To provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society. Methods: Seven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were "smell disorder," "olfactory dysfunction," "olfactory loss," "olfactory disturbance," "olfactory impairments," "olfaction disorder," "smell disorder," "anosmia," "cacosmia," and "dysosmia." Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A-strongly recommended to D-not recommended, were adopted for the management of olfactory dysfunction. Results: Both oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by $ This article is a secondary publication of the Guideline for the management of olfactory dysfunction published by the Japanese Rhinologic Society, which is
The high design luminosity of the SuperKEKB electron-positron collider is expected to result in challenging levels of beam-induced backgrounds in the interaction region. Properly simulating and mitigating these backgrounds is critical to the success of the Belle II experiment. We report on measurements performed with a suite of dedicated beam background detectors, collectively known as BEAST II, during the so-called Phase 1 commissioning run of SuperKEKB in 2016, which involved operation of both the high energy ring (HER) of 7 GeV electrons as well as the low energy ring (LER) of 4 GeV positrons. We describe the BEAST II detector systems, the simulation of beam backgrounds, and the measurements performed. The measurements include standard ones of dose rates versus accelerator conditions, and more novel investigations, such as bunch-by-bunch measurements of injection backgrounds and measurements sensitive to the energy spectrum and angular distribution of fast neutrons. We observe beam-gas, Touschek, beam-dust, and injection backgrounds. As there is no final focus of the beams in Phase 1, we do not observe significant synchrotron radiation, as expected. Measured LER beam-gas backgrounds and Touschek backgrounds in both rings are slightly elevated, on average three times larger than the levels predicted by simulation. HER beam-gas backgrounds are on on average two orders of magnitude larger than predicted. Systematic uncertainties and channel-to-channel variations are large, so that these excesses constitute only 1-2 sigma level effects. Neutron background rates are higher than predicted and should be studied further. We will measure the remaining beam background processes, due to colliding beams, in the imminent commissioning Phase 2. These backgrounds are expected to be the most critical for Belle II, to the point of necessitating replacement of detector components during the Phase 3 (full-luminosity) operation of SuperKEB.
β-Alanine is a precursor for coenzyme A (CoA) biosynthesis and is a substrate for the bacterial/eukaryotic pantothenate synthetase and archaeal phosphopantothenate synthetase. β-Alanine is synthesized through various enzymes/pathways in bacteria and eukaryotes, including the direct decarboxylation of Asp by aspartate 1-decarboxylase (ADC), the degradation of pyrimidine, or the oxidation of polyamines. However, in most archaea, homologs of these enzymes are not present; thus, the mechanisms of β-alanine biosynthesis remain unclear. Here, we performed a biochemical and genetic study on a glutamate decarboxylase (GAD) homolog encoded by TK1814 from the hyperthermophilic archaeon Thermococcus kodakarensis. GADs are distributed in all three domains of life, generally catalyzing the decarboxylation of Glu to γ-aminobutyrate (GABA). The recombinant TK1814 protein displayed not only GAD activity but also ADC activity using pyridoxal 5'-phosphate as a cofactor. Kinetic studies revealed that the TK1814 protein prefers Asp as its substrate rather than Glu, with nearly a 20-fold difference in catalytic efficiency. Gene disruption of TK1814 resulted in a strain that could not grow in standard medium. Addition of β-alanine, 4'-phosphopantothenate, or CoA complemented the growth defect, whereas GABA could not. Our results provide genetic evidence that TK1814 functions as an ADC in T. kodakarensis, providing the β-alanine necessary for CoA biosynthesis. The results also suggest that the GAD activity of TK1814 is not necessary for growth, at least under the conditions applied in this study. TK1814 homologs are distributed in a wide range of archaea and may be responsible for β-alanine biosynthesis in these organisms.
Immunohistochemical study revealed the presence of TRPV1, 2, 3, and 4 in the laryngeal epithelial cells. Chemoradiotherapy may reduce the expression of TRPV1, 2, 3, and 4, which might be a result of the mucositis and neuropathy in laryngeal epithelium.
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