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.

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.

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.

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.

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.

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.

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

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.

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.

Flemish population data and sequence structure of the hypervariable tetranucleotide repeat locus D12S1090.

The allele frequency and sequence structure of the STR locus D12S1090 were investigated in 598 Flemish individuals. The locus shows a complex organisation with repetitions of GATA interrupted by TA and other tetra- and pentanucleotide blocks. No deviation from Hardy-Weinberg equilibrium was observed. The extensive polymorphism makes it a powerful tool for identity as well as paternity testing and even permits differentiation of closely related populations, such as Flemish and Germans. D12S1090 seems to be one of the most informative STRs, however, as seen in other highly variable STRs, the observed mutation frequency of 5.1 x 10(-3), is relatively high. of STR loci is typing highly polymorphic STRs such as ACTBP2 [3]. We thus investigated the tetranucleotide (GATA) repeat locus D12S1090 (GDB accession number GDB:376560, also known as GATA5A09) in a population sample from Flanders, the Dutch speaking part of Belgium. Although this STR is considered to be highly polymorphic [4], compared with other STRs, it has only scarcely been studied.

Variations in primer sequences are the origin of allele drop-out at loci D13S317 and CD4.

STRs have become almost the exclusive tool of genetic scientists in forensic typing work. Consequently, large numbers of samples are genotyped and the detection of rare abnormalities is to be expected. We found rare losses of alleles, also known as drop-out, at the two STR loci D13S317 and CD4. Drop-out at D13S317 was accidentally found in typing of suspects in a murder case and three other examples of drop-out were found at locus CD4 during paternity testing. The lost alleles reappeared when alternative PCR primer pairs were used. Sequences of lost alleles were characterised at the molecular level after cloning. Variations were found in the primer sequences and these are believed to prevent amplification or to reduce amplification yield and to be the origin of the allele drop-out.

Mutation of the repeat number of the HPRTB locus and structure of rare intermediate alleles.

During routine paternity testing a mutation of a paternal allele at the HPRTB locus was observed. The opportunity was taken to analyse this mutation at a molecular level. The repeat sequence is flanked by an imperfect repeat sequence and this region could be involved in the mutation mechanism. For this reason, we also examined the structure of "intermediate" alleles. Sequencing confirmed the insertion of a perfect repeat motif and revealed a deletion of a dinucleotide some 50 nucleotides downstream from the repeat sequence for the intermediate alleles. It is likely that these intermediate alleles are rare biallelic deletion polymorphisms and are probably not involved in the mutation or variation mechanism of this locus.

The evolution of platelet procoagulant activity of remnant platelets in stored platelet concentrates prepared by the platelet-rich plasma method and the buffy coat method.

Platelets stored as concentrates are gradually activated (storage lesion), a process associated with changes in the expression of platelet procoagulant activity (PPCA). The aim of the present study was to evaluate the evolution of PPCA and the mean platelet volume (MPV) of stored platelets prepared according to the platelet-rich method (PRM) and the buffy coat method (BCM). Using the platelet factor 3 availability clotting test (PF3AT) on appropriately diluted concentrate samples, we found a decrease in PPCA expression of remnant platelets as a function of storage time (0.025 < p < 0.01 between day 1 and 7) in PRM-derived but not in BCM-derived platelet concentrates. Using the PF3AT reduction test we found a more important clotting time reduction in samples obtained from BCM than in samples obtained from PRM platelet concentrates, suggesting a higher PPCA expression of BCM platelets, not significant after 1 day but highly significant after 3 days (p < 0.0005) and after 7 days (p < 0.0005) of storage, as compared with PRM platelets. For both PRM and BCM concentrates there were no significant MPV changes as a function of storage time, but at any storage day the MPV of BCM concentrates was significantly higher (p < 0.0005) than the MPV of PRM concentrates. We conclude that the decrease of PPCA expression in PRM-derived concentrates as a function of storage time is in agreement with the gradual decrease of the platelet activation status in PRM concentrates during storage. There are probably several factors or variables causing platelets of BCM concentrates to express higher PPCA than those of PRM concentrates. Higher PPCA expression in BCM concentrates may be explained by an intrinsic platelet property, such as a difference in MPV between the two kinds of concentrates, or it may be related to an extrinsic factor such as different storage media, e.g., undiluted autologous plasma in PRM concentrates versus Plasmalyte A-diluted autologous plasma in BCM concentrates. Whether the difference in PPCA expression of remnant platelets in PRM and BCM concentrates is just an in vitro laboratory finding or may have consequences for the therapeutic efficiency of the concentrates is an interesting, still unresolved question.

Histamine synthesis by white cells during storage of platelet concentrates.

OBJECTIVES: To resolve the question whether histamine, like some cytokines, is actively synthesized during storage of platelet concentrates. METHODS: We prepared conventional buffy coat platelet concentrates and stored them in the usual way at 22 degrees C. Disodium cromoglycate was added to one series, saline to the controls. Samples were taken at intervals, to be tested for histamine and interleukin-6 (IL-6). RESULTS: The plasma histamine level increased from a median of 1.02 ng/ml (range 0.11-3.27) to 12.9 ng/ml (range 4.30-32.9) whereas the total histamine content of the platelet concentrates remained unchanged during the 5-day storage period. In contrast, the total content of IL-6 increased rapidly. CONCLUSION: Histamine is not synthesized during storage of platelets, whereas IL-6 is. The addition of disodium cromoglycate, a substance that inhibits granulocyte activation, had no effect on the release of histamine or on the total histamine content at various storage times.