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Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (P FDR ) < 0.001), IL-9 (56.64, 20.46 to 92.82, P FDR  < 0.001) and MIP-1b (18.27, 4.96 to 31.57, P FDR  < 0.001) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (P FDR  < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = -0.05, -0.10 to 0.003, P = 0.067; IL-9: -0.01, -0.02 to -0.003, P = 0.005; MIP-1b: -0.02, -0.04 to -0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed. Trial registration: UMIN000015264, NCT03466671/UMIN000031412., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The semidry dot-blot method is a diagnostic procedure for detecting lymph node (LN) metastases using the presence of cytokeratin (CK) in lavage fluid from sectioned LNs. We evaluated 2 novel kits that use newly developed anti-CK-19 antibodies to diagnose LN metastases in breast cancer., Patients and Methods: We examined 159 LNs dissected that we sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. Diagnoses on the basis of the kits were compared with pathological diagnoses., Results: Of the 159 LNs, 68 were assessed as positive and 91 as negative in permanent section examination. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. Those of the high-power kit were 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, those for distinguishing macrometastases were 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 minutes, at a cost of less than $30 USD., Conclusion: The kits were accurate, fast, and cost-effective in diagnosing LN metastases without the loss of LN tissue., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Nonadherence to adjuvant endocrine therapy has been poorly studied in Asian patients with breast cancer. We therefore assessed adherence to endocrine therapy among women with breast cancer in Japan., Patients and Methods: We conducted a prospective observational study among Japanese women with hormone receptor-positive breast cancer. Patients brought their pill packets to visits for 1 year and answered a questionnaire. We also examined prescription records during the study period. Adherence to endocrine therapy was defined as patients who had taken > 80% of the pills according to the packets during the study. Clinicopathologic features and questionnaires were compared between adherent and nonadherent patients., Results: A total of 234 patients completed the trial, of whom 85% demonstrated adherence based on pill packets, and 98% demonstrated adherence based on prescription records. Mastectomy, higher stage, nodal metastasis and adjuvant chemotherapy were correlated with adherence based on pill packets. Adjuvant chemotherapy was an independent factor associated with adherence. According to the questionnaire, adherent patients were more likely to consult a nurse when they had trouble with their medication. These patients also emphasized the efficacy rather than the side effects of the medication. Nonadherent patients were aware that they were being nonadherent., Conclusion: The results of this study revealed that 85% of patients were adherent to endocrine therapy, but physicians were unaware of the nonadherent patients. Raised awareness of nonadherence and information sharing between patients and medical teams might increase adherence to endocrine therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Fine-needle aspiration cytology (FNAC) is a challenging and risky procedure for inexperienced clinicians to perform because of the proximity of the thyroid to the jugular veins, carotid arteries, and trachea. A phantom model for transfixion practice would help train clinicians in FNAC., Objective: To fabricate a tailored phantom with consideration for authenticity of size, touch, feel, and ultrasonographic (US) characteristics., Methods: A three-dimensional (3D) digital model of the human neck was reconstructed from computed tomography data of a subject. This model was used to create 3D-printed templates for various organs that require US visualization. The templates were injected with polymers that provided similar degrees of ultrasound permeability as the corresponding organs. For fabrication of each organ, the respective molds of organs, blood vessels, thyroid gland, and tumor were injected with the material. The fabricated components were then removed from the templates and colored. Individual components were then positioned in the neck mold, and agar gel was poured in. The complete phantom was then removed from the mold. Thereafter, 45 medical doctors and students performed ultrasound-guided FNAC using the phantom, following which they were queried regarding the value of the phantom., Results: The structure, US characteristics, and elasticity of the phantom were similar to those of the human subject. In the survey, all 45 participants replied that they found the phantom useful for FNAC training, and 30 medical students professed increased interest in thyroid diseases after using the phantom., Conclusions: We successfully fabricated a tailored thyroid gland phantom for transfixion practice. As most of the phantom parts are injected in molds fabricated using a 3D printer, they can be easily reproduced once the molds are fabricated. This phantom is expected to serve as an effective and fully tailored training model for practicing thyroid gland transfixion., (Copyright © 2017. Published by Elsevier Inc.)

Fatty acid binding protein 4 (FABP4), also known as adipocyte FABP or aP2, is secreted from adipocytes in association with lipolysis as a novel adipokine, and elevated serum FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the modulation of serum FABP4 level by therapeutic drugs. Sitagliptin (50 mg/day), a dipeptidyl peptidase 4 (DPP-4) inhibitor that increases glucagon-like peptide 1 (GLP-1), was administered to patients with type 2 diabetes (n = 24) for 12 weeks. Treatment with sitagliptin decreased serum FABP4 concentration by 19.7% (17.8 ± 1.8 vs. 14.3 ± 1.5 ng/ml, P < 0.001) and hemoglobin A1c without significant changes in adiposity or lipid variables. In 3T3-L1 adipocytes, sitagliptin or exendin-4, a GLP-1 receptor agonist, had no effect on short-term (2 h) secretion of FABP4. However, gene expression and long-term (24 h) secretion of FABP4 were significantly reduced by sitagliptin, which was not mimicked by exendin-4. Treatment with recombinant DPP-4 increased gene expression and long-term secretion of FABP4, and the effects were cancelled by sitagliptin. Furthermore, knockdown of DPP-4 in 3T3-L1 adipocytes decreased gene expression and long-term secretion of FABP4. In conclusion, sitagliptin decreases serum FABP4 level, at least in part, via reduction in the expression and consecutive secretion of FABP4 in adipocytes by direct inhibition of DPP-4., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

To evaluate bile acid (BA) metabolism in detail, we established a method for analyzing BA composition in various tissues and intestinal contents using ultra performance liquid chromatography/electrospray ionization mass spectrometry (UPLC/ESI-MS). Twenty-two individual BAs were determined simultaneously from extracts. We applied this method to define the differences in BA metabolism between two rat strains, WKAH and DA. The amount of total bile acids (TBAs) in the liver was significantly higher in WKAH than in DA rats. In contrast, TBA concentration in jejunal content, cecal content, colorectal content, and feces was higher in DA rats than in WKAH rats. Nearly all BAs in the liver were in the taurine- or glycine-conjugated form in DA rats, and the proportion of conjugated liver BAs was up to 75% in WKAH rats. Similar trends were observed for the conjugation rates in bile. The most abundant secondary BA in cecal content, colorectal content, and feces was hyodeoxycholic acid in WKAH rats and omega-muricholic acid in DA rats. Analyzing detailed BA profiles, including conjugation status, in a single run is possible using UPLC/ESI-MS. This method will be useful for investigating the roles of BA metabolism under physiological and pathological conditions.

The subject of our study was Awaji Island, an island located in the west of Japan that is surrounded by sea and that has serious problems relating to coastal debris. We conducted a long-term investigation focusing on three beaches and evaluated the results. The study was designed to develop an understanding of the actual situation, to inform local citizens, and raise their concerns about the problem of debris with a view to taking action against it. We obtained the following results: the amount, type, and ratio of debris changed according to weather and ocean conditions; debris also differs according to geographical conditions; social and economic activities of the surrounding area influence the type of debris encountered. Following this study, we have continued our investigation, and are continuing to gather data. At the same time, it is important to spread our ideas and enlighten people so as to encourage them not to dump debris. We hope that these actions manage to raise the level of consciousness among local citizens and to expand their anti-debris activities.

Despite the longstanding conclusion that behavior can reveal aspects of underlying anatomy and function, no generalized antenatal behavior screening has been developed to identify fetuses that may have central nervous system defects requiring further evaluation. We devised a brief ultrasound examination to distinguish fetuses with compromised central nervous system function from the general population and evaluated it with this study. The study design compared behavioral findings obtained by retrospectively reviewing the ultrasound examinations of 5 fetuses that had abnormal behavior with prospectively obtained findings of 29 normal fetuses. Median time for brief examination criteria was 50 min (range, 30-60 min). The only case undetectable by this brief ultrasound examination has an eye-movement period significantly longer than the normal upper limit. Using this method as a screening test may make it possible to include assessment of fetal brain function as part of routine antenatal care.

Background: Activated monocytes/macrophages, neutrophils, endothelial cells and smooth muscle cells participate in the restenosis processes. Monocytes/macrophages and neutrophils are activated by lipopolysaccharide (LPS) via CD14. Endothelial cells and smooth muscle cells are also stimulated by soluble CD14 (sCD14)-LPS complexes., Methods: We tested the hypothesis that C(-260)-->T polymorphism of the CD14 gene and sCD14 might be predictors for in-stent restenosis. We analyzed 129 consecutive patients who underwent elective coronary stenting. The restenosis was defined as > or =50% diameter stenosis at follow-up angiography., Results: The prevalence of the T/T genotype and the concentration of sCD14 were significantly higher in the restenosis group than in the no-restenosis group. This CD14 polymorphism also affected the levels of sCD14, therefore, we divided the patients into four groups. The loss index was 24.8% in C/C or C/T and < or =50th percentile of sCD14, 35.9% in T/T and < or =50th percentile of sCD14, 44.2% in C/C or C/T and >50th percentile of sCD14, and 49.1% in T/T and >50th percentile of sCD14 (P=0.02). The restenosis rate was 10.0%, 26.7%, 26.2% and 50.0% in each group, respectively (P=0.003). In the multivariate analysis, T/T and >50th percentile of sCD14 was the independent predictor for in-stent restenosis., Conclusions: This study showed that the T/T genotype with a high level of sCD14 is an independent predictor of in-stent restenosis. The activation of monocytes/macrophages, endothelial cells and smooth muscle cells mediated by CD14 and/or sCD14 may play an important role in the restenosis processes.