easily compare the results of previous studies and meta-analyze their data. OBJECTIVES: To develop a comprehensive Hearing Preservation classification system suitable for use for all cochlear implant users with measurable pre-operative residual hearing. METHODS: The HEARRING group discussed and reviewed a number of different propositions of a HP classification systems and reviewed critical appraisals to develop a qualitative system in accordance with the prerequisites. RESULTS: The Hearing Preservation Classification System proposed herein fulfills the following necessary criteria: 1) classification is independent from users' initial hearing, 2) it is appropriate for all cochlear implant users with measurable pre-operative residual hearing, 3) it covers the whole range of pure tone average from 0 to 120 dB; 4) it is easy to use and easy to understand.

Evolution, health and disease--Darwinian approaches to medicine.

It is widely recognized that the evolution theory has contributed to understanding genetics and infectious disease. More generally, however, training in evolutionary thinking can help both biomedical researchers and clinicians in asking useful questions they might not come up with otherwise. In this paper, evolutionary insights with clinical applications are discussed on allergy and cancer, the causes of atherosclerosis, antibiotic use and resistance, the polymorphic Major Histocompatibility Complex, the bubonic plague bottleneck and symptoms versus disease. Those examples make a strong case for recognizing evolution biology as a basic science for medicine.

The ethical debate on present day paternity testing practices.

The last years, the number of paternity tests on buccal swabs sold over the internet as "test kits", has steeply increased. The commercial providers of these services facilitate controversial practices, including clandestine sampling at home, anonymous sending off for analysis, motherless testing and using "stolen" personal objects containing biological material (combs, cigarette butts). This has led to concern on the consequences on the family unit--especially the child--which may suffer emotionally, physically and financially. In reaction, legal initiatives are appearing throughout Europe. The UK Human Genetics Commission has advised that the non-consensual obtaining and analysis of personal genetic information should be a new criminal offence. The German Federal Court of Justice has ruled that paternity tests performed without the mother's knowledge are inadmissible as evidence in lawsuits. French law strictly forbids the application of DNA testing without the involvement of the court system. In Belgium, a proposal for law has been laid down where the offering to