Cochlear Implantation of Bilaterally Deafened Patients with Tinnitus Induces Sustained Decrease of Tinnitus-Related Distress

Objective: Tinnitus is a common symptom of hearing impairment. Patients who are bilaterally hard of hearing are often affected by tinnitus. However, they cannot undergo any of the standard tinnitus therapies, since they rely on hearing. Cochlear implantation (CI) used to treat severe hearing disabilities, such as bilateral hearing loss, was also shown to reduce tinnitus. Our goal was to determine if CI induces sustained reduction of tinnitus. We performed prospective, longitudinal analyses of tinnitus-related distress in a uniform group of bilaterally deafened patients after CI. Patients and Methods: The homogenous sample consisted of 41 patients who met the inclusion criteria and were consecutively included in this study. The impact of unilateral CI on tinnitus-related distress, health-related quality of life (HRQoL), and hearing abilities was studied with validated instruments. The follow-up appointments were scheduled at 6, 12, and 24 months after CI surgery. During the appointments, hearing abilities were estimated with monosyllabic Freiburg test, whereas the tinnitus-related distress, the HRQoL, and the subjective hearing were measured with standard questionnaires [Tinnitus Questionnaire (TQ), Nijmegen Cochlear Implantation Questionnaire, and Oldenburg Inventory, respectively]. Results: Tinnitus-related distress decreased significantly from the mean TQ score of 35.0 (SD = 19.6) prior to surgery to the mean TQ = 27.54 (SD = 20.0) 6 months after surgery and remained sustained low until the end of follow-up period. In addition, CI significantly improved the hearing abilities and the HRQoL of all patients. Conclusion: The results from our prospective study suggest that in a homogenous sample of bilaterally deafened, implanted patients who report having tinnitus prior to surgery, CI alone not only improves the hearing abilities but also significantly reduces the tinnitus- related distress and improves the HRQoL in a sustained way

Percutaneous CT fluoroscopy-guided core biopsy of pancreatic lesions: technical and clinical outcome of 104 procedures during a 10-year period

Background: In unclear pancreatic lesions, a tissue sample can confirm or exclude the suspected diagnosis and help to provide an optimal treatment strategy to each patient. To date only one small study reported on the outcome of computed tomography (CT) fluoroscopy-guided biopsies of the pancreas. Purpose: To evaluate technical success and diagnostic rate of all CT fluoroscopy-guided core biopsies of the pancreas performed in a single university center during a 10-year period. Material and Methods: In this retrospective study we included all patients who underwent a CT fluoroscopy-guided biopsy of a pancreatic mass at our comprehensive cancer center between 2005 and 2014. All interventions were performed under local anesthesia on a 16-row or 128-row CT scanner. Technical success and diagnostic rates as well as complications and effective patient radiation dose were analyzed. Results: One hundred and one patients (54 women;mean age, 63.912.6 years) underwent a total of 104 CT fluoroscopy-guided biopsies of the pancreas. Ninety-eight of 104 interventions (94.2%) could be performed with technical success and at least one tissue sample could be obtained. In 88 of these 98 samples, a definitive pathological diagnosis, consistent with clinical success could be achieved (89.8%). Overall 19 minor and three major complications occurred during the intra- or 30-day post-interventional period and all other interventions could be performed without complications;there was no death attributable to the intervention. Conclusion: CT fluoroscopy-guided biopsy of pancreatic lesions is an effective procedure characterized by a low major complication and a high diagnostic rate

Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determine crystal structures of the complex and identify residues essential for the interaction. To corroborate the chaperone-like activity of PqsE, we design stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals

The evolution of early and late type galaxies in the COSMOS up to z~1.2

The Cosmic Evolution Survey (COSMOS) allows for the first time a highly significant census of environments and structures up to redshift one, as well as a full morphological description of the galaxy population. In this paper we present a study aimed to constrain the evolution, in the redshift range 0.2 < z < 1.2, of the mass content of different morphological types and its dependence on the environmental density. We use a deep multicolor catalog, covering an area of ~0.7 square degrees inside the COSMOS field, with accurate photometric redshifts (i < 26.5 and dz/(z+1) ~ 0.035). We estimate galaxy stellar masses by fitting the multi-color photometry to a grid of composite stellar population models. We quantitatively describe the galaxy morphology by fitting PSF convolved Sersic profiles to the galaxy surface brightness distributions down to F814 = 24 mag for a sample of 41300 objects. We confirm an evolution of the morphological mix with redshift: the higher the redshift the more disk-dominated galaxies become important. We find that the morphological mix is a function of the local comoving density: the morphology density relation extends up to the highest redshift explored. The stellar mass function of disk-dominated galaxies is consistent with being constant with redshift. Conversely, the stellar mass function of bulge-dominated systems shows a decline in normalization with redshift. Such different behaviors of late-types and early-types stellar mass functions naturally set the redshift evolution of the transition mass. ABRIDGEDComment: 19 pages, 17 figures. Accepted for publication in The Astrophysical Journa

The Pseudomonas aeruginosa Chemotaxis Methyltransferase CheR1 Impacts on Bacterial Surface Sampling

The characterization of factors contributing to the formation and development of surface-associated bacterial communities known as biofilms has become an area of intense interest since biofilms have a major impact on human health, the environment and industry. Various studies have demonstrated that motility, including swimming, swarming and twitching, seems to play an important role in the surface colonization and establishment of structured biofilms. Thereby, the impact of chemotaxis on biofilm formation has been less intensively studied. Pseudomonas aeruginosa has a very complex chemosensory system with two Che systems implicated in flagella-mediated motility. In this study, we demonstrate that the chemotaxis protein CheR1 is a methyltransferase that binds S-adenosylmethionine and transfers a methyl group from this methyl donor to the chemoreceptor PctA, an activity which can be stimulated by the attractant serine but not by glutamine. We furthermore demonstrate that CheR1 does not only play a role in flagella-mediated chemotaxis but that its activity is essential for the formation and maintenance of bacterial biofilm structures. We propose a model in which motility and chemotaxis impact on initial attachment processes, dispersion and reattachment and increase the efficiency and frequency of surface sampling in P. aeruginosa

Single-centre experience and practical considerations of the benefit of a second cochlear implant in bilaterally deaf adults

Purpose: Bilateral cochlear implant (CI) implantation is increasingly used in the auditory rehabilitation of bilaterally deafened adults. However, after successful unilateral implantation, objective patient counselling is essential. Methods: We investigated the extra benefit of a second CI in adults in terms of health-related quality of life, tinnitus, stress, anxiety, depression, quality of hearing, and speech recognition. Hearing ability was assessed by using the Freiburg monosyllable speech discrimination test (FB MS) and the Oldenburg sentence test with azimuth variations. In a prospective patient cohort, we administered validated questionnaires before a CI, after a first CI and after a second CI implantation. Results: The study included 29 patients, made up of nine women and 20 men. The median time between the first and the second implantation was 23 months. The mean total NCIQ score and TQ before a CI improved significantly after both implantations. Stress, anxiety, and depression were stable over time and were not significantly affected by CI implantations. Speech recognition with noise significantly improved after the first and again after the second CI. Correlation analysis showed a strong connection between auditory performance and HRQoL. Conclusion: We demonstrated that a unilateral CI benefitted many fields and that the second sequential CI leads again to additional improvement. Bilateral CI implantation should, therefore, be the standard form of auditory rehabilitation in deafened adults

Redox-guided axonal regrowth requires cyclic GMP dependent protein kinase 1 : implication for neuropathic pain

Cyclic GMP-dependent protein kinase 1 (PKG1) mediates presynaptic nociceptive long-term potentiation (LTP) in the spinal cord and contributes to inflammatory pain in rodents but the present study revealed opposite effects in the context of neuropathic pain. We used a set of loss-of-function models for in vivo and in vitro studies to address this controversy: peripheral neuron specific deletion (SNS-PKG1-/-), inducible deletion in subsets of neurons (SLICK-PKG1-/-) and redox-dead PKG1 mutants. In contrast to inflammatory pain, SNS-PKG1-/- mice developed stronger neuropathic hyperalgesia associated with an impairment of nerve regeneration, suggesting specific repair functions of PKG1. Although PKG1 accumulated at the site of injury, its activity was lost in the proximal nerve due to a reduction of oxidation-dependent dimerization, which was a consequence of mitochondrial damage in injured axons. In vitro, PKG1 deficiency or its redox-insensitivity resulted in enhanced outgrowth and reduction of growth cone collapse in response to redox signals, which presented as oxidative hotspots in growing cones. At the molecular level, PKG1 deficiency caused a depletion of phosphorylated cofilin, which is essential for growth cone collapse and guidance. Hence, redox-mediated guidance required PKG1 and consequently, its deficiency in vivo resulted in defective repair and enhanced neuropathic pain after nerve injury. PKG1-dependent repair functions will outweigh its signaling functions in spinal nociceptive LTP, so that inhibition of PKG1 is no option for neuropathic pain

Redox-guided axonal regrowth requires cyclic GMP dependent protein kinase 1: Implication for neuropathic pain

Cyclic GMP-dependent protein kinase 1 (PKG1) mediates presynaptic nociceptive long-term potentiation (LTP) in the spinal cord and contributes to inflammatory pain in rodents but the present study revealed opposite effects in the context of neuropathic pain. We used a set of loss-of-function models for in vivo and in vitro studies to address this controversy: peripheral neuron specific deletion (SNS-PKG1-/-), inducible deletion in subsets of neurons (SLICK-PKG1-/-) and redox-dead PKG1 mutants. In contrast to inflammatory pain, SNS-PKG1-/- mice developed stronger neuropathic hyperalgesia associated with an impairment of nerve regeneration, suggesting specific repair functions of PKG1. Although PKG1 accumulated at the site of injury, its activity was lost in the proximal nerve due to a reduction of oxidation-dependent dimerization, which was a consequence of mitochondrial damage in injured axons. In vitro, PKG1 deficiency or its redox-insensitivity resulted in enhanced outgrowth and reduction of growth cone collapse in response to redox signals, which presented as oxidative hotspots in growing cones. At the molecular level, PKG1 deficiency caused a depletion of phosphorylated cofilin, which is essential for growth cone collapse and guidance. Hence, redox-mediated guidance required PKG1 and consequently, its deficiency in vivo resulted in defective repair and enhanced neuropathic pain after nerve injury. PKG1-dependent repair functions will outweigh its signaling functions in spinal nociceptive LTP, so that inhibition of PKG1 is no option for neuropathic pain. Keywords: Sensory neuron, Nerve regeneration, Pain, Growth cone, Signaling ROS, Cofilin, Redo

Preparing single SiV − center in nanodiamonds for external, optical coupling with access to all degrees of freedom

International audienc

A chemical proteomics approach to identify c-di-GMP binding proteins in Pseudomonas aeruginosa.

In many bacteria, high levels of the ubiquitous second messenger c-di-GMP have been demonstrated to suppress motility and to promote the establishment of surface-adherent biofilm communities. While molecular mechanisms underlying the synthesis and degradation of c-di-GMP have been comprehensively characterized, little is known about how c-di-GMP mediates its regulatory effects. In this study, we have established a chemical proteomics approach to identify c-di-GMP interacting proteins in the opportunistic pathogen Pseudomonas aeruginosa. A functionalized c-di-GMP analog, 2'-aminohexylcarbamoyl-c-di-GMP (2'-AHC-c-di-GMP), was chemically synthesized and following its immobilization used to perform affinity pull down experiments. Enriched proteins were subsequently identified by high-resolution mass spectrometry. 2'-AHC-c-di-GMP was also employed in surface plasmon resonance studies to evaluate and quantify the interaction of c-di-GMP with its potential target molecules in vitro. The biochemical tools presented here may serve the identification of novel classes of c-di-GMP effectors and thus contribute to a better characterization and understanding of the complex c-di-GMP signaling network