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Inhalation therapy can effectively treat chronic obstructive pulmonary disease (COPD), but the physical factors determining the appropriate aerosol delivery into the targeted airways remain unclear. The problem is nontrivial because pulmonary structures differ among individual patients with COPD and depend on the severity of the disease. In an in silico evaluation, the present study investigates the differences in particle transport and deposition in the airways of three patients with different degrees of COPD. Specific pulmonary airway models were reconstructed based on the computed tomography data of three patients with a different degree of COPD severity. The transport and deposition of inhaled particles in the airways were evaluated in a computational fluid dynamics simulation and a Lagrangian multiphase model. The sizes of the inhaled particles (1.0, 2.5, 5.5, 8.5, and 10.0 μm) were representative of drug particles delivered from inhalation devices, including dry powder inhalers (DPIs). The deposition behaviors of the inhaled particles strongly depended on the individual geometrical structure of the airways. The largest inhaled particles (10.0 μm) were most strongly affected by inertia and were deposited mostly in the oropharynx; consequently, they were rare in the bronchi. In contrast, the smallest inhaled particles (1.0 μm) were effectively delivered distally with the airflow. The spatial distributions and amounts of deposited particles in the airways obviously differed among the three COPD patients. Small particles are preferred as they can penetrate the inner lung regions. The results can assist the design and development of powder formulations and DPIs for patients with various severities of COPD.

Purpose:Coronavirus disease (COVID-19) has been declared a pandemic and the number of infected individuals and deaths continue to increase globally. COVID-19 is transmitted through airborne droplets formed during coughing and sneezing and from the saliva of infected patients. Medical healthcare workers are often at risk of infection. This study measured the aerosol derived from the droplets of patients during the conversation.Methods:Overall, 25 patients aged 21 to 87 years were enrolled. The amount of droplets from the patient was measured under the following four conditions: 1) no conversation with the mask on; 2) conversation with the mask on; 3) conversation without the mask; and 4) no conversation without the mask. Particulate matter (PM) with an aerodynamic diameter of 2.5 μm or less (PM2.5) and PM with a diameter of 10 μm or less (PM10) were measured as representative aerosols at a position of 1 meter from the patients.Results:The concentrations of PM2.5 (µg/m3) were as follows: 22.7 ± 10.2 before the conversation with the mask, 24.2 ± 10.2 during the conversation with the mask, 32.3 ± 14.7 during the conversation without the mask, and 23.1 ± 9.9 after the conversation without the mask. The concentrations of PM10 (µg/m3) were as follows: 39.8 ± 18.2 before conversation with the mask, 41.9 ± 18.5 during conversation with the mask, 55.5 ± 27.2 during conversation without the mask, and 40.4 ± 17.8 after conversation without the mask. The variations in the PM2.5 and PM10 correlated negatively with the age of patients (PM2.5: r = -0.51, p = 0.0009 and PM10: r = -0.53, p = 0.0063).Conclusion:Wearing a mask can prevent airborne droplet formation and reduce transmission of infection.

Evidence showing the functional significance of the choroid plexus is accumulating. Although it is clinically well-known that calcification is frequently seen in the choroid plexus of aged human brains, it is unclear why calcification occurs in the aged choroid plexus and what exert effects on the calcification has. In this study, immunohistochemical localizations of collagens and other molecules related to fibrosis or calcification were investigated on the choroid plexus of autopsied human brains. Densely fibrous or calcified materials were located in the stroma just below the epithelial cells of the choroid plexus of all human brains examined. Immunoreactivity for collagen type I was identified in the stroma just below the epithelial cells, consistent with the densely fibrous or calcified area, whereas that for collagen type III was observed in almost all stroma other than the densely fibrous or calcified areas. Linear or membranous immunoreactivity for collagen type IV was intermittently localized on the epithelium-facing side of the materials, suggesting an injured basement membrane. In addition, clear immunoreactivity for osteopontin was localized on the epithelium-facing side of the fibrous or calcified materials as well as in the cytoplasm of epithelial cells. These findings indicate that collagen type I exists in contact with osteopontin in and around the densely fibrous or calcified materials in the choroid plexus. They suggest that the densely fibrous or calcified materials are deposited in the subepithelial stroma just below an injured basement membrane of epithelial cells via the collagen type I and osteopontin.

Background Childhood rhabdomyosarcoma (RMS) of perineal or perianal origin (PRMS) is rare, accounting for only 2% of all RMSs. PRMS has been reported to show different characteristics depending on the patient’s age, and patients aged 10 years or older have a poor prognosis. Disseminated intravascular coagulation (DIC) is considered to be an uncommon complication of RMS. However, it could occur occasionally in patients with widespread RMS with bone marrow infiltration. Pulmonary lymphangitic sarcomatosis (PLS) has been reported to be rare, and to our knowledge, only 18 cases (including 4 patients with RMS) have been reported to date. Case report A 15-year-old female patient with suspected RMS was admitted to our hospital. The patient was diagnosed with PRMS following radiological evaluations and effusion cytology, and chemotherapy was initiated on the 6th day of admission. During the course, the patient suffered from severe dyspnea and DIC. Despite treatment, the bleeding tendency did not improve, and hepatic and renal failure progressed. The patient died of progressive respiratory failure on the 13th day of admission. An autopsy, performed 2 h after death, revealed a perianal tumor with pseudoalveolar growth pattern. In the lungs, a relatively large number of small metastatic foci, presumed to be lymphatic spread, were identified. It was diagnosed as PLS due to alveolar RMS. Conclusion Although PLS is reported to be an unexpected form of metastasis, it might cause severe dyspnea in patients with RMS, as 4 of 18 reported cases of PLS are associated with RMS.

To date, almost all case reports of insulin‐derived amyloidosis described the presence of a subcutaneous mass that was observable on physical examination. This report presents two cases of insulin‐derived amyloidosis without palpable masses at insulin injection sites. In both cases, blood glucose concentrations improved, and the insulin dose could be reduced by an average of 45% after changing the insulin injection sites. The insulin absorption at the site was reduced to at most 40% of that at a normal site in one case. Magnetic resonance imaging and ultrasonography were useful to screen and differentiate insulin‐derived amyloidosis without a palpable mass. This report showed that insulin‐derived amyloidosis without a palpable mass can be present at the insulin injection site, and has similar clinical effects to insulin‐derived amyloidosis with palpable masses., This report showed that insulin‐derived amyloidosis without a palpable mass can be present at the insulin injection site and has similar clinical effects to insulin‐derived amyloidosis with palpable masses. Magnetic resonance imaging and ultrasonography were useful to screen and differentiate insulin‐derived amyloidosis without a palpable mass.

This paper studies a static hedging problem of derivatives when the model risk exists. When the payoff of derivative depends on one asset, Matsumoto (Int J Financ Eng 4(4):1750042, 2017b) solves the problem. We extend his result to derivatives on two assets. Though the optimal solution is more complicated, we show that the problem can be solved numerically in an algebraic way. Further we give some simple numerical examples to show our method works well.

We studied the magnetocaloric effect in a single crystal GdTiO3. Single crystal GdTiO3 had a second order phase transition from a paramagnetic to ferrimagnetic state at 33 K. The maximum entropy change of - Δ S = 0.10 J/cm3 K was observed in a 5 T field at the transition temperature. A small anisotropy was found in the magnetization and specific heat in low magnetic fields. The magnetization showed no hysteresis. Temperature dependencies of entropy, which are important for analyzing the refrigeration cycle, were calculated from the magnetization and specific heat measurements. These results indicate that GdTiO3 has the potential for applications as a magnetic refrigerant for hydrogen liquefaction.

The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.

Glucose metabolism produces lactate and hydrogen ions in an anaerobic environment. Cerebral ischemia or hypoxia is believed to become progressively lactacidemic. Monocarboxylate transporters (MCTs) in endothelial cells are essential for the transport of lactate from the blood into the brain. In addition, it is considered that MCTs located in astrocytic and neuronal cells play a key role in the shuttling of energy metabolites between neurons and astrocytes. However, roles of lactate in the brain remain to be clarified. In this study, the localization of lactate transporters and a receptor for cellular uptake of lactate was immunohistochemically examined in autopsied human brains. Immunoreactivity for MCT1 was observed in the apical cytoplasmic membrane of some epithelial cells in the choroid plexus as well as astrocytes and the capillary wall, whereas that for MCT4 was found in the basolateral cytoplasmic membrane of small number of epithelial cells as well as astrocytes and the capillary wall. In addition, immunoreactivity for the hydroxy-carboxylic acid 1 receptor (HCA1 receptor), a receptor for cellular uptake of lactate, was also found on the basolateral cytoplasmic membrane of epithelial cells as well as astrocytic and neuronal cells. Immunoreactivity for lactate dehydrogenase (LDH)-B was observed in the cytoplasm of epithelial cells in the choroid plexus as well as astrocytes and the capillary wall. These immunohistochemical findings indicate the localization of MCT1, MCT4, the HCA1 receptor, and LDH-B in epithelial cells of the choroid plexus as well as astrocytes, and suggest the transport of intravascular lactate into the brain through epithelial cells of the choroid plexus as well as cerebral vessels and the possibility of lactate being utilized in epithelial cells.

A simple method for quantitative prediction of V th shift due to plasma process induced charging damage considering protection device effect is proposed. Based on this prediction, the gate oxide of transistor may be stressed by high voltage during plasma process even with efficient protection device such as gated diode, and then enormous V th shift can be occurred. In this paper, we propose a new protection device which works at extremely lower voltage with higher current.

To investigate the correlation between mineral formation and enhanced expressions of some proteins using undecalcified frozen bone sections. Histological studies have revealed that some proteins, such as BMP2, BMPR1A, and Connexin 43, are expressed in and around sites of ectopic ossification. However, the relationship between the expressed proteins considered to be associated with the ossification and mineral formation in vivo is not clear. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1)-mutant spinal hyperostotic TWY mice and ICR mice as controls were euthanized after calcein labeling, and undecalcified frozen sections were obtained from the middle thoracic spine. Intervertebral disc areas were examined histologically and by measuring calcein-labeled areas and areas showing immunoreactivity for BMP2, BMPR1A, and Connexin 43. Calcein-labeled areas, indicating mineralization in the ectopic mineralization sites, were significantly larger in the mutant mice than in controls. The expression of Connexin 43 was elevated in the annulus fibrosus. Increases in the calcein-labeled areas was not correlated with increases in the areas showing immunoreactivity for Connexin 43 in the annulus fibrosus. There was no statistical correlation between enhanced immunohistochemical expression and elevated calcein-labeled areas. By applying the morphometrical analysis method using undecalcified frozen sections to ENPP1-mutant mice, quantitative evaluation of the mineralization and proteins expressed in the surrounding area in the same animal became possible.

A magnetic refrigerator that makes use of the magneto-caloric effect realizes a highly efficient cooling device. Since the cooling power of magnetic refrigerators depends largely on the strength of the magnetic field, the use of a superconducting magnet is essential. Using magnetic refrigeration, achieving a liquefaction efficiency of larger than 50% is theoretically possible, which is twice that of conventional gas expansion refrigerators. In this study, an active magnetic regenerative refrigerator, one of the magnetic refrigerators using a superconducting solenoid, was built and hydrogen liquefaction was successfully demonstrated.

Background We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS). Methods Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (C max) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR. Results At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan–Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 μg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration. Conclusion Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine C max, and more than 1.1 µg/mL of C max is necessary for CR.

It has been suggested that urate plays a protective role in neurons, while hyperuricemia is correlated with atherosclerosis and cardiovascular disease. However, whether there is a system that directly transports urate into the brain remains to be clarified. In this study, the localization of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), which are known to be representative reabsorptive urate transporters, was immunohistochemically examined in autopsied human brains. Immunoreactivity of GLUT9 was observed on the apical side of the cytoplasm of epithelial cells in the choroid plexus and in the cilia of ependymal cells of the human brain. Immunoreactivity of URAT1 was observed on the basolateral side of the cytoplasm of epithelial cells in the choroid plexus. In addition, immunoreactivity of GLUT9 and URAT1 was not observed in microvessels of the human brains. The choroid plexus and renal proximal tubule were similar in having a polarized distribution of these two transporters with the two transporters on opposite membranes, but the two transporters' distribution differs between the choroid plexus and the kidney in terms of which membrane (apical/basal) expresses which transporter. These findings support the hypothesis of the direct transport of intravascular urate into the central nervous system through the choroid plexus.

This paper studies a hedging problem in the market where an investor can observe a risky asset price process but he does not know true parameters of this process. The investor is assumed to hedge derivatives on the risky asset by a partial super-hedging strategy in order to cut the hedging cost. We show two partial differential equations which play an important role to solve the optimal hedging cost and an optimal strategy. Further we analyze the optimal hedging cost numerically by trinomial models.

The Fc receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney. The treatment suppressed the phosphorylation of 3BP2 in white blood cells from the spleen and significantly inhibited the phosphorylation of p38MAPK in the kidney but did not affect expression of neonatal Fc receptor. These findings indicate the important roles and mechanisms of Fcγ receptors I and III in the development of autoimmune glomerulonephritis and suggest the possible application of Syk inhibitors as novel medicines for the glomerulonephritis.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to β-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with β-lactamase inhibitor showed low MIC90 values.

IntroductionPhysical activity is one of the major modifiable factors for promotion of public health. Although it has been reported that financial incentives would be effective for promoting health behaviours such as smoking cessation or attendance for cancer screening, few randomised controlled trials (RCTs) have examined the effect of financial incentives for increasing the number of daily steps among individuals in a community setting. The aim of this study is to investigate the effects of financial incentives for increasing the number of daily steps among community-dwelling adults in Japan.Methods and analysisThis study will be a two-arm, parallel-group RCT. We will recruit community-dwelling adults who are physically inactive in a suburban area (Nakayama) of Sendai city, Japan, using leaflets and posters. Participants that meet the inclusion criteria will be randomly allocated to an intervention group or a waitlist control group. The intervention group will be offered a financial incentive (a chance to get shopping points) if participants increase their daily steps from their baseline. The primary outcome will be the average increase in the number of daily steps (at 4–6 weeks and 7–9 weeks) relative to the average number of daily steps at the baseline (1–3 weeks). For the sample size calculation, we assumed that the difference of primary outcome would be 1302 steps.Ethics and disseminationThis study has been ethically approved by the research ethics committee of Tohoku University Graduate School of Medicine, Japan (No. 2018-1-171). The results will be submitted and published in a peer-reviewed scientific journal.Trial registration numberUMIN000033276; Pre-results.

Purpose. Trichotillomania is a behavioral and mental disorder and is characterized by a recurring habit of pulling out one’s hair. The differential diagnosis between trichotillomania and other hair loss conditions such as alopecia areata is difficult for ophthalmologists. We report a rare case of bilateral trichotillomania of the eyelashes that was triggered by anxiety about nocturnal enuresis. Case Report. A healthy 9-year-old Japanese boy presented with a bilateral loss of his eyelashes. His parents had believed that his loss of eyelashes was due to alopecia, an autoimmune disorder that results in hair loss, of the eyelashes. Our initial examination revealed that he had suffered from nightly nocturnal enuresis from childhood and was scheduled to go on a school trip the following month. He feared that his school mates might find out about his enuresis, and he said that the anxiety was the cause of the eyelash trichotillomania. The trichotillomania was resolved by discussion among the student, his family, teacher, and school counselor. Conclusion. To the best of our knowledge, this is the first report of eyelash trichotillomania caused by anxiety about nocturnal enuresis. Ophthalmologists should be aware that a patient without eyelashes may not be due to alopecia but some anxiety-producing events. In addition, discussion of the anxiety-producing factor among the parents, teacher, and school counselors can resolve the trichotillomania.