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Objective: To determine the frequency‐specific benefits of ossicular chain preservation compared to performing disarticulations and reconstructions in transmastoid facial nerve decompression surgery in patients with an intact ossicular chain. Methods: A retrospective chart review (January 2007 and June 2018) of patients undergoing transmastoid facial nerve decompression on the intact middle ear for severe facial palsy at a tertiary referral center. Surgery was performed with ossicular chain disarticulation on an as‐needed basis using either ossicular chain preservation (without ossicular disarticulation), incudostapedial separation, or incus disarticulation technique. Hearing outcomes were assessed. Results: The 108 patients were included in this study. Among these, 89 patients underwent ossicular chain preservation, 5 underwent incudostapedial separation and 14 underwent incus repositioning. The proportion of patients with a change in the 4‐frequency air conduction pure‐tone average of less than 10 dB was 91%, 60%, and 50%, respectively, for the three surgical techniques; these were significantly different (Fisher's exact test, p <.001). Frequency‐specific analysis showed that air conduction was significantly better following the ossicular chain preservation technique compared with the incus repositioning technique at stimulation frequencies lower than 250 Hz and higher than 2000 Hz, and compared with the incudostapedial separation technique at 4000 Hz. Analysis of biometric measures determined on CT images suggested that the feasibility of the ossicular chain preservation technique correlates with incus body thickness on coronal CT images. Conclusions: Ossicular chain preservation is an effective approach for hearing preservation in transmastoid facial nerve decompression or similar surgical procedures. To determine the frequency‐specific benefits of ossicular chain preservation compared to performing disarticulations and reconstructions in transmastoid facial nerve decompression surgery in patients with intact ossicular chain. Frequency‐specific analysis showed that air conduction was significantly better following the ossicular chain preservation technique compared with the incus repositioning technique at stimulation frequencies lower than 250 Hz and higher than 2000 Hz, and compared with the incudostapedial separation technique at 4000 Hz. Ossicular chain preservation is an effective approach for hearing preservation in transmastoid facial nerve decompression or similar surgical procedures. [ABSTRACT FROM AUTHOR]

The hypothalamus receives ingested nutrient information via ascending gut-related projections and plays a significant role in the regulation of food intake. Human neuroimaging studies have observed changes in the activity or connectivity of the hypothalamus in response to nutrient ingestion. However, previous neuroimaging studies have not yet assessed differences in temporal changes of hypothalamic responses to various nutrients in humans. Thus a repeated measures functional magnetic resonance imaging (fMRI) study using 30-min scans was designed to examine differences in hypothalamic responses to various nutrients. In this study, 18 healthy adults (mean age, 22.4 years; standard deviation, 4.8; age range, 19–39 years; 11 males and seven females) underwent fMRI sessions. On the day of each session, one of the four solutions (200 ml of monosodium glutamate, glucose, safflower oil emulsion, or saline) was administered to participants while fMRI scanning. Infused amino acid and glucose, but not lipid emulsion, increased lateral hypothalamic responses as compared to a saline infusion ([x, y, z] = [4, −4, −10], z = 2.96). In addition, only hypothalamic responses to saline, but not those to the infusion of other nutrients, elicited a subjective sensation of hunger. These findings suggest that lateral hypothalamic responses to ingested nutrients may mediate homeostatic sensations in humans. [ABSTRACT FROM AUTHOR]

Several studies have reported sudden sensorineural hearing loss (SHL) as an initial symptom of acoustic neuromas (ANs). We aimed to retrospectively evaluate the incidence of SHL and the associated rates of post-treatment improvement in patients diagnosed with ANs. We analysed the clinical data of 686 patients with ANs and examined tumour size, correlation with hearing loss, number of episodes of SHL, extent of auditory recovery, and associated audiogram patterns. Among 686 enrolled patients with ANs, 232 (86 with intracanalicular and 146 with extrameatal tumours) experienced SHL at some point in their clinical history. The incidence of SHL was not significantly associated with tumour size. Of the 172 patients analysed, 119, 44, and 9 patients experienced one, two, or three or more episodes of SHL, respectively. Confirmed auditory recovery occurred in 61%, 45.3%, and 33.3% of the patients after the first, second, or third or later episodes of SHL, respectively. The audiograms of 78/172 (45.3%) patients showed a typical trough-shaped pattern of hearing loss at medium-level frequencies. Among patients with ANs, 7.7% experienced two or more episodes of SHL. The recovery rate of SHL decreased with each successive occurrence. [ABSTRACT FROM AUTHOR]

This study aimed to develop and validate a Japanese version of the Tinnitus Acceptance Questionnaire (TAQ), an instrument that measures the process of intentional acceptance of adverse experiences associated with tinnitus. A total of 125 patients with chronic tinnitus from multiple institutions participated in this study. Participants completed the Japanese versions of the TAQ, Tinnitus Handicap Inventory, Valuing Questionnaire, Acceptance and Action Questionnaire-II, and Hospital Anxiety and Depression Scale. A second TAQ was administered 1–2 weeks later. Because the model fitted poorly in confirmatory factor analysis, exploratory factor analysis was conducted, which yielded a two-factor structure that was divided into forward and reversed item groups. Hypotheses regarding criterion and construct validity were clearly supported. A high Cronbach's α coefficient value was obtained for the TAQ total score (0.88). The interclass correlation coefficient for test–retest reliability was within the acceptable range (0.95). The results of the exploratory factor analysis were considered to be due to artifacts caused by the characteristics of the Japanese language. The present study confirmed the validity and reliability of the Japanese version of the TAQ in measuring tinnitus-specific receptivity. [ABSTRACT FROM AUTHOR]

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors for a wide range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed "DrugMap," an atlas of cysteine ligandability compiled across 416 cancer cell lines. We unexpectedly find that cysteine ligandability varies across cancer cell lines, and we attribute this to differences in cellular redox states, protein conformational changes, and genetic mutations. Leveraging these findings, we identify actionable cysteines in NF-κB1 and SOX10 and develop corresponding covalent ligands that block the activity of these transcription factors. We demonstrate that the NF-κB1 probe blocks DNA binding, whereas the SOX10 ligand increases SOX10-SOX10 interactions and disrupts melanoma transcriptional signaling. Our findings reveal heterogeneity in cysteine ligandability across cancers, pinpoint cell-intrinsic features driving cysteine targeting, and illustrate the use of covalent probes to disrupt oncogenic transcription-factor activity. [Display omitted] • Chemical proteomic analysis of cysteine ligandability across 400+ cancer cell lines • Ligandability is impacted by cellular redox states, protein conformations, and mutations • Covalent ligands disrupt activity of oncogenic transcription factors NF-κB1 and SOX10 DrugMap serves as a roadmap to develop covalent ligands for oncogenic drivers. [ABSTRACT FROM AUTHOR]

Objectives: Facial nerve decompression is a salvage treatment for Bell's palsy patients for whom a poor prognosis is anticipated with standard medical treatment. The transmastoid approach is a frequently performed approach, but it remains unknown if this surgery is effective when the ossicular chain is preserved. This study aimed to determine the efficacy of facial nerve decompression using the transmastoid approach in Bell's palsy. Design, setting and participants: This retrospective study included patients who had undergone transmastoid facial nerve decompression with ossicular chain preservation and patients who met the criteria for surgery, but received only medical treatment between January 2007 and May 2019, at a single centre. Main outcome measures: Attainment of House‐Brackmann grade I at 12 months after onset of facial palsy. Results: The recovery rate to House‐Brackmann grade I in the decompression group in the early phase (≤18 days after onset) was higher than that of the medical treatment group, although the difference was not significant (70% vs 47%, P =.160). However, within this early surgery group, a subgroup of cases with ≥95% facial nerve degeneration demonstrated a significant improvement in recovery rate (73% vs 30%, P =.018). Among surgeries performed in the late phase (≥19 days), only a subgroup with ≥95% facial nerve degeneration was available for analysis, and the difference in recovery rate was not significant compared with medical treatment alone (26% vs 30%, P = 1.00). Post‐surgical hearing evaluation demonstrated that average hearing deterioration was 1.3 dB which was non‐significant, suggesting this procedure does not cause hearing loss. Conclusions: Transmastoid facial nerve decompression with ossicular chain preservation in the early phase after symptom‐onset is an effective salvage treatment for severe Bell's palsy with ≥95% facial nerve degeneration. [ABSTRACT FROM AUTHOR]

• Photostability evaluated by chemiluminescence (CL). • Automatic evaluation system using CL and UV light source. • CL intensity time course was obtained for the first time. • Photo-OIT could be used for the evaluation of photo-stabilizers. An automatic evaluation system for photooxidation has been developed by utilizing a chemiluminescence apparatus combined with a light irradiation system. The system is composed of a controller, a driving device, and irradiation equipment, which are integrated with the chemiluminescence measurement system. Various measurement conditions can be set independently, including irradiation time (fixed or variable), waiting time from irradiation to measurement, chemiluminescence measurement time, number of repetitions (up to 999 times), and measurement temperature. LLDPEs containing Hindered Amine Light Stabilizers (HALS) and Ultraviolet Absorbers (UVA) were evaluated using this system. The decay of chemiluminescence after UV irradiation was repeatedly measured at r.t. and 105℃, respectively, below the melting point of LLDPE, and the time-course of chemiluminescence was obtained by plotting time against I(t = 0) for each instance. I(t = 0) represent the rate of photooxidation under UV exposure, calculated using second-order analysis of the chemiluminescence decay. The chemiluminescence intensity increased significantly in the initial stage with irradiation time, maintained a stable intensity for a period, and then exhibited a substantial increase in the later stage. We termed the point at which this significant increase in chemiluminescence occurs as the induction time of photooxidation (photo-OIT). Using this system, the photo-OIT of LLDPE samples with HALS and UVA was measured, revealing the potential for assessing the synergistic effects of photooxidation stabilizers. [ABSTRACT FROM AUTHOR]

Tunneling splittings in the water trimer have been determined by the semiclassical WKB method, based on pathways characterized at the computational level of second-order Mo\ller-Plesset theory with basis sets of aug-cc-pVTZ quality. This calculation takes into account the single-flip and bifurcation tunneling rearrangements of the water trimer. The predicted splittings are 37.93 cm-1 for the flip and 6.50×10-3 cm-1 for bifurcation, which agree quite well with the corresponding experimental values of 43.52 cm-1 and 9.63×10-3 cm-1. [ABSTRACT FROM AUTHOR]

Objective: Tinnitus is an auditory sensation that can cause discomfort or even pain. Because patients with tinnitus frequently have psychological problems, self-reporting of the severity of tinnitus is unreliable. We developed a new grading system and practical protocol for the systematic treatment of tinnitus that accounts for its severity, patients' psychological problems, and the frequency of catastrophic episodes. The aim of this study is to employ and validate the new system in patients with tinnitus.Methods: This study comprised two parts: (i) We identified 113 patients, who were then analyzed in terms of severity of tinnitus, psychological problems, and catastrophic episodes. They were then classified into 5 grades, and the records of their previous treatments were scrutinized. From these records, we designed a practical treatment protocol suitable for each of the 5 grades. (ii) We then identified 82 new patients, and graded and treated them according to the system developed in part (i). Patients were followed-up for at least 6 months; treatment efficacy was evaluated using the pre- and post-treatment scores on the Tinnitus Handicap Inventory (THI) and Hospital Anxiety and Depression Scale (HADS). Psychological status was also assessed with the DSM-IV.Results: (i) The overall patient group was categorized as follows: Grade I, 38 patients, average THI=37.6 points, average HADS=10.9 points, catastrophic episodes=0 points; Grade II, 24 patients, THI=70.6, HADS=13.1, catastrophic episodes=0; Grade III, 5 patients, THI=73.2, HADS=28.4, catastrophic episodes=0; Grade IV, 33 patients, THI=63.5, HADS=18.8, catastrophic episodes=1.0; Grade V, 13 patients, THI=73.2, HADS=22.4, catastrophic episodes=2.2. The treatment records revealed treatment via psychotropic drugs for 40% of Grade III, 45.5% of Grade IV, and 84.6% of Grade V patients; psychiatric consultation was provided for 20% of Grade III, 12.5% of Grade IV, and 53.8% of Grade V patients. (ii) THI scores improved significantly in Grades II, IV, and V after treatment using the new protocol; HADS scores improved significantly in Grades IV and V. Catastrophic episode scores improved significantly in Grades IV and V.Conclusion: We found large enough differences in THI and HADS scores to successfully classify patients with tinnitus into 5 distinct grades that accounted for tinnitus severity, psychological problems, and catastrophic episodes. We found significant improvements in tinnitus severity and psychological problems in the higher (more severe) grades when this system was used to guide treatment. This system not only provided a reasonably reliable categorization system, it simplified treatment without sacrificing efficacy. [ABSTRACT FROM AUTHOR]

In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2′–5′-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans -activation of innate immune response genes, including type I Interferon cytokines (IFN-I). Activation of the pro-inflammatory cGAS–STING–IRF3 response is triggered by direct recognition of the DNA genomes of bacteria and viruses, but also during RNA virus infection, neoplastic transformation, tumor immunotherapy and systemic auto-inflammatory diseases. In these circumstances, the source of immuno-stimulatory DNA has often represented a fundamental yet poorly understood aspect of the response. This review focuses on recent findings related to cGAS activation by an array of self-derived DNA substrates, including endogenous retroviral elements, mitochondrial DNA (mtDNA) and micronuclei generated as a result of genotoxic stress and DNA damage. These findings emphasize the role of the cGAS axis as a cell-intrinsic innate immune response to a wide variety of genomic insults. [ABSTRACT FROM AUTHOR]

The formation of molybdosilicate in the molybdate yellow method is elucidated by ESI-MS. Polymeric silicic acids were hydrolyzed to monomers, and molybdosilicates with a Keggin structure were formed. Each step of the formation reaction of molybdosilicate from molybdic and silicic acids between pH 1 and 2 was clarified by ESI-MS at the molecular level. In a solution below pH 0.5, the polymers of the molybdic acids were decomposed because of the high concentration of sulfuric acid. Excess sulfuric acid prevented the formation of molybdosilicate. Thus, none of the silicic acids reacted to form molybdosilicate at this pH, despite the presence of silicic acid and sulfate ions in the solution. Above pH 2, the condensation of molybdic acids occurred to form α-molybdosilicate. ESI-MS provides information on the formation of molybdosilicate and the individual reaction species present in the reaction mixture. [ABSTRACT FROM AUTHOR]

D300C is highly homologous with an inhibitory receptor CD300A in an immunoglobulin-like domain among the human CD300 family of paired immune receptors. To clarify the precise expression and function of CD300C, we generated antibodies discriminating between CD300A and CD300C, which recognized a unique epitope involving amino acid residues CD300A(F56-L57) and CD300C(L63-R64). Notably, CD300C was highly expressed in human monocytes and mast cells. Cross-linking of CD300C by its specific antibody caused cytokine/ chemokine production of human monocytes and mast cells. Fc receptor γ was indispensable for both efficient surface expression and activating functions of CD300C. To identify a ligand for CD300A or CD300C, we used reporter cell lines expressing a chimera receptor harboring extracellular CD300A or CD300C and intracellular CD3ζ, in which its unknown ligand induced GFP expression. Our results indicated that phosphatidylethanolamine (PE) among the lipids tested and apoptotic cells were possible ligands for both CD300C and CD300A. PE and apoptotic cells more strongly inducedGFPexpression in the reporter cells through binding to extracellular CD300A as compared with CD300C. Differential recognition of PE by extracellular CD300A and CD300C depended on different amino acid residues CD300A(F56-L57) and CD300C(L63-R64). Interestingly, GFP expression induced by extracellular CD300C-PE binding in the reporter cells was dampened by co-expression of full-length CD300A, indicating the predominance of CD300A over CD300C in PE recognition/signaling. PE consistently failed to stimulate cytokine production in monocytes expressing CD300C with CD300A. In conclusion, specific engagement of CD300C led to Fc receptor γ-dependent activation of mast cells and monocytes. [ABSTRACT FROM AUTHOR]

Abstract: A cDNA encoding an acyl-glucose-dependent anthocyanin 7-O-glucosyltransferase (AaAA7GT) was isolated from Agapanthus africanus petals; this is the first AAGT identified in a monocot. Peak expression of AaAA7GT in developing A. africanus petals occurred before the flowering stage, and was later than found previously for other anthocyanin biosynthetic genes. Analysis of recombinant proteins showed AaAA7GT had strict substrate preference for anthocyanidin 3-O-glycosides. The AaAA7GT amino acid had high sequence similarity to glycoside hydrolase family 1 (GH1) proteins, which typically act as β-glycosidases. A phylogenetic analysis of amino acid sequences suggested that AAGTs were derived from glycosidase early in the angiosperm lineage. [Copyright &y& Elsevier]

Leukocyte mono-Ig-like receptor 5 (LMIR5, also called CD300bJ is an activating receptor expressed in myeloid cells. We have previously demonstrated that T cell Ig mucin 1 works as a ligand for LMIR5 in mouse ischemia/reperfusion injury of the kidneys. In this article, we show that LMIR5 is implicated in LPS-induced sepsis in mice. Notably, neutrophils constitutively released a soluble form of LMIR5 (sLMIR5) through proteolytic cleavage of surface LMIR5. Stimulation with TLR agonists augmented the release of sLMIR5. LPS administration or peritonitis induction increased serum levels of sLMIR5 in mice, which was substantially inhibited by neutrophil depletion. Thus, neutrophils were the main source of LPS-induced sLMIR5 in vivo. On the other hand, i.p. administration of LMIR5-Fc, a surrogate of sLMIR5, bound to resident macrophages (M&phgr;) and stimulated transient inflammation in mice. Consistently, LMIR5-Fc induced in vitro cytokine production of peritoneal M&phgr; via its unknown ligand. Interestingly, LMIR5 deficiency profoundly reduced systemic cytokine production and septic mortality in LPS-administered mice, although it did not affect in vitro cytokine production of LPS-stimulated peritoneal M&phgr;. Importantly, the resistance of LMIR5-deficient mice to LPS- or peritonitis-induced septic death was decreased by LMIR5-Fc administration, implicating sLMIR5 in LPS responses in vivo. Collectively, neutrophil-derived sLMIR5 amplifies LPS-induced lethal inflammation. [ABSTRACT FROM AUTHOR]

A method employing capillary electrophoresis (CE) was developed to determine the rate constant of the very slow spontaneous dissociation of a complex species. The method uses a CE reactor (CER) to electrophoretically separate components from a complex zone and, thus, spontaneously dissociate a complex. The dissociation is accelerated by ligand substitution (LS) involving a competing ligand added to the electrophoretic buffer. The LS-CER method is validated using the dissociation of a Ti(IV)-catechin complex and EDTA as a competing ligand. There is good agreement between the spontaneous dissociation rate constant (kd = (1.64 ± 0.63) x 10-4 s-1) and the rate constant obtained by a conventional batchwise LS reaction Kd (1.43 ± 0.04) x 10-4 s-1). Furthermore, the usefulness of the method is demonstrated using a Ti(lV)-tiron complex, for which kd = (0.51 ± 0.43) x 10-4 s-1, corresponding to a half-life (t1/2) of 3.8 h. Notably, a single run of LS-CER for the Ti(PS) complex is completed within 40 min, implying that LS-CER requires a considerably shorter measurement time (roughly equal to t1/2) than conventional CER. LS-CER can be widely applied to determine the spontaneous dissociation rates of inorganic diagnostic and therapeutic reagents as well as of biomolecular complexes. [ABSTRACT FROM AUTHOR]

The vocal displays of male Indian peafowl ( Pavo cristatus) are thought to be sexually selected traits. To clarify the specific call types involved in breeding, as well as to provide basic information on the vocalisations of Indian peafowl, we conducted monthly daytime recordings in a large feral population in Japan. Based on 13,420 records, we identified seven different call types made only by males and six alarm calls uttered by both sexes. Furthermore, we found seasonal and diurnal changes in the calling activity of peafowl. Three of the male call types ( keow, ka and hoot-call) were particularly important for breeding, as sexually mature males produced them only during the breeding season, in a similar diurnal pattern to other breeding behaviours. A digital video image relating to the article is available at . [ABSTRACT FROM AUTHOR]

The elaborate train of male Indian peafowl, Pavo cristatus, is thought to have evolved in response to female mate choice and may be an indicator of good genes. The aim of this study was to investigate the role of the male train in mate choice using male- and female-centred observations in a feral population of Indian peafowl in Japan over 7 years. We found no evidence that peahens expressed any preference for peacocks with more elaborate trains (i.e. trains having more ocelli, a more symmetrical arrangement or a greater length), similar to other studies of galliforms showing that females disregard male plumage. Combined with previous results, our findings indicate that the peacock''s train (1) is not the universal target of female choice, (2) shows small variance among males across populations and (3) based on current physiological knowledge, does not appear to reliably reflect the male condition. We also found that some behavioural characteristics of peacocks during displays were largely affected by female behaviours and were spuriously correlated with male mating success. Although the male train and its direct display towards females seem necessary for successful reproduction, we conclude that peahens in this population are likely to exercise active choice based on cues other than the peacock''s train. [Copyright &y& Elsevier]

Uterine tumors detected after pelvic radiation therapy are rare. We report a case in which an endometrial tumor developed after pelvic radiation therapy for cervical cancer. The patient was a 70-year-old female with a history of pelvic radiotherapy for locally advanced cervical cancer. After 12 months of radiation therapy, magnetic resonance imaging showed tumors in the uterine cavity, and positron emission tomography-computed tomography showed no tumors, except uterine tumors. Since radiation therapy-induced cervical stenosis was conducted, endometrial examination could not be performed without anesthesia. As these tumors were detected after radiation therapy for uterine cancer, malignancy was considered. A laparoscopic-assisted transcervical hysteroscopic resection was performed for the diagnosis and treatment of uterine tumors after radiation therapy. This operative method was useful and enabled us to perform complete resection, observe the abdominal cavity, prepare for the possibility of secondary hysterectomy, and improve safety. [ABSTRACT FROM AUTHOR]

Uterine tumors detected after pelvic radiation therapy are rare. We report a case in which an endometrial tumor developed after pelvic radiation therapy for cervical cancer. The patient was a 70-year-old female with a history of pelvic radiotherapy for locally advanced cervical cancer. After 12 months of radiation therapy, magnetic resonance imaging showed tumors in the uterine cavity, and positron emission tomography-computed tomography showed no tumors, except uterine tumors. Since radiation therapy-induced cervical stenosis was conducted, endometrial examination could not be performed without anesthesia. As these tumors were detected after radiation therapy for uterine cancer, malignancy was considered. A laparoscopic-assisted transcervical hysteroscopic resection was performed for the diagnosis and treatment of uterine tumors after radiation therapy. This operative method was useful and enabled us to perform complete resection, observe the abdominal cavity, prepare for the possibility of secondary hysterectomy, and improve safety. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines in Japan for tinnitus were published in May 2019. Effective treatment of tinnitus contributes to quality of life and may improve depression, anxiety, and cognitive function. The highest priority of treatment recommended by this guideline involves educational counseling, including an explanation of the mechanisms of tinnitus. Understanding tinnitus pathology has also been reported to be a therapeutically effective educational counseling strategy. Further, explaining how sound therapy such as tinnitus retraining therapy (TRT) works is effective. Psychological and cognitive behavioral therapies may be an option. Here, the hearing aid is coupled with a sound generator in order to administer sound therapy for patients with more-severe symptoms. In Japan, it can be difficult to perform psychotherapy alongside otorhinolaryngology, and exemplary sound therapy is more likely to be carried out. In any case, the purpose of treatment is not to eliminate tinnitus, but rather reduce distress that manifests in response to tinnitus by promoting sensory adaptation. Clinically, the most important subject is not the loudness of tinnitus, but the severity of tinnitus distress. TRT consists of educational counseling and sound therapy. The tinnitus handicap inventory (THI) is used to measure the distress level for tinnitus and to determine treatment priorities. Rehabilitation of tinnitus is important because anxiety and depression are often observed in patients with severe tinnitus. Additionally, drug administration should be avoided. As a surgical treatment, a cochlear implant can affect tinnitus symptoms. It is essential to establish a treatment policy according to the disease condition and degree of distress. [ABSTRACT FROM AUTHOR]

The article reports on the findings of a study on the usability of fractal music as sound therapy in Tinnitus Retraining Therapy (TRT) treatment. The patients underwent standard TRT counseling based on the clinical guidelines outlined in the TRT directive counseling protocol. Case studies which illustrate the usefulness of fractal music as a sound therapy option within a TRT framework are presented.

Epithelioid leiomyoma of the vagina is extremely rare. Smooth muscle tumors of the vagina usually present with a submucosal growth pattern or a pedunculated growth pattern from the anterior vaginal wall into the vaginal cavity. Here we report a case of a 43-year-old woman with a solid epithelioid leiomyoma and a palpable mass in the pouch of Douglas. Transvaginal biopsy and angiography showed the epithelioid leiomyoma feeding from the vaginal artery behind the posterior vagina. An abdominal wide excision of the tumor with a partial vaginectomy was performed. Our use of ultrasound-guided needle biopsy and angiography was useful for preoperative diagnosis of a vaginal epithelioid leiomyoma exhibiting a pelvic mass. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study, which compared the effects of the WP9QY peptide on collagen-induced arthritis in mice with those of anti-tumor necrosis factor α (TNFα) monoclonal antibody. Excessive bone resorption at peripheral joints aggravate rheumatoid arthritis (RA), an inflammatory disease caused by autoimmune response. Several molecules that contribute to the clinical onset of RA, include cytokines, interleukin-1 (IL-1) and IL-16.

When humans repeatedly use a tool, our body image alters until the tool finally becomes a part or an extension of the body. This alteration of body image perhaps results from re-integration of somatosensory and visual signals. We trained Japanese monkeys to use a rake-shaped tool to retrieve a distant food pellet, then used a novel tissue-sampling method to suction brain tissue from the anterior bank of their intraparietal sulcus, where somatosensory and visual signals converge. Examination of the messenger RNA expression levels of neurotrophins and their receptors using real-time quantitative polymerase chain reaction revealed learning-selective induction in the expression of brain-derived neurotrophic factor, its receptor trkB, and NT-3 during, but not after, the learning. These results suggest that these factors are involved in the reorganization of the somatosensory and visual signals in the anterior bank of the intraparietal sulcus when monkeys are learning the use of the tool. [Copyright &y& Elsevier]

Photooxidation of polypropylene (PP) was investigated by chemiluminescence (CL) after UV irradiation of main wavelengths of 254 nm and 365 nm in air at an ambient temperature. From the kinetic analysis of CL intensity change just after irradiation, CL intensity at the time of the cessation of UV irradiation, (I(t=0)), was obtained. The irradiation time dependence of I(t=0) gave a time-course, where the CL intensity increased with time in the first stage and reached a steady state, and after maintaining the same level for a while, it largely increased in the later stage. The steady state intensity, which is considered the rate of peroxy radical formation, was found to be dependent on the crystallinity of PP. The lower the crystallinity is, the higher the steady state intensity is, indicating the preferential photoinitiation reaction to occur in the amorphous phase. The isothermal CL measurement at above the melting point of the samples, which were stored at 25 °C for various periods after UV irradiation, suggests that there are two types of CL emitting sources of different lifetimes; one is quenched in about one day and the other survives for more than 10 days. The temperature rising measurement also indicates the existence of two types of CL emitting sources, too. Further, thermal oxidation before UV irradiation was found to clearly promote the photooxidation. In contrast, thermal oxidation in oxygen was increasingly accelerated by the pre-photooxidation. Irradiation time dependence of CL intensity for PP calculated from the data of Fig. 2(b) in th text. Irradiation of 254 nm UV and the CL measurement were carried out at 20 °C in air. [Display omitted] [ABSTRACT FROM AUTHOR]

To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment. Multi-institutional prospective single-arm observational study. Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan. The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society—A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA). Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P =.0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P =.0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement. HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family. [ABSTRACT FROM AUTHOR]

This article focuses on electrode impedance with and without electrode positioner in Clarion device. The Clarion cochlear implant system was at first approved with the electrode positioning system (EPS). The Clarion electrode array is originally pre-curved in shape and, in addition, EPS is to move the array closer to the medial wall in the scala tympani. It is theoretically advantageous that the implanted electrodes are as close as possible to the modiolus. EPS theoretically seems to bring better hearing outcome and language development.

Learning but not execution of tool-use induced expression of brain-derived neurotrophic factor (BDNF). The expression was highest in the anterior bank of the intraparietal sulcus, especially in the region posteriorly adjacent to the somatosensory shoulder and forearm region in area 3b, suggesting that BDNF plays a role in altering the body image of the hand to include the repeatedly used tool as its extension. [Copyright &y& Elsevier]

Objective: Intellectual disability (ID) and autism spectrum disorder (ASD) are common among children who are candidates for cochlear implants. However, the implications of these comorbidities for cochlear implant placement have been not fully established. This study sought to identify these implications by comparing developmental delays among children with these conditions.Methods: Participants were children who were followed up at least every 6 months for 24 months after cochlear implant surgery. Developmental delays were assessed using the Enjoji Scale of Infant Analytical Development (Enjoji Scale) and compared in three groups with hearing loss: those with ID (ID group, n=4); those with ASD and ID (ASD+ID group, n=4); and those with typical development (control group, n=5). Developmental delay was evaluated longitudinally before and after cochlear implant placement for 18 months.Results: Among the six subscales that make up the Enjoji Scale, language development and intelligence development were significantly delayed in all three groups and were exacerbated over time except for language development in the control group. Emotional development and social behavior were significantly delayed only in the ASD+ID group. Comparison of intergroup differences revealed delays in language development in the ID and ASD+ID groups compared with the control group.Conclusion: The Enjoji Scale successfully demonstrated developmental delays characteristic to the underlying comorbidities of ID with or without ASD in children with cochlear implants. The Enjoji Scale can be a useful diagnostic tool for screening children with cochlear implants for ID with or without ASD. [ABSTRACT FROM AUTHOR]

Multiple anticancer drugs have been proposed to cause cell death, in part, by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs, exactly how the resultant ROS function and are sensed is poorly understood. It remains unclear which proteins the ROS modify and their roles in drug sensitivity/resistance. To answer these questions, we examined 11 anticancer drugs with an integrated proteogenomic approach identifying not only many unique targets but also shared ones—including ribosomal components, suggesting common mechanisms by which drugs regulate translation. We focus on CHK1 that we find is a nuclear H 2 O 2 sensor that launches a cellular program to dampen ROS. CHK1 phosphorylates the mitochondrial DNA-binding protein SSBP1 to prevent its mitochondrial localization, which in turn decreases nuclear H 2 O 2. Our results reveal a druggable nucleus-to-mitochondria ROS-sensing pathway—required to resolve nuclear H 2 O 2 accumulation and mediate resistance to platinum-based agents in ovarian cancers. [Display omitted] • Integrated chemical proteomics and CRISPRi screens identify ROS-target proteins • Nuclear H 2 O 2 oxidizes C408 in CHK1's autoinhibitory domain leading to its activation • CHK1 regulates mitochondrial translation by inhibiting mtDNA-binding protein SSBP1 • SSBP1 promotes resistance to platinum-based agents and nuclear H 2 O 2 in ovarian cancers Anticancer drug mechanism studies using an integrated proteogenomic framework reveal a nucleus-to-mitochondria ROS-sensing pathway that couples DNA damage response to the control of mitochondrial translation and may serve as a mechanism of resistance to platinum-based agents. [ABSTRACT FROM AUTHOR]

Objective: To determine the prognostic factors for hearing recovery in patients with sudden sensorineural hearing loss (SSHL) refractory to systemic corticosteroids following salvage treatment.Methods: This is a retrospective observational study at nine tertiary referral hospitals. A total of 120 patients with sudden deafness refractory to systemic corticosteroids were enrolled. The patients were randomly assigned to receive topical application of recombinant human IGF-1 or intratympanic injection of dexamethasone as salvage treatment. Multiple regression analysis was performed to identify determinants of hearing recovery using pure tone audiometry results at 8 weeks after treatment. Clinical predictors that were evaluated included age, sex, pretreatment hearing level, presence of vertiginous symptoms, days to study entry from symptom onset and salvage treatment assignment (IGF-1 vs. dexamethasone).Results: The linear regression model identified age (P=0.001), pretreatment hearing level (P<0.001), days to study entry from symptom onset (P=0.011) and treatment assignment (P=0.033) at 8 weeks after treatment as significant variables influencing the recovery of pure tone audiometry average thresholds. Younger age (<60 years), early initiation of salvage treatment and treatment with topical IGF-1 therapy had significant effects on hearing recovery.Conclusion: The results indicate that early initiation and choice of treatment modalities for salvage treatment may be important for the prognosis of patients with refractory SSHL. The positive effect of topical IGF-1 therapy on hearing recovery indicates its utility as salvage treatment. [ABSTRACT FROM AUTHOR]

Juvenile myelomonocytic leukemia (JMML) is an intractable pediatric leukemia with poor prognosis whose molecular pathogenesis is poorly understood, except for somatic or germline mutations of RAS pathway genes, including PTPN11, NF1, NRAS, KRAS and CBL, in the majority of cases. To obtain a complete registry of gene mutations in JMML, whole-exome sequencing was performed for paired tumor-normal DNA from 13 individuals with JMML (cases), which was followed by deep sequencing of 8 target genes in 92 tumor samples. JMML was characterized by a paucity of gene mutations (0.85 non-silent mutations per sample) with somatic or germline RAS pathway involvement in 82 cases (89%). The SETBP1 and JAK3 genes were among common targets for secondary mutations. Mutations in the latter were often subclonal and may be involved in the progression rather than the initiation of leukemia, and these mutations associated with poor clinical outcome. Our findings provide new insights into the pathogenesis and progression of JMML. [ABSTRACT FROM AUTHOR]

Here we report whole-exome sequencing of individuals with various myeloid malignancies and identify recurrent somatic mutations in SETBP1, consistent with a recent report on atypical chronic myeloid leukemia (aCML). Closely positioned somatic SETBP1 mutations encoding changes in Asp868, Ser869, Gly870, Ile871 and Asp880, which match germline mutations in Schinzel-Giedion syndrome (SGS), were detected in 17% of secondary acute myeloid leukemias (sAML) and 15% of chronic myelomonocytic leukemia (CMML) cases. These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology. Mutant cases were associated with advanced age and monosomy 7/deletion 7q (-7/del(7q)) constituting poor prognostic factors. Analysis of serially collected samples indicated that SETBP1 mutations were acquired during leukemic evolution. Transduction with mutant Setbp1 led to the immortalization of mouse myeloid progenitors that showed enhanced proliferative capacity compared to cells transduced with wild-type Setbp1. Somatic mutations of SETBP1 seem to cause gain of function, are associated with myeloid leukemic transformation and convey poor prognosis in myelodysplastic syndromes (MDS) and CMML. [ABSTRACT FROM AUTHOR]

Conclusion: The Japanese version of the Tinnitus Handicap Inventory-12 (THI-12), Tinnitus Rating Scale (TRS), TRS 1-week version (TRSw), Tinnitus Severity Scale (TSS), and TSS 1-week version (TSSw), which were developed in this study, showed high reliability and validity, suggesting their usefulness in clinical practice. Based on the THI severity grades, we propose that the severity grades of THI-12 (draft) are categorized into four groups: 0-4 points, 5-9 points, 10-14 points, and 15-24 points. Objectives: We developed Japanese versions of new questionnaires for evaluating the level of psychological distress and difficulty in activities of daily living due to tinnitus, and performed their psychometric validation to determine the reliability and validity. The THI-12 is an assessment consisting of 12 items, each of which is rated on a 3-point scale that was created by reducing the number of questions from the 25 items of the THI. The TRS, TRSw, TSS, and TSSw, which were self-evaluation questionnaires of tinnitus on an 11-grade integer Likert scale from 0 to 10 points, were used as additional instruments to assess tinnitus severity and distress. Methods: The subjects were healthy adults, and patients with subjective tinnitus who were examined at the Otolaryngology Department of Keio University Hospital, Osaka City University Hospital, or Nagoya City University Hospital with a chief complaint of tinnitus between September 2010 and January 2011. In all, 38 healthy adult subjects and 113 patients with subjective tinnitus were included. We examined the reproducibility and the internal consistency for reliability. We also examined the relationship with the available scales (THI and Hospital Anxiety and Depression Scale, HADS) and group divergence for validity. Results: The psychometric validation showed high reliability and validity of the THI-12, TRS, TRSw, TSS, and TSSw. [ABSTRACT FROM AUTHOR]

Conclusion: The Japanese version of the Tinnitus Handicap Inventory-12 (THI-12), Tinnitus Rating Scale (TRS), TRS 1-week version (TRSw), Tinnitus Severity Scale (TSS), and TSS 1-week version (TSSw), which were developed in this study, showed high reliability and validity, suggesting their usefulness in clinical practice. Based on the THI severity grades, we propose that the severity grades of THI-12 (draft) are categorized into four groups: 0-4 points, 5-9 points, 10-14 points, and 15-24 points. Objectives: We developed Japanese versions of new questionnaires for evaluating the level of psychological distress and difficulty in activities of daily living due to tinnitus, and performed their psychometric validation to determine the reliability and validity. The THI-12 is an assessment consisting of 12 items, each of which is rated on a 3-point scale that was created by reducing the number of questions from the 25 items of the THI. The TRS, TRSw, TSS, and TSSw, which were self-evaluation questionnaires of tinnitus on an 11-grade integer Likert scale from 0 to 10 points, were used as additional instruments to assess tinnitus severity and distress. Methods: The subjects were healthy adults, and patients with subjective tinnitus who were examined at the Otolaryngology Department of Keio University Hospital, Osaka City University Hospital, or Nagoya City University Hospital with a chief complaint of tinnitus between September 2010 and January 2011. In all, 38 healthy adult subjects and 113 patients with subjective tinnitus were included. We examined the reproducibility and the internal consistency for reliability. We also examined the relationship with the available scales (THI and Hospital Anxiety and Depression Scale, HADS) and group divergence for validity. Results: The psychometric validation showed high reliability and validity of the THI-12, TRS, TRSw, TSS, and TSSw. [ABSTRACT FROM AUTHOR]

Summary: Mast cells (MCs) are key effector cells in allergic reactions. However, the inhibitory mechanism that prevents excessive activation of MCs remains elusive. Here we show that leukocyte mono-immunoglobulin-like receptor 3 (LMIR3; also called CD300f) is a negative regulator of MC activation in vivo. LMIR3 deficiency exacerbated MC-dependent allergic responses in mice, including anaphylaxis, airway inflammation, and dermatitis. Both physical binding and functional reporter assays via an extracellular domain of LMIR3 showed that several extracellular lipids (including ceramide) and lipoproteins were possible ligands for LMIR3. Importantly, MCs were frequently surrounded by extracellular ceramide in vivo. Upon engagement of high-affinity immunoglobulin E receptor, extracellular ceramide-LMIR3 binding inhibited MC activation via immunoreceptor tyrosine-based inhibitory and switch motifs of LMIR3. Moreover, pretreatment with LMIR3-Fc fusion protein or antibody against either ceramide or LMIR3 interfered with this binding in vivo, thereby exacerbating passive cutaneous anaphylaxis. Thus, the interaction between extracellular ceramide and LMIR3 suppressed MC-dependent allergic responses. [ABSTRACT FROM AUTHOR]

Here we characterize leukocyte mono-Ig-like receptor 7 (LMIR7)/CLM-3 and compare it with an activating receptor, LMIR4/CLM-5, that is a counterpart of an inhibitory receptor LMIR3/CLM-1. LMIR7 shares high homology with LMIR4 in the amino acid sequences of its Ig-like and transmembrane domains. Flow cytometric analysis demonstrated that LMIR4 was predominantly expressed in neutrophils, whereas LMIR7 was highly expressed in mast cells and monocytes/macrophages. Importantly, LMIR7 engagement induced cytokine production in bone marrow-derived mast cells (BMMCs). Although FcRγ deficiency did not affect surface expression levels of LMIR7, it abolished LMIR7-mediated activation of BMMCs. Consistently we found significant interaction of LMIR7-FcRγ, albeit with lower affinity compared with that of LMIR4-FcRγ. Our results showed that LMIR7 transmits an activating signal through interaction with FcRγ. In addition, like LMIR4, LMIR7 synergizes with TLR4 in signaling. Analysis of several chimera receptors composed of LMIR4 and LMIR7 revealed these findings: 1) the transmembrane of LMIR7 with no charged residues maintained its surface expression at high levels in the absence of FcRγ, 2) the extracellular juxtamembrane region of LMIR7 had a negative effect on its surface expression levels; and 3) the strong interaction of LMIR4 with FcRγ depended on the extracellular juxtamembrane region as well as the transmembrane domain of LMIR4. Thus, LMIR7 shares similarities with LMIR4, although they are differentially regulated in their distribution, expression, and function. [ABSTRACT FROM AUTHOR]

We developed a cochlear nerve action potential (CNAP) monitoring technique using a microdissector and compared the results of CNAP and auditory brainstem response (ABR) monitoring. Thirty-six patients underwent vestibular schwannoma resection via the retrosigmoid approach to preserve hearing. Both CNAP with the microdissector and surface ABR were recorded during the operation. We used the microdissector as an intracranial electrode for CNAP monitoring. The CNAP waveform was classified into four types: triphasic, biphasic, positive, and flat. At the completion of the tumor resection, the triphasic waveform was observed in 11 patients and the biphasic waveform was observed in 11 patients. Hearing function was preserved in all of them, although it was preserved in only two patients with other CNAP waveform types. The prognostic value of CNAP is significantly higher than that of ABR. We found that although CNAP with a microdissector does not provide real-time monitoring, with the classification of waveforms it can be used as predictable tool for postoperative hearing more accurately than ABR. [ABSTRACT FROM AUTHOR]

Activating receptor activator of NF-kappaB (RANK) and TNF receptor (TNFR) promote osteoclast differentiation. A critical ligand contact site on the TNFR is partly conserved in RANK. Surface plasmon resonance studies showed that a peptide (WP9QY) that mimics this TNFR contact site and inhibits TNF-alpha-induced activity bound to RANK ligand (RANKL). Changing a single residue predicted to play an important role in the interaction reduced the binding significantly. WP9QY, but not the altered control peptide, inhibited the RANKL-induced activation of RANK-dependent signaling in RAW 264.7 cells but had no effect on M-CSF-induced activation of some of the same signaling events. WP9QY but not the control peptide also prevented RANKL-induced bone resorption and osteoclastogenesis, even when TNFRs were absent or blocked. In vivo, where both RANKL and TNF-alpha promote osteoclastogenesis, osteoclast activity, and bone loss, WP9QY prevented the increased osteoclastogenesis and bone loss induced in mice by ovariectomy or low dietary calcium, in the latter case in both wild-type and TNFR double-knockout mice. These results suggest that a peptide that mimics a TNFR ligand contact site blocks bone resorption by interfering with recruitment and activation of osteoclasts by both RANKL and TNF. [ABSTRACT FROM AUTHOR]