Aims
The frequency of the use of intratympanic steroids (ITS) as a treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) in Europe is still unknown and remains a contentious issue ...amongst otolaryngologists. We undertook a survey of otolaryngologists in Germany and Austria to establish if there is any professional consensus with which to form a protocol for its use.
Methods
A survey of 21 questions was distributed electronically to otolaryngologists in Germany and Austria and data on demographics, indications for intratympanic treatment, procedure, follow-up, and outcomes were analysed.
Results
We received 908 responses. 49.1% of otolaryngologists used ITS for ISSNHL. Of those otolaryngologists who use ITS, 73.7% do not use it as primary treatment. 20.6% use ITS in conjunction with oral steroids for primary treatment and only 5.8% use ITS as monotherapy for primary treatment. 90.5% use ITS as salvage therapy. 81.1% do not consider the use of ITS after 2 weeks from the onset of symptoms. 8.3% used a tympanostomy tube and while the most commonly used steroid was dexamethasone at a concentration of 4 mg/ml (61%), a wide variety or other steroids and concentrations were used.
Conclusions
This survey illustrates wide variation of current practice of intratympanic corticosteroid injection for ISSHL in Germany and Austria. In the absence of high-level evidence, knowing what current practice is allows clinicians to assess what they do against what their colleagues are doing, and if they do something very different, make them question their practice. Moreover, the obtained data will help to direct future clinical trials with the aim to compare the outcomes of more commonly used protocols.
The ATP binding cassette (ABC) transporter molecule ABCA1 participates in the cholesterol transport within and through cell membranes. We recently demonstrated that in dog spermatozoa, capacitation ...could be decreased with probucol (PRO), an ABCA1 specific antagonist. In this study, a dose-effect relationship of PRO on dog sperm capacitation, tyrosine phosphorylation and cholesterol efflux from the sperm plasma membrane was investigated. A total of 16 ejaculates from dogs of different breeds, aged 2–4 years were used. Sperm motility and membrane integrity in the main fraction was determined by CASA. Samples were stained with a boron dipyrromethene difluoride (BODIPY) fluorophore (P9672, Sigma- Aldrich, A) diluted in DMSO at a final concentration of 0.4 μM. All samples were divided into 5 aliquots, with 0, 100, 250, 500 and 1000 μM of PRO. After incubation at 37 °C for 2 h, PI was added and flow cytometry performed. All aliquots were examined for capacitation and acrosome reaction by using the CTC assay and tyrosine phosphorylation (TP). Membrane integrity was measured in all aliquots to investigate the effect of PRO on cell membranes. Membrane integrity did not differ between controls (0 μM), and 100, 250 and 500 μM PRO, but decreased with 1000 μM PRO (p < 0.05). Increasing PRO concentration decreased the percentage alive cells with cholesterol efflux per PRO group (0 μM: 77.8 ± 10.6%, 100 μM: 63.7 ± 11.7%, 250 μM: 52.1 ± 12.9%, 500 μM: 37.7 ± 11.6%, 1000 μM: 33.1 ± 14.4%; p < 0.05), decreased head and entire tail phosphorylated cells (0 μM: 34.6%, 1000 μM: 5.1% p < 0.05); and decreased the percentage capacitated cells (maximum with PRO 500 μM: capacitated vs. control: 54.2 ± 17% vs 25 ± 7.7%, p < 0.05). Conclusion: PRO decreased the cholesterol efflux, and decreased tyrosine phosphorylation and capacitation in a dose-dependent manner. This suggests a strong involvement of the ABCA1 transporter in different functional aspects of sperm capacitation in dogs.
•Probucol is an ABCA1 specific antagonist and effective in dog spermatozoa membranes.•Increasing probucol decreased the percentage alive cells with cholesterol efflux.•Increasing probucol decreased head and entire tail phosphorylated cells.•Increasing probucol decreased the percentage capacitated cells.•The ABCA1 transporter is involved in sperm capacitation in dogs.
Background One-third of the world's population is infected with the dormant tuberculosis bacillus, and there have been no new antimycobacterial compounds with new modes of action for over 30 years. ...Extensively drug-resistant tuberculosis is resistant to first- and second-line drugs, which can have severe side effects, and requires the breakthrough of new antituberculotics and resistance-modifying agents. Efflux pumps can cause multidrug resistance and have recently evoked much interest as promising new targets in antimicrobial therapy. Objectives The study was performed to set up an ethidium bromide (EtBr) efflux assay in Mycobacterium smegmatis mc2155 for testing plant natural compounds as mycobacterial efflux pump inhibitors (EPIs). Methods After determining the MICs of the putative EPIs, they were tested for synergistic effects with EtBr prior to the efflux assay. Results We established an EtBr efflux assay in M. smegmatis mc2155. The isoflavone biochanin A exhibited efflux pump inhibiting activity comparable to that of verapamil. The flavone luteolin and the stilbene resveratrol were less active. Conclusions A new assay was established to observe the EtBr efflux in M. smegmatis and was applied to evaluate plant phenolic compounds. Our results highlighted that the isoflavonoid biochanin A exhibited better EPI activities than other flavonoids in mycobacteria.
Background: Cisplatin‐based chemotherapy predisposes cancer patients to thromboembolic events.
Objectives: To investigate whether endothelial damage, via formation of procoagulant endothelial ...microparticles (EMPs), contributes to cisplatin‐related hypercoagulability.
Methods: Cell viability and caspase‐3/7 activities were assessed in two endothelial cell (EC) lines human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (HMVEC‐Ls) after exposure to cisplatin (1, 2.5, 5, 10 and 20 μm) for up to 120 h. Counts and procoagulant activity of EMPs were measured by flow cytometry and a thrombin generation assay, respectively. Tissue factor (TF) antigen and TF‐dependent procoagulant activity of EMP were determined by enzyme‐linked immunosorbent assay and a novel functional assay.
Results: By inducing apoptosis, cisplatin dose‐ and time‐dependently decreased the viability of confluent HUVECs and HMVEC‐Ls. Progression of EC death was accompanied by an increased release of EMPs (relative increase at 20 μm cisplatin for 48 h vs. control: HUVECs 6.5‐fold, P < 0.001; HMVEC‐Ls 18.4‐fold, P < 0.001). EMPs were highly procoagulant (relative increase at 20 μm cisplatin for 48 h vs. control: HUVECs 2.5‐fold, P < 0.001; HMVEC‐Ls 5.9‐fold, P < 0.001). EMP‐driven thrombin generation, however, was not dependent on TF: TF expression and TF procoagulant activity levels on microparticles were only marginal and EMP‐associated thrombin generation remained unchanged when the extrinsic pathway was blocked by omission of factor VIIa and/or incubation with an anti‐human TF antibody. In contrast, blocking of phospholipids by annexin V markedly diminished EMP‐associated procoagulant activity.
Conclusions: In vitro, cisplatin induced the release of EMPs that showed TF‐independent procoagulant activity.
Starch isolated from an under-utilized legume plant (pigeon pea) was carboxymethylated. Influences of reaction parameters were investigated on the degree of substitution (DS) and the reaction ...efficiency (RE). Studies showed that optimal DS of 1.12 could be reached at reaction efficiency of 80.6% in isopropanol–water reaction medium (40
°C, 3
h). Scanning electron microscopy showed that after carboxymethylation, the granular appearance of the native starch was distorted. Wide-angle X-ray diffractometry revealed that crystallinity was reduced significantly after carboxymethylation. The infrared spectra revealed new bands in the carboxymethyl starch at
ν
=
1600, 1426 and 1324
cm
−1 which were attributed to carbonyl functional groups vibration, –CH
2 scissoring and OH bending vibration, respectively. Broad-band
13C NMR of carboxymethyl starch showed an intense peak at
δ
=
180.3
ppm which was assigned to carbonyl carbon on the carboxymethyl substituent on the AGU (Anhydroglucose Unit). DEPT (Distortionless Enhancement by Polarization Transfer) 135 NMR showed negative signals which correspond to methylene carbons on the AGU. Differential Scanning Calorimetry (DSC) suggests loss of crystallinity after carboxymethylation. Thermogravimetry (TG), Derivative Thermogravimetry (DTG) and Differential Thermal Analysis (DTA) show that thermal stability improved after carboxymethylation. The study provides information on the preparation and characterization of a biomaterial from a new source which could be used alone or in the preparation of other functional polymers for diverse polymer applications.
Knowledge of vehicle dynamics data is important for vehicle control systems that aim to enhance vehicle handling and passenger safety. This study introduces observers that estimate lateral load ...transfer and wheel-ground contact normal forces, commonly known as vertical forces. The proposed method is based on the dynamic response of a vehicle instrumented with cheap and currently available standard sensors. The estimation process is separated into three blocks: the first block serves to identify the vehicle's mass, the second block contains a linear observer whose main role is to estimate the roll angle and the one-side lateral transfer load, while in the third block we compare linear and nonlinear models for the estimation of four wheel vertical forces. The different observers are based on a prediction/estimation filter. The performance of this concept is tested and compared with real experimental data acquired using the INRETS-MA (Institut National de Recherche sur les Transports et leur Sécurité - Département Mécanismes d'Accidents) Laboratory car. Experimental results demonstrate the ability of this approach to provide accurate estimation, thus showing its potential as a practical low-cost solution for calculating normal forces.
The motion of a vehicle is governed by the forces generated between the tyres and the road. Knowledge of these vehicle dynamic variables is important for vehicle control systems that aim to enhance ...vehicle stability and passenger safety. This study introduces a new estimation process for tyre/road forces. It presents many benefits over the existing state-of-art works, within the dynamic estimation framework. One of these major contributions consists of discussing in detail the vertical and lateral tyre forces at each tyre. The proposed method is based on the dynamic response of a vehicle instrumented with potentially integrated sensors. The estimation process is separated into two principal blocks. The role of the first block is to estimate vertical tyre forces, whereas in the second block two observers are proposed and compared for the estimation of lateral tyre/road forces. The different observers are based on a prediction/estimation Kalman filter. The performance of this concept is tested and compared with real experimental data using a laboratory car. Experimental results show that the proposed approach is a promising technique to provide accurate estimation. Thus, it can be considered as a practical low-cost solution for calculating vertical and lateral tyre/road forces.
This paper proposes a new estimation process to estimate tire-road forces, sideslip angle and wheel cornering stiffness. This method uses measurements from currently-available standard sensors. The ...estimation process is separated into two blocks: the first block contains an observer whose principal role is to calculate tire-road forces without a descriptive force model, while in the second block an observer estimates sideslip angle and cornering stiffness with an adaptive tire-force model. The different observers are based on an Extended Kalman Filter method. Concerning the vehicle model, for observability reasons, the rear longitudinal forces are neglected relative to the front longitudinal forces. The estimation process was applied and compared to real experimental data, notably wheel force measurements. Experimental results show the accuracy and potential of the estimation process, and a limitation in the estimation of the cornering stiffness.
Background: The pathogenesis and natural course of idiopathic upper extremity deep vein thrombosis (UEDVT) are unclear. Objective: To compare patients with UEDVT and with idiopathic lower extremity ...deep vein thrombosis (LEDVT) regarding risk factors and recurrence. Methods: We followed 50 patients with first idiopathic UEDVT and 841 patients with first idiopathic LEDVT for an average of 59 and 46 months, respectively. We excluded patients with natural inhibitor deficiency, lupus anticoagulant, cancer, pregnancy, isolated pulmonary embolism (PE), or long‐term antithrombotic treatment. The endpoint was recurrent venous thromboembolism (VTE). Results: In comparison to LEDVT patients, UEDVT patients were younger (38 ± 13 years vs. 49 ± 16 years, P < 0.001), slimmer (body mass index: 24 ± 4 vs. 27 ± 5, P < 0.001), less frequently had a family history of VTE (18% vs. 31%, P = 0.06) or concomitant PE (8% vs. 31%, P =0.001), were less frequently carriers of factor V Leiden (12% vs. 30%, P = 0.009), and had lower thrombin generation marker levels (D‐dimer, 283 ± 361 ng mL−1 vs. 456 ± 446 ng mL−1, P < 0.001; peak thrombin, 298 ± 101 nm vs. 363 ± 111 nm, P = 0.001). Recurrence occurred in two of 50 patients with UEDVT (4%) and in 129 of 841 patients with LEDVT (15%). After 5 years, the likelihood of recurrence was 2% 95% confidence interval (CI) 0–6 among UEDVT patients and 19% (95% CI 16–22; P = 0.02) among LEDVT patients. As compared to LEDVT patients, the adjusted risk of recurrence was 0.26 (95% CI 0.06–1.05; P = 0.059) in UEDVT patients. Conclusion: The pathogenesis and natural course of the disease differ between patients with idiopathic UEDVT and LEDVT.
Abnormalities in circadian rhythms play an important role in the pathogenesis of bipolar disorders (BD). Previous genetic studies have reported discrepant results regarding associations between ...circadian genes and susceptibility to BD. Furthermore, plausible behavioral consequences of at-risk variants remain unclear since there is a paucity of correlates with phenotypic biomarkers such as chronotypes. Here, we combined association studies with a genotype/phenotype correlation in order to determine which circadian genes variants may be associated with the circadian phenotypes observed in patients with BD. First, we compared the allele frequencies of 353 single nucleotide polymorphisms spanning 21 circadian genes in two independent samples of patients with BD and controls. The meta-analysis combining both samples showed a significant association between rs774045 in TIMELESS (OR = 1.49 95%CI1.18-1.88; p = 0.0008) and rs782931 in RORA (OR = 1.31 95%CI1.12-1.54; p = 0.0006) and BD. Then we used a "reverse phenotyping approach" to look for association between these two polymorphisms and circadian phenotypes in a subsample of patients and controls. We found that rs774045 was associated with eveningness (p = 0.04) and languid circadian type (p = 0.01), whereas rs782931 was associated with rigid circadian type (p = 0.01). Altogether, these findings suggest that these variants in the TIMELESS and RORA genes may confer susceptibility to BD and impact on circadian phenotypes in carriers who thus had lower ability to properly adapt to external cues.
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