Auf Tribenzotriquinacen und Fulleren basierende supramolekulare Aggregate: Baukastenprinzip funktioneller Nano-Module

Im Rahmen der vorliegenden Arbeit wurden zwei neuartige Rezeptoren synthetisiert, die eine optimierte Passform für C60 besitzen. Die anschließenden spektroskopischen Untersuchungen mit C60 haben Aufschluss über die Zusammensetzung und die jeweilige Stärke der Wirt-Gast-Komplexe in Lösung gegeben. Diese grundlegende Selbstorganisations-Strategie aufgreifend, konnte der variable Einsatz von Rezeptor-Bausteinen und funktionalisierten Fullerenen, ebenfalls mittels Komplexierungsstudien, gezeigt werden. Diese Ergebnisse geben das positive Signal, dass weitere Untersuchungen zu molekularen Ratschen und Motoren auf dieser Basis möglich und sinnvoll sind. Um elementare Erkenntnisse zur Fixierung von Tribenzotriquinacenen auf Oberflächen realisieren zu können, wurde abschließend ein am "Rückgrat" funktionalisiertes Tribenzotriquinacen synthetisiert. Dieses konnte in einer gemischten Monolage zusammen mit Hexan- bzw. Decanthiol auf Gold-(111) immobilisiert und mit einem Rastertunnelmikroskop detektiert und untersucht werden.In the present doctoral thesis two novel receptors have been synthesized that provide a structurally optimized fit for fullerene C60. The subsequent spectroscopic studies with C60 gave information about the composition and the respective strengths of the host-guest complexes in solution. By picking up this basic self-organization strategy, the variable use of receptorblock and functionalized fullerenes was demonstrated by using spectroscopic studies as well, whereby the possible feasibility of molecular ratchets and motors was confirmed. Finally, a backbone-functionalized tribenzotriquinacene was synthesized, immobilized as a mixed monolayer with hexane- or decanethiol on gold-(111) and detected and investigated with a scanning tunneling microscope to carry out basic studies on surfaces

The Effectiveness of Bilateral Cochlear Implants for Severe-to-Profound Deafness in Adults:A Systematic Review

<p>Objective: Assessment of the clinical effectiveness of bilateral cochlear implantation compared with unilateral cochlear implantation or bimodal stimulation, in adults with severe-to-profound hearing loss. In 2007, the National Institute for Health and Clinical Excellence (NICE) in the U. K. conducted a systematic review on cochlear implantation. This study forms an update of the adult part of the NICE review.</p><p>Data Sources: The electronic databases MEDLINE and Embase were searched for English language studies published between October 2006 and March 2011.</p><p>Study Selection: Studies were included that compared bilateral cochlear implantation with unilateral cochlear implantation and/or with bimodal stimulation, in adults with severe-to-profound sensorineural hearing loss. Speech perception in quiet and in noise, sound localization and lateralization, speech production, health-related quality of life, and functional outcomes were analyzed.</p><p>Data Extraction: Data extraction forms were used to describe study characteristics and the level of evidence.</p><p>Data Synthesis: The effect size was calculated to compare different outcome measures.</p><p>Conclusion: Pooling of data was not possible because of the heterogeneity of the studies. As in the NICE review, the level of evidence of the included studies was low, although some of the additional studies showed less risk of bias. All studies showed a significant bilateral benefit in localization over unilateral cochlear implantation. Bilateral cochlear implants were beneficial for speech perception in noise under certain conditions and several self-reported measures. Most speech perception in quiet outcomes did not show a bilateral benefit. The current review provides additional evidence in favor of bilateral cochlear implantation, even in complex listening situations.</p>

Characteristics of hearing loss in HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome

Haploinsufficiency of the zinc finger transcription factor GATA3 causes the triad of hypoparathyroidism, deafness and renal dysplasia, known by its acronym HDR syndrome. The purpose of the current study was to describe in detail the auditory phenotype in human HDR patients and compare these to audiometrical and histological data previously described in a mouse model of this disease. Pure tone audiometry, speech audiometry, speech in noise, auditory brainstem responses and transiently evoked otoacoustic emissions were measured in 2 patients affected by HDR syndrome. Both patients were affected by a moderate-to-severe sensorineural hearing loss. Speech reception thresholds were shifted and speech recognition in noise was disturbed. No otoacoustic emissions could be generated in either patient. Auditory brainstem response interpeak intervals were normal. The human and murine audiological phenotypes seem to correspond well. Hearing loss in HDR syndrome is moderate to severe, seems to be slightly worse at the higher end of the frequency spectrum and may be progressive with age. The absence of otoacoustic emissions and the loss of frequency selectivity suggest an important role for outer hair cells in causing the hearing los

Is hearing loss a feature of Joubert syndrome, a ciliopathy?

Objective To assess if hearing loss is a feature of Joubert syndrome (JBS). one of the ciliopathies and therefore possibly associated with hearing loss Design: Retrospective case series. Setting University Children's Hospital Patients Dutch patients with JBS. Main outcome measures Audiological data. Results: Data from 22 Dutch Joubert syndrome (JBS) cases (17 males, 5 females) aged 3-40 years were available. Audiological tests were successfully performed in 14 cases Three cases (aged 17-26 years) showed very mild sensorineural hearing loss (SNHL) at different frequencies. Conductive hearing loss due to middle ear infections occurred frequently in young JBS children (6 out of 22 cases) In three cases (aged 3-13 years) the parents reported the child was hypersensitive to sound. Conclusion We found no evidence for significant hearing loss in Joubert syndrome patients. However, given the compromised speech development in JBS, conductive hearing loss due to middle ear infections should be treated vigorously SNHL at a later age cannot be excluded on the basis of our data, given the sample size Three of the older cases showed discretely Increased hearing thresholds Analogous to the ciliopathy Bardet-Biedl syndrome, where hearing thresholds were reported to be subclinically increased in a group of adolescents patients, we recommend follow-up of JBS patients in view of the possibility of progressive, late-onset SNHL. (C) 2010 Elsevier Ireland Ltd. All rights reserve

Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection

OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood. METHODS: Infants <32 weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months' corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life

Pharmacokinetics and safety of tobramycin nebulization with the I-neb and PARI-LC Plus in children with cystic fibrosis : A randomized, crossover study

AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I-neb device to the standard PARI-LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open-label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I-neb (75 mg) and PARI-LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM-1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. RESULTS: Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS-induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I-neb. CONCLUSIONS: Nebulization of 75 mg TIS with the I-neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI-LC Plus and was well tolerated and preferred over the PARI-LC Plus. Long-term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury

Effect of unilateral and simultaneous bilateral cochlear implantation on tinnitus: A Prospective Study

Objectives/HypothesisTo determine the effect of cochlear implantation on tinnitus perception in patients with severe bilateral postlingual sensorineural hearing loss and to demonstrate possible differences between unilateral and bilateral cochlear implantation. Study DesignProspective study. MethodsThirty-eight adult patients were included in this prospective study, as part of a multicenter randomized controlled trial investigating the benefits of bilateral cochlear implantation versus unilateral cochlear implantation. Pre- and postoperative tinnitus perception scores were evaluated, before and 1 year after implantation on three tinnitus questionnaires; the Tinnitus Handicap Inventory (THI), the Tinnitus Questionnaire (TQ), and a visual analogue scale for tinnitus burden. ResultsBefore implantation, the tinnitus prevalence was 42.1% (16 of 38) in the whole study group. One year after implantation, the tinnitus questionnaire scores had decreased in 71.4% according to the TQ and 80.0% according to the THI. Tinnitus was induced after cochlear implantation in six patients, five in the bilateral and one in the unilateral group. ConclusionsOur study shows that cochlear implantation is effective in the reduction of tinnitus in patients with bilateral sensorineural hearing loss who suffered from preoperative tinnitus. Conversely, tinnitus may also increase or even be induced by the cochlear implantation itself. Cochlear implant candidates should be well informed about these possible consequences before undergoing surgery. Level of Evidence2b Laryngoscope, 126:956-961, 201