Effects of cochlear implantation on binaural hearing in adults with unilateral hearing loss

A FDA clinical trial was carried out to evaluate the potential benefit of cochlear implant (CI) use for adults with unilateral moderate-to-profound sensorineural hearing loss. Subjects were 20 adults with moderate-to-profound unilateral sensorineural hearing loss and normal or near-normal hearing on the other side. A MED-EL standard electrode was implanted in the impaired ear. Outcome measures included: (a) sound localization on the horizontal plane (11 positions, −90° to 90°), (b) word recognition in quiet with the CI alone, and (c) masked sentence recognition with the target at 0° and the masker at −90°, 0°, or 90°. This battery was completed preoperatively and at 1, 3, 6, 9, and 12 months after CI activation. Normative data were also collected for 20 age-matched control subjects with normal or near-normal hearing bilaterally. The CI improved localization accuracy and reduced side bias. Word recognition with the CI alone was similar to performance of traditional CI recipients. The CI improved masked sentence recognition when the masker was presented from the front or from the side of normal or near-normal hearing. The binaural benefits observed with the CI increased between the 1- and 3-month intervals but appeared stable thereafter. In contrast to previous reports on localization and speech perception in patients with unilateral sensorineural hearing loss, CI benefits were consistently observed across individual subjects, and performance was at asymptote by the 3-month test interval. Cochlear implant settings, consistent CI use, and short duration of deafness could play a role in this result

Comparison of two cochlear implant coding strategies on speech perception

OBJECTIVE: Assess whether differences in speech perception are observed after exclusive listening experience with high-definition continuous interleaved sampling (HDCIS) versus fine structure processing (FSP) coding strategies. METHODS: Subjects were randomly assigned at initial activation of the external speech processor to receive the HDCIS or FSP coding strategy. Frequency filter assignments were consistent across subjects. The speech perception test battery included CNC words in quiet, HINT sentences in quiet and steady noise (+10 dB SNR), AzBio sentences in quiet and a 10-talker babble (+10 dB SNR), and BKB-SIN. Assessment intervals included 1, 3, and 6 months post-activation. RESULTS: Data from 22 subjects (11 with HDCIS and 11 with FSP) were assessed over time. Speech perception performance was not significantly different between groups. DISCUSSION: Speech perception performance was not significantly different after 6 months of listening experience with the HDCIS or FSP coding strategy

Popular and Populist Shakespearean Transcreations in Central and Eastern Europe

The article discusses the variety of ways in which the terms “popular” or “populist” could be associated with postwar Shakespearean transcreations in the Central and Eastern European region, pointing out how performers and adaptors challenged the canonical, highbrow status of Shakespeare and used his oeuvre as raw material in experimental forms and genres. Following a discussion on the variety of socio-historical contexts which inspired noteworthy popular and/or populist reworkings in several Central and Eastern European countries, the article takes a more in-depth look at a few specific comic genres, particularly the burlesque and the cabaret in a theoretical framework, and concludes by examining post-1989 experimental theatre practices

Attenuation of doxorubicin-induced cardiotoxicity by mdivi-1: a mitochondrial division/mitophagy inhibitor

Doxorubicin is one of the most effective anti-cancer agents. However, its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Given the multiple beneficial effects of the mitochondrial division inhibitor (mdivi-1) in a variety of pathological conditions including heart failure and ischaemia and reperfusion injury, we investigated the effects of mdivi-1 on doxorubicin-induced cardiac dysfunction in naïve and stressed conditions using Langendorff perfused heart models and a model of oxidative stress was used to assess the effects of drug treatments on the mitochondrial depolarisation and hypercontracture of cardiac myocytes. Western blot analysis was used to measure the levels of p-Akt and p-Erk 1/2 and flow cytometry analysis was used to measure the levels p-Drp1 and p-p53 upon drug treatment. The HL60 leukaemia cell line was used to evaluate the effects of pharmacological inhibition of mitochondrial division on the cytotoxicity of doxorubicin in a cancer cell line. Doxorubicin caused a significant impairment of cardiac function and increased the infarct size to risk ratio in both naïve conditions and during ischaemia/reperfusion injury. Interestingly, co-treatment of doxorubicin with mdivi-1 attenuated these detrimental effects of doxorubicin. Doxorubicin also caused a reduction in the time taken to depolarisation and hypercontracture of cardiac myocytes, which were reversed with mdivi-1. Finally, doxorubicin caused a significant elevation in the levels of signalling proteins p-Akt, p-Erk 1/2, p-Drp1 and p-p53. Co-incubation of mdivi-1 with doxorubicin did not reduce the cytotoxicity of doxorubicin against HL-60 cells. These data suggest that the inhibition of mitochondrial fission protects the heart against doxorubicin-induced cardiac injury and identify mitochondrial fission as a new therapeutic target in ameliorating doxorubicin-induced cardiotoxicity without affecting its anti-cancer properties

Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity

Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity

Self-assembly of bioactive peptides, peptide conjugates, and peptide-mimetic materials

Molecular self-assembly is a multi-disciplinary field of research, with potential chemical and biological applications. One of the main driving forces of self-assembly is molecular amphiphilicity, which can drive formation of complex and stable nanostructures. Self-assembling peptide and peptide conjugates have attracted great attention due to their biocompatibility, biodegradability and biofunctionality. Understanding assembly enables the better design of peptide amphiphiles which may form useful and functional nanostructures. This review covers self-assembly of amphiphilic peptides and peptide mimetic materials, as well as their potential applications

MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape

Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW bound HLA-B*57:01 canonically, adopting a dramatically different conformation than the TW10 peptide. This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. We further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by a 'molecular tension' between the adaptive and innate immune systems

Evolution of the properties of helium nanobubbles during in situ annealing probed by spectrum imaging in the transmission electron microscope

International audienceThe evolution of nanometric helium bubbles in silicon has been investigated using spatially resolved electron energy-loss spectroscopy during in situ annealing in the transmission electron microscope. This approach allows the simultaneous determination of both the morphology and the helium density in the bubbles at each step of the annealing. Structural modification and helium emission from bubbles of various diameters in the range 7.5 to 20 nm and various aspect ratios of 1.1 to 1.9 have been studied. We clearly show that helium emission takes place at temperatures where bubble migration had hardly started. At higher temperatures, the migration (and coalescence) of voids is clearly revealed. For helium density lower than 150 He nm −3 , the Cerofolini's model taking into account the thermodynamical properties of an ultradense fluid reproduces well the helium emission from the bubbles, leading to an activation energy of 1.8 eV. When bubbles exhibit a higher initial helium density, the Cerofolini's model fails to reproduce the helium emission kinetics. We ascribe this to the fact that helium may be in the solid phase and we propose a tentative model to take into account the properties of the solid