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Neuropsin ( KLK8), a serine protease of the kallikrein family, is thought to be involved in the function of keratinocytes, i.e. migration, differentiation and desquamation. However, how neuropsin participates is still unknown. To observe the epidermal function of serine protease in neuropsin-deficient mice. We irradiated the skin of neuropsin-deficient mice with ultraviolet light to induce acute inflammation and compared the morphology with that of wild-type mice. We observed a phenotypic change in the epidermis. An acute inflammatory dose of ultraviolet light induced a marked increase in neuropsin mRNA expression in the skin. The signal intensity of the mRNA expression was highest on day 2–3 after irradiation, when keratinocytes were aligned irregularly in the recovery period. Morphological comparison between neuropsin –/– and +/+ mice revealed that an irregular alignment of cells in the thickened epidermis was obvious on day 2 after irradiation in the wild-type mice, whereas it was prolonged for at least 2 days in the neuropsin-deficient mice. The stratum corneum of neuropsin-deficient mice was remarkably thicker than that of the wild-type mice at 5, 14 and 21 days after irradiation. The increase, as a response to this stimulus, in involucrin immunoreactivity, a marker for cell envelope assembly, was delayed in the mutant mice. Thus, neuropsin might be involved early in the process of differentiation, such as in the assembly of the cell envelope, but not in migration and desquamation. [ABSTRACT FROM AUTHOR]

Prcis: The study suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner., Aims: To evaluate differences in systemic brain-derived neurotrophic factor (BDNF) levels between primary open angle glaucoma (POAG) patients and normal tension glaucoma (NTG) patients., Methods: This study collected blood samples from 260 NTG patients, 220 age-matched POAG patients, and 120 age-matched cataract patients (as controls). BDNF levels were measured with an antibody-conjugated bead assay system (Luminex)., Results: We found that plasma BDNF levels in the NTG group were significantly lower than in the POAG and cataract control groups. There was no significant difference between the POAG and cataract groups., Conclusion: This result suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Currently, task-oriented dialogue systems that perform specific tasks based on dialogue are widely used. Moreover, research and development of non-task-oriented dialogue systems are also actively conducted. One of the problems with these systems is that it is difficult to switch topics naturally. In this study, we focus on interview dialogue systems. In an interview dialogue, the dialogue system can take the initiative as an interviewer. The main task of an interview dialogue system is to obtain information about the interviewee via dialogue and to assist this individual in understanding his or her personality and strengths. In order to accomplish this task, the system needs to be flexible and appropriate for detecting topic switching and topic breaks. Given that topic switching tends to be more ambiguous in interview dialogues than in task-oriented dialogues, existing topic modeling methods that determine topic breaks based only on relationships and similarities between words are likely to fail. In this study, we propose a method for detecting topic breaks in dialogue to achieve flexible topic switching in interview dialogue systems. The proposed method is based on multi-task learning neural network that uses embedded representations of sentences to understand the context of the text and utilizes the intention of an utterance as a feature. In multi-task learning, not only topic breaks but also the intention associated with the utterance and the speaker are targets of prediction. The results of our evaluation experiments show that using utterance intentions as features improves the accuracy of topic separation estimation compared to the baseline model.

Background: Little is known about the kinetics and clinical significance of saliva human herpesvirus-6 (HHV-6) DNA after hematopoietic stem cell transplantation (HSCT)., Methods: In this observational study, we quantified HHV-6 DNA in serially collected plasma and saliva from allogeneic HSCT recipients. Associations between the status of salivary HHV-6 DNA and the development of HHV-6 encephalitis, depression, and oral mucosal graft-versus-host disease (GVHD) were retrospectively analyzed., Results: A total of 787 plasma and 434 saliva samples were collected from 56 patients. The cumulative incidence of HHV-6 DNA in plasma and saliva at 60 days after transplantation was 51.8% and 83.9%, respectively. The peak level of salivary HHV-6 DNA was significantly higher in patients who displayed plasma HHV-6 DNA than in those who did not (median, 51,584 copies/mL vs 587 copies/mL; P < .0001). Salivary HHV-6 DNA levels increased after positive plasma HHV-6 DNA was detected and remained high during observation period. Despite the frequent occurrence of positive salivary HHV-6 DNA, no patient developed depression. Positivity of salivary HHV-6 DNA was not significantly associated with the development of HHV-6 encephalitis (P = 1.00, Fisher's exact test) or oral mucosal GVHD (P = .71, Grey's test). No significant relationship between salivary HHV-6 DNA and these diseases was found even when comparing higher HHV-6 DNA loads in saliva., Conclusion: Salivary HHV-6 DNA levels increased after HHV-6 DNA was detected in the blood. However, no epidemiological evidence was shown to support a role of salivary HHV-6 in the development of HHV-6 encephalitis, depression, and oral mucosal GVHD., (© 2020 Wiley Periodicals LLC.)

Purpose: To investigate the intraocular pressure (IOP)-lowering effects of omidenepag isopropyl (OMDI), a potent and highly selective prostanoid EP2 receptor agonist, as a potential first-line ocular hypotensive agent when combined with existing antiglaucoma agents in conscious ocular normotensive monkeys. Methods: Male cynomolgus monkeys were examined under conscious conditions. OMDI ophthalmic solution alone was topically applied to an eye or combined with other ophthalmic solutions at 5-min intervals. The contralateral eye was left untreated. IOP was measured before and at 2, 4, 6, and 8 h after instillation. Results: Topical application of OMDI to the eye resulted in statistically significant IOP reduction, which lasted for at least 6 h. The IOP-lowering effects of OMDI concomitantly administered with any of the tested antiglaucoma agents (timolol, brinzolamide, netarsudil, ripasudil, and brimonidine) were greater than those of OMDI alone. Furthermore, these enhanced IOP responses to their concomitant use were statistically significant compared with those of the tested antiglaucoma agents alone. Any combination of OMDI with the tested agents did not lead to serious abnormalities either systemically or locally in the eye. Conclusions: We demonstrated that OMDI has additive IOP-lowering effects when administered in combination with various antiglaucoma agents, namely, β-adrenergic antagonist, carbonic anhydrase inhibitor, Rho-associated coiled-coil containing protein kinase inhibitors, and α2-adrenergic agonist. These results suggest that OMDI provides additional clinical benefits because of its unique mechanisms of action when combination therapy is required.

We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of azacitidine, a partial cytogenetic response was confirmed. Azacitidine maintenance therapy successfully maintained a low level of recipient-origin peripheral blood cells with a stable hematological condition. Azacitidine may therefore be a promising therapeutic option for PMF patients who relapse after allogeneic stem cell transplantation.

A 51-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia underwent a second cord blood transplantation followed by maintenance therapy with interferon-α. After 33 months, she developed cardiogenic shock caused by advanced atrioventricular block. Laboratory tests revealed increased myocardium enzymes, and ultrasonic cardiography demonstrated mild thickening of the left ventricular wall. She was diagnosed with myocarditis and successfully treated using prednisolone. Myocarditis after allogeneic stem cell transplantation is a rare but potentially fatal complication. However, it is important for physicians to be aware of this complication because all of the symptoms may be reversed with immunosuppressive treatment.

Cerebral tracts connect separated regions within a brain and serve as fundamental structures that support integrative brain functions. However, understanding the mechanisms of cerebral tract development, macro-circuit formation, and related disorders has been hampered by the lack of an in vitro model. Here, we developed a human stem cell-derived model of cerebral tracts, which is composed of two spheroids of cortical neurons and a robust fascicle of axons linking these spheroids reciprocally. In a microdevice, two spheroids of cerebral neurons extended axons into a microchannel between the spheroids and spontaneously formed an axon fascicle, mimicking a cerebral tract. We found that the formation of axon fascicle was significantly promoted when two spheroids extended axons toward each other compared with axons extended from only one spheroid. The two spheroids were able to communicate electrically through the axon fascicle. This model tissue could facilitate studies of cerebral tract development and diseases., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)