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Obesity and associated metabolic disorders have become highly prevalent diseases worldwide, and the human gut microbiota, due to its influence on host energy metabolism, has been attributed an important role therein. This pilot study explores host-microbiota relationships in men and women affected by various types of glucose metabolism disorder. Among 20 individuals aged 58 to 71 years with either normal glucose tolerance, prediabetes, or type 2 diabetes mellitus the gut bacterial communities were compared based on barcoded 454 sequencing of 16S rRNA genes amplified from stool samples. We found that specific microbiota groups were relatively enriched or reduced in different metabolic states. Further, positive or negative associations with clinical manifestations of metabolic disease suggest that these organisms indicate and possibly contribute to metabolic impairment or health. For instance, a higher prevalence of Erysipelotrichaceae and Lachnospiraceae was found associated with metabolic disorders, and the Holdemania and Blautia genera correlated with clinical indicators of an impaired lipid and glucose metabolism. The Bacteroidetes and groups therein, by contrast, displayed inverse relationships with metabolic disease parameters and were found relatively enriched in participants not diagnosed with metabolic syndrome or obesity. Further, the prevalence of specific Clostridia and Rikenellaceae members also pointed towards a healthier metabolic state. Links with diet as an intermediate factor included positive and negative associations of Lachnospiraceae with relative consumption rates of fat and carbohydrates, respectively, and positive associations of Turicibacteraceae with the consumption of protein. Identifying critical roles of major gut microbiota components in metabolic disorders has important translational implications regarding the prevention and treatment of metabolic diseases by means of preventing or reversing dysbiosis and by controlling exacerbating diet and life style factors particularly in sensitive population groups.

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BACKGROUND: Due to the increased frequency of screening tests in new-born infants, the number of subsequent examinations of very young children has increased in the Departments of Phoniatrics and Pediatric Audiology. To exclude hearing loss in young children, click stimulated brainstem evoked response audiometry (BERA) and otoacoustic emission tests are, in general, considered to be reliable methods. However, pathologic BERA thresholds and pathologic hearing reactions have been observed occasionally in young infants who show improved and even normal hearing reactions in subjective and objective hearing tests after some months. PATIENTS AND RESULTS: Our group of 14 children (ten female, four male) was initially examined by BERA at the ages of 1-7 months. Twelve children had an elevated risk of hearing loss due to complications in the pre-, peri- and postnatal period. In the BERA, no deafness was diagnosed, but in all children at least monaural pathologic BERA thresholds were observed. Subjective hearing tests confirmed hearing loss. Objective and even subjective hearing reactions improved and normalised within a few months at least monaurally. CONCLUSION: In very young infants, the possibility of a delayed maturation of the auditory pathways must be considered when a hearing loss is diagnosed. Our examples prove that young children with sensorineural hearing loss need more than one objective hearing examination during the first year of life.

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The present multicentric clinical study involves 19 centres, 16 of them in German-speaking countries, 1 British, 1 Polish and 1 Hungarian. 60 postlingually deafened adults with a mean age of 47.5 years (20-70) and mean duration of deafness of 5.3 years (0.5-20) have been evaluated with the MED-EL COMBI 40 cochlear implant which implements a high-rate continuous-interleaved-sampling strategy with 8 channels. Safety and effectiveness data have been collected. Speech perception tests include a 16-consonant, an 8-vowel, a sentence and a monosyllabic-word test in all languages and a 2-digit figure test in all languages but English. Test intervals are 1, 3, 6 months and 1 year after first fitting. 41 of the 60 postlingually deafened adult study patients have completed their 6-month evaluation. While their pre-operative monosyllabic-word score was 0%, their mean monosyllabic-word score 6 months after first fitting was 48% (8-90) with a median of 50%. The mean sentence understanding was 84% (24-100) with a median of 90%. The respective values for the 1-year evaluations with 25 patients are a mean of 50% (5-85), with a median of 60% for the monosyllables and a mean of 89% (30-100), with a median of 97%, for the sentences.

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A disturbed cellular calcium homeostasis is suggested to play a pivotal role in neuronal damage. Energy deficiency causes depolarization of the neuronal membrane and Ca2+ enters the cells through different ion channels, the voltage-sensitive L-type Ca2+ channels and the NMDA-operated channels being the main gates. In the present study we used primary cultures of rat hippocampal neurons to demonstrate that the dihydropyridine calcium antagonist nimodipine, the non-competitive NMDA antagonists dizocilpine and memantine, as well as the AMPA antagonist NBQX (2,3-dihydroxy-6-nitro -7-sulfamoyl-benzo(F)quinoxaline), attenuate the glutamate-induced neuronal damage dose-dependently. Nimodipine applied simultaneously with NMDA-antagonists and NBQX, respectively, resulted in somewhat greater neuroprotection of glutamate-treated neurons compared with the effects of these agents applied singly. The type of interaction is best described by an independent action in combination, which means that the relative effects of nimodipine were not enhanced. Therefore, it can be considered as a lack of potentiation.

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The introduction of digital technology for programming and new signal processing in modern hearing aid systems has led to considerable progress in rehabilitation of hearing impairments. In this report, our experience with the clinical use of one-band and multiband digitally programmable hearing aids for children with sensorineural hearing impairment is described. In 65 children with various threshold configurations and degrees of hearing impairment, different programmable digital hearing aids were fitted. Various audiometric tests, fitting methods, and subjective patient responses were used in order to examine the possibilities and limits of hearing aid use. Multiband hearing devices gave the best results in clinical tests as well as with regard to subjective patient responses. This study shows the potential of this new hearing aid technology as an alternative for a variety of pediatric hearing impairments.

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At which time-point and to what extent do N-methyl-D-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors and L-type voltage-sensitive Ca2+ channels (VSCC) contribute to glutamate-induced neuronal injury? To address this question, we induced glutamate neurotoxicity in two neuronal culture systems, chick telencephalic neurons and rat hippocampal neurons, and tested selective antagonists for their neuroprotective activity when administered either during the excitotoxic insult (acute treatment) or during the recovery period (posttreatment). In cultured chick telencephalic neurons exposed to 1 mM L-glutamate for 60 min, both the NMDA receptor antagonist dizocilpine (MK-801; 0.1 microM) and the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1 microM) completely blocked glutamate-induced neuronal injury when applied concomitantly with glutamate. If the antagonists were applied during the recovery period, dizocilpine at concentrations up to 10 microM only moderately increased cell viability, whereas CNQX showed a neuroprotective activity comparable to that observed in the case of the acute treatment. In cultured rat hippocampal neurons, excitotoxic injury was induced by a 30-min exposure to 1 microM glutamate. Treatment with dizocilpine during the glutamate exposure could rescue the hippocampal neurons from the excitotoxic insult, whereas acute treatment with the AMPA/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX) or the L-type VSCC blocker nimodipine showed no protection. In contrast, all three drugs showed neuroprotective activity when applied 30, 60 or 120 min after the glutamate exposure. Surprisingly, when the onset of the treatment was delayed for even 240 min, only NBQX and nimodipine led to a reduction in excitotoxic neuronal injury. We conclude that activation of AMPA/kainate receptors and L-type VSCC is critically involved in a late stage of glutamate neurotoxicity, thereby allowing pharmacological intervention at a time when blockade of NMDA receptors becomes less efficacious.

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Several reports have indicated that the two glutamate receptor antagonists, dizocilpine (that binds to the phencyclidine recognition site of the NMDA (N-methyl-D-aspartate) receptor) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline, that binds to the AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole) receptor), protect neurons against damage caused by hypoxia, ischemia or excitotoxicity. We, therefore, used a combination of these drugs to achieve enhanced neuroprotection. Primary cultures of rat hippocampal neurons were challenged by glutamate intoxication. Both dizocilpine and NBQX produced dose-dependent increases in the percentage of viable neurons. Combined treatment with both glutamate receptor antagonists had an over-additive neuroprotective effect. Simultaneous administration of dizocilpine and NBQX also had a pronounced neuroprotective effect in vivo in mice subjected to focal cerebral ischemia and rats with global forebrain ischemia. This suggest that such a combination may have therapeutic relevance.

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Detection of hearing impairment in early childhood is difficult. We serially recorded transient evoked otoacoustic emissions (TEOAEs) to search for signs of ototoxicity in term, healthy newborns and compared the results to a second group of term babies treated for perinatally acquired bacterial infection with ampicillin plus either cefotaxime or plus aminoglycoside. At initial evaluation, in the group of 45 healthy children born at term, well reproducible emissions were observed in all but two children. In each of these two, initially well reproducible TEOAEs were detected in one ear only. At the time of the second recording (mean at day 8.5) excellent emissions were seen in all ears of all children. Similarly, in the second group receiving ampicillin plus either cefotaxime or plus aminoglycoside, the height of emissions as well as TEOAE-reproducibility was equal or even increased at the time of the second evaluation in all 17 patients. In the following group of 59 patients, all receiving ampicillin plus aminoglycoside, again TEOAEs were equal or improved at the time of follow-up examinations. In all patients, a reduced general condition tended to be associated with less reproducible TEOAEs. We conclude that at conventional doses in low-risk infants, aminoglycosides are unlikely to cause ototoxicity and that in early childhood serial TEOAE-recording may be useful for evaluation of inner ear function.

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Trehalose 6-phosphate synthase, catalyzing the reaction between UDP-glucose and glucose 6-phosphate and forming trehalose 6-phosphate, was isolated and partially purified (30-fold) from the phototrophic, halo-alkaliphilic bacterium Ectothiorhodospira halochloris. The activity is stabilized by 20 mM MgCl2, 50 mM NaCe and 2M glycine betaine. The molecular weight was 63000. The enriched enzyme had a MgCl2 optimum at 3-6mM, a pH optimum at 7.5 (in Tris-HCl buffer) and a temperature optimum at 50 degrees C. The Km-values were 1.5 x 10(-3) M for UDP-glucose and 2 x 10(-3) M for glucose 6-phosphate. The enzyme showed a salinity dependence with optimal concentrations between 100 and 300mM salt. Higher concentrations of salt resulted in a decrease in activity. In the presence of inhibitory salt concentrations the compatible solute glycine betaine had a protective effect with a maximum between 0.5 and 2.0M.

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