Improvements in blood IGF-1 and skeletal age following adenotonsillectomy for growth delay in children with obstructive sleep apnea.

OBJECTIVE: In children with obstructive sleep apnea (OSA) who underwent adenotonsillectomy (AT), we measured body height and weight using standard deviation (SD) scores, insulin-like growth factor 1 (IGF-1), and skeletal age using carpal radiography. We then compared these values before and after surgery with the aim of investigating postoperative improvements in growth hormone (GH) deficiency. METHODS: Subjects comprised 35 children between 2 and 9 years of age (21 boys, 14 girls; mean age, 5.85 ± 1.75 years). Respiratory event index (REI), 3 % oxygen desaturation index (3 % ODI), height SD score, body mass index (BMI) percentile, blood IGF-1 level, and skeletal age from carpal radiographs were measured before surgery and both 3 and 12 months after surgery, and compared. RESULTS: Height SD score improved significantly from preoperatively (-0.44 ± 1.13) to both 3 months postoperatively (-0.22 ± 1.14) and 12 months postoperatively (-0.13 ± 0.94). However, no significant improvement in height SD score was seen from 3 months to 12 months after AT. BMI percentile improved significantly from preoperatively (35.6 ± 26.7) to both 3 months postoperatively (44.7 ± 26.5) and 12 months postoperatively (49.1 ± 22.15), with significant improvement also seen from 3 months to 12 months after AT. SD score for IGF-1 showed significant improvement from before (-0.57 ± 1.00) to 12 months after surgery (-0.12 ± 0.89). No significant improvement in the difference between skeletal and chronological ages was seen from before to after surgery, but the number of patients for whom skeletal age normalized from before to after surgery increased significantly (74.3 % vs. 94.3 %), and the number with advanced or delayed skeletal age decreased significantly (25.7 % vs. 5.7 %) CONCLUSION: Early improvements can be obtained with surgical treatment in children with OSA who have short height and poor weight gain due to GH deficiency.

Dataset dependency of low-density lipoprotein-cholesterol estimation by machine learning.

OBJECTIVES: We evaluated the applicability of a machine learning-based low-density lipoprotein-cholesterol (LDL-C) estimation method and the influence of the characteristics of the training datasets. METHODS: Three training datasets were chosen from training datasets: health check-up participants at the Resource Center for Health Science (N = 2664), clinical patients at Gifu University Hospital (N = 7409), and clinical patients at Fujita Health University Hospital (N = 14,842). Nine different machine learning models were constructed through hyperparameter tuning and 10-fold cross-validation. Another test dataset of another 3711 clinical patients at Fujita Health University Hospital was selected as the test set used for comparing and validating the model against the Friedewald formula and the Martin method. RESULTS: The coefficients of determination of the models trained on the health check-up dataset produced coefficients of determination that were equal to or inferior to those of the Martin method. In contrast, the coefficients of determination of several models trained on clinical patients exceeded those of the Martin method. The means of the differences and the convergences to the direct method were higher for the models trained on the clinical patients' dataset than for those trained on the health check-up participants' dataset. The models trained on the latter dataset tended to overestimate the 2019 ESC/EAS Guideline for LDL-cholesterol classification. CONCLUSION: Although machine learning models provide valuable method for LDL-C estimates, they should be trained on datasets with matched characteristics. The versatility of machine learning methods is another important consideration.

Validation of the Martin method to estimate low-density lipoprotein cholesterol concentrations in Japanese populations and a modified method for laboratory information system application.

OBJECTIVES: High concentrations of low-density lipoprotein cholesterol (LDL-C) are a risk factor for cardiovascular disease. We validated the efficacy of the Martin method is useful in the estimation of LDL-C concentrations was validated in Japanese populations and derived a modified Martin method for easy laboratory information system applications. METHODS: We created 3 subject groups, including 2664 health check-up participants registered with the Resource Center for Health Science, 29,806 clinical patients (A) in the Gifu University Hospital, and 113,716 clinical patients (B) in the Fujita Health University Hospital. Each method to estimate serum LDL-C concentrations (Friedewald formula, Martin method and modified Martin method) was validated by correlation analysis with serum LDL-C concentrations measured using a direct method. RESULTS: The correlation coefficients with the direct method in terms of the Friedewald formula, Martin method, and modified Martin method were 0.963, 0.972 and 0.970 in the health check-up participants; 0.946, 0.962 and 0.961 in clinical patients A; and 0.961, 0.979 and 0.978 in clinical patients B, respectively. Concordance ratios with using the direct method in the Friedewald formula, Martin method and modified Martin method were 82.8%, 85.5% and 85.3% in the health check-up participants; 76.4%, 80.5% and 80.2% in clinical patients A; and 76.1%, 82.6% and 82.6% in clinical patients B, respectively. CONCLUSION: Our results show that the Martin and modified Martin methods display good performance in terms of the estimation of LDL-C concentrations among triglyceride concentrations of a wide range, and they may thus be useful for estimating LDL-C concentrations.

Preliminary Clinical Trial of Biomarkers to Predict Response to Sublingual Immunotherapy for Japanese Cedar Pollinosis.

BACKGROUND: As part of the planning for a future multicenter study, this preliminary clinical trial used serum samples from patients to identify biomarkers for predicting the therapeutic effects of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis (JCP). METHODS: This prospective study included patients undergoing SLIT for JCP at our hospital. All enrolled patients (N = 17) started SLIT between June and November of 2015. With informed consent from the patients, blood samples were obtained in January, March, and June of 2016, and patients completed the Japan rhino-conjunctivitis quality of life questionnaire (JRQLQ). On the basis of the JRQLQ results, the 6 patients with the best outcomes were included in the high-response group (HRG), and the 5 patients with the worst outcomes were included in the poor-response group (PRG). We then compared serum data between the two groups, to identify useful biomarkers. RESULTS: IL-12p70 and VEGF levels tended to be higher in the HRG than in the PRG in January, March, and June (0.10 > p > 0.05). In addition, the June IL-17 level was significantly higher (p < 0.05) in the HRG than in the PRG. CONCLUSIONS: IL-12p70 and VEGF may be useful biomarkers for predicting the effects of SLIT. In addition, although IL-17 does not appear to be useful as a biomarker for evaluating treatment response at the start of SLIT, it may be useful as a biomarker after the beginning phase of SLIT.

Novel method for mass producing genetically sterile fish from surrogate broodstock via spermatogonial transplantation†.

A stable system for producing sterile domesticated fish is required to prevent genetic contamination to native populations caused by aquaculture escapees. The objective of this study was to develop a system to mass produce stock for aquaculture that is genetically sterile by surrogate broodstock via spermatogonial transplantation (SGTP). We previously discovered that female medaka carrying mutations on the follicle-stimulating hormone receptor (fshr) gene become sterile. In this study, we demonstrated that sterile hybrid recipient females that received spermatogonia isolated from sex-reversed XX males (fshr (-/-)) recovered their fertility and produced only donor-derived fshr (-) X eggs. Natural mating between these females and fshr (-/-) sex-reversed XX males successfully produced large numbers of sterile fshr (-/-) female offspring. In conclusion, we established a new strategy for efficient mass production of sterile fish. This system can be applied to any aquaculture species for which SGTP and methods for producing sterile recipients can be established.

Anti-Inflammatory Effects of EM900 on Cultured Human Nasal Epithelial Cells.

OBJECTIVES: Macrolide therapy is an important conservative therapy for chronic rhinosinusitis, especially in Japan. The mechanism underlying this therapy involves anti-inflammatory and not antimicrobial activity. However, the administration of long-term low-dose macrolides (LTLMs) causes an increase in the number of antibiotic-resistant bacteria. EM900 is a derivative of erythromycin (EM), with anti-inflammatory but not antibacterial effects. It does not induce macrolide-resistant bacteria as shown by LTLM. In the present study, we analyzed the inhibitory effects of EM900 in comparison with those of clarithromycin (CAM) on inflammatory cytokine production in human nasal epithelial cells (HNEpCs). METHODS: After HNEpCs were cultured for 4 days, CAM or EM900 was added into the culture, followed by stimulation with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) levels were measured using real-time polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). RESULTS: Both the ELISA and RT-PCR showed that EM900 and CAM significantly inhibited IL-8 production in HNEpCs. In contrast, EM900 and CAM did not suppress the increased VEGF production when HNEpCs were stimulated with TNF-α. CONCLUSION: EM900 showed an anti-inflammatory effect, such as that of CAM, due to the inhibitory effect on IL-8 production in HNEpCs.

Relationship between swallowing function and breathing/phonation.

OBJECTIVE: Clarification of the association between the swallowing function and respiratory and phonatory functions. METHODS: The subjects were 30 patients with a chief complaint of swallowing disorder with clear consciousness capable of retaining a sitting position. Patients with organic and functional diseases of the larynx were excluded. Twenty-two and eight patients were male and female, respectively, and the mean age was 77.0±14.6years old. The chest expansion score was measured as an index of the respiratory function, and the maximum phonation time (MPT) was measured as an index of the phonatory function. The presence or absence of aspiration was judged using videoendoscopic swallowing study (VESS) and videofluoroscopic swallow studies (VFSS). The patients were divided into those with and without aspiration, and the chest expansion score and MPT were compared. In addition, the distance of laryngeal elevation was measured in the lateral view of VFSS, and its correlations with the chest expansion score and MPT were closely analyzed. To evaluate reliability of the test, the distance of laryngeal elevation and videoendoscopic score were compared between the presence and absence of aspiration. RESULTS: The distance of laryngeal elevation was significantly shortened and the videoendoscopic score was significantly higher in the group with aspiration, as previously reported. On comparison of the chest expansion score between the groups with and without aspiration, no significant difference was noted at the axillary or xiphoid process level, and shortening was significant only at the 10th rib level in the group with aspiration. On comparison of MPT, it was significantly shortened in the group with aspiration. In addition, a significant positive correlation with the distance of laryngeal elevation was noted in both chest expansion score and MPT. CONCLUSION: It was suggested that declines of the respiratory and phonatory functions are risk factors of aspiration through limiting laryngeal elevation, and the chest expansion score at the 10th rib level and MPT are useful for screening of aspiration.

Production of the medaka derived from vitrified whole testes by germ cell transplantation.

The medaka (Oryzias latipes) is a teleost model distinguished from other model organisms by the presence of inbred strains, wild stocks, and related species. Cryopreservation guarantees preservation of these unique biological resources. However, because of their large size, cryopreservation techniques for their eggs and embryos have not been established. In the present study, we established a methodology to produce functional gametes from cryopreserved testicular cells (TCs). Whole testes taken from medaka were cryopreserved by vitrification. After thawing, the cells dissociated from cryopreserved testicular tissues were intraperitoneally transplanted into sterile triploid hatchlings. Some cells, presumably spermatogonial stem cells, migrated into the genital ridges of recipients and resulted in the production of eggs or sperm, based on sex of the recipient. Mating of recipients resulted in successful production of cryopreserved TC-derived offspring. We successfully produced individuals from the Kaga inbred line, an endangered wild population in Tokyo, and a sub-fertile mutant (wnt4b-/-) from cryopreserved their TCs. This methodology facilitates semi-permanent preservation of various medaka strains.

[EFFECT OF PROPHYLACTIC TREATMENT BY LEUKOTORIENE RECEPTOR ANTAGONIST ON JAPANESE CEDAR POLLINOSIS OF PRE- AND POST-SCHOOL CHILDREN JAPANESE CEDAR POLLINOSIS].

UNLABELLED: Backgroud: It has already been reported that the prophylactic treatment by leukotoriene receptor antagonists is more effective on reducing symptoms of Japanese cedar pollinosis than the authentic treatment after the pollen dispersal. However, the treatment above has never evaluated in children cases around school age in ENT out-patient clinic. This study about the prophylactic treatment was planned to focus on the effect in the generation of pre- and post-elementary school entrance. METHODS: Children of pre- and post-elementary school entrance were enrolled for this study. This study was achieved in seasons of Japanese cedar pollinosis both in 2013 and 2014, and was designed as the comparison of clinical symptoms and quality of life in between two such groups as one group with the prophylactic treatment and another with the authentic treatment. RESULTS: Efficacy of prophylactic treatment by leukotoriene receptor antagonists was elucidated as follows; quality of sleep was significantly better both in 2013 and 2014, and more kinds of clinical symptoms or quality of life impairments were significantly more suppressed than in the group with the authentic treatment in 2014 when less pollen was dispersed. CONCLUSION: Even in the children of pre- and post-elementary school entrance, the prophylactic treatment by leukotoriene receptor antagonists is more effective on reducing symptoms of Japanese cedar pollinosis than the authentic treatment.

Solitary fibrous tumor arising from the superior nasal turbinate: a case report.

Solitary fibrous tumor is a rare neoplasm, which was first described as a primary spindle-cell tumor of the pleura, is a type of mesenchymal tumor. Although the majority of these tumors originate in the pleura, they can also derive from extrapleural sites, such as the liver, lung, abdomen, and extremities. We report a rare case of a nasal solitary fibrous tumor that originated from the nasal superior turbinate. The tumor, measuring 45 × 25 × 10 mm, was in the right nasal cavity. We successfully removed the tumor in one piece through endonasal endoscopic surgery. The tumor had spindle-shaped cells within a collagenous stroma and was positive for CD34. There has been no evidence of tumor recurrence in the 14 months following surgery.

Rapid rehydration and moderate plasma glucose elevation by fluid containing enzymatically synthesized glycogen.

Enzymatically synthesized glycogen (ESG) has high solubility and its solution has low osmotic pressure. Therefore ESG solution could be rapidly absorbed and could be adequate for water rehydration and carbohydrate supplementation during exercise. The object of this study was to evaluate the gastric emptying time and plasma glucose elevation after an administration of ESG solution in comparison with another carbohydrate solution by using a laboratory animal. Male BALB/c mice were administered 10% w/v solution of glucose, maltodextrin, starch, naturally synthesized glycogen (NSG) and ESG at a dose of 20 µL/g body weight for the measurement of gastric emptying rate (Experiment 1) and 10 µL/g body weight for the measurement of plasma glucose elevation (Experiment 2). The osmolarity of gastric content was lower in the ESG and maltodextrin group than the other carbohydrate group. Weight of gastric fluid was significantly lower in the ESG and water group than the glucose group (p<0.01). Plasma glucose level was significantly lower in the ESG group than the glucose group from 0 to 60 min after administration (p<0.01), whereas plasma glucose level was same from 60 to 120 min for the ESG and glucose group (p=0.948). In Experiment 3, BALB/c mice ran on a treadmill for 2 h and were administered 8% of ESG or glucose solution (1.75, 3.5 or 7.0 µL/g body weight) every 20 min during running. There was no difference in post-exercise muscle glycogen level. These data suggest that 1) ESG beverage does not disturb water absorption because of its short gastric emptying time and 2) ESG slowly elevates plasma glucose level and maintains it for a prolonged time compared to the glucose solution.

Expression for caffeine biosynthesis and related enzymes in Camellia sinensis.

Caffeine (1,3,7-trimethylxanthine) is a purine alkaloid that is present in high concentrations in the tea plant Camellia sinensis. Caffeine synthase (CS, EC 2.1.1.160) catalyzes the S-adenosyl-L-methionine-dependent N-3- and N-1-methylation of the purine base to form caffeine, the last step in the purine alkaloid biosynthetic pathway. We studied the expression profile of the tea caffeine synthase (TCS) gene in developing leaves and flowers by means of northern blot analysis, and compared it with those of phenylalanine ammonia lyase (PAL, EC 4.3.1.5), chalcone synthase (CHS, EC 2.3.1.74), and S-adenosyl-L-methionine synthase (SAMS, EC 2.5.1.6). The amount of TCS transcripts was highest in young leaves and declined markedly during leaf development, whereas it remained constant throughout the development of the flower. Environmental stresses other than heavy metal stress and plant hormone treatments had no effect on the expression of TCS genes, unlike the other three genes. Drought stress suppressed TCS gene expression in leaves, and the expression pattern mirrored that of the dehydrin gene. The amounts of TCS transcripts increased slightly on supply of a nitrogen source. We discuss the regulation of TCS gene expression.

Occurrence of theobromine synthase genes in purine alkaloid-free species of Camellia plants.

Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are purine alkaloids that are present in high concentrations in plants of some species of Camellia. However, most members of the genus Camellia contain no purine alkaloids. Tracer experiments using [8-(14)C]adenine and [8-(14)C]theobromine showed that the purine alkaloid pathway is not fully functional in leaves of purine alkaloid-free species. In five species of purine alkaloid-free Camellia plants, sufficient evidence was obtained to show the occurrence of genes that are homologous to caffeine synthase. Recombinant enzymes derived from purine alkaloid-free species showed only theobromine synthase activity. Unlike the caffeine synthase gene, these genes were expressed more strongly in mature tissue than in young tissue.