Adv Exp Med Biol
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Cochlear implant (CI) users can derive a musical pitch from the temporal pattern of pulses delivered to one electrode. However, pitch perception deteriorates with increasing pulse rate, and most listeners cannot detect increases in pulse rate beyond about 300 pps. In addition, previous studies using irregular pulse trains suggest that pitch can be substantially influenced by neural refractory effects. ⋯ Behavioural results replicated the deterioration in rate discrimination at rates above 200-300 pps and the finding that pulse trains whose inter-pulse intervals (IPIs) alternate between a shorter and a longer value (e.g. 4 and 6 ms) have a pitch lower than that corresponding to the mean IPI. To link ECAP modulation to pitch, we physically modulated a 200-pps pulse train by attenuating every other pulse and measured both ECAPs and pitch as a function of modulation depth. Our results show that important aspects of temporal pitch perception cannot be explained in terms of the AN response, at least as measured by ECAPs, and suggest that pitch is influenced by refractory effects occurring central to the AN.
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Sarcoidosis is a granulomatous multiorgan diseases with an unknown etiology, with the predominant lung involvement. Immunosuppressive agents such as corticosteroids, methotrexate, azathioprinum, ciclosporinum A, chlorambucil, cyclophosphamide, hydroxychlorochinum, indomethacin, pentoxyfillinum, thalidomide, leflunomidum, and adalimumab, or infliximab have been used in its treatment. It should be emphasized that the Summary of Products Characteristics (SPC) of these drugs does not specifically recommend their use in the therapy for sarcoidosis. ⋯ The doctrine of law assumes that the off-label use constitutes a medical experiment. Therefore, the commencement of therapy with such drugs requires patients' informed consent, which must be kept along with other medical records. Insufficient knowledge of the legal regulations may result in civil and professional liability of a physician supervising the therapy of a sarcoidosis patient, especially in case of adverse effects.
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Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the translation and stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is initiated through specific base-pairing interactions between the 5' end ("seed" region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR lead to more effective mRNA destabilization. ⋯ To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers.
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Pulmonary tuberculosis (TB) remains a global health concern with an astounding 9 million new cases and 2 million deaths per year. This leading infectious cause of death remains highly prevalent with one third of the world's population latently infected with Mycobacterium tuberculosis (M.tb) despite routine vaccination against TB in endemic areas. The only approved TB vaccine is the Bacille Calmette-Guerin (BCG), which provides protection against childhood miliary tuberculosis and has been administered intradermally in humans for almost a century. ⋯ Growing evidence supports that the route of immunization dictates the geographical location of TB-reactive T cells, and it is this distribution which predicts the protective outcome of such vaccine-elicited immunity. Such vaccines that are able to localize TB-reactive T cells to the lung and airway mucosa are thought to fill the "immunological gap" in the lung that is required for enhanced protection against M.tb infection. This chapter focuses on the critical importance of T cell geography when designing new immunization strategies against pulmonary TB.
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Randomized Controlled Trial
Indacaterol add-on therapy improves lung function, exercise capacity and life quality of COPD patients.
Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory condition, involving airways and lung parenchyma. The disease leads to airflow limitation, and pulmonary hyperinflation, resulting in dyspnea, decreased exercise tolerance, and impaired quality of life. COPD pharmacotherapy guidelines are based on a combination of long-acting beta2-agonists (LABA), long-acting antimuscarinic agents (LAMA) and methyloxantins. ⋯ We also found that the degree of desaturation before and after 6MWD, and fatigue levels significantly improved in the indacaterol group. The patients' quality of life also changed favorably in the indacaterol treatment arm. We conclude that the add-on therapy with indacaterol exerts positive effects in COPD patients.