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In this study, we evaluated the drug release behavior of diameter customized TiO2 nanotube layers fabricated by anodization with various applied voltage sequences: conventional constant applied potentials of 20 V (45 nm) and 60 V (80 nm), a 20/60 V stepped potential (50 nm [two‐diameter]), and a 20–60 V swept potential (49 nm [full‐tapered]) (values in parentheses indicate the inner tube diameter at the top part of nanotube layers). The structures of the 50 nm (two‐diameter) and 49 nm (full‐tapered) samples had smaller inner diameters at the top part of nanotube layers than that of the 80 nm sample, while the outer diameters at the bottom part of nanotube layers were almost the same size as the 80 nm sample. The 80 nm sample, which had the largest nanotube diameter and length, exhibited the greatest burst release, followed by the 50 nm (two‐diameter), 49 nm (full‐tapered), and 45 nm samples. The initial burst released drug amounts and release rates from the 50 nm (two‐diameter) and 49 nm (full‐tapered) samples were significantly suppressed by the smaller tube top. On the other hand, the largest proportion of the slow released drug amount to the total released drug amount was observed for the 50 nm (two‐diameter) sample. Thus, 50 nm (two‐diameter) achieved suppressed initial burst release and large storage capacity. Therefore, this study has, for the first time, applied TiO2 nanotube layers with modulated diameters (two‐diameter and full‐tapered) to the realization of a localized drug delivery system (LDDS) with customized drug release properties. [ABSTRACT FROM AUTHOR]

The corrosion behavior of carbon steel covered with coating films containing Al2(SO4)3, CaO, and BaO was examined under a sulfuric acid mist environment containing chloride. CaSO4･2H2O and BaSO4 were formed as the corrosion products in the coating film and prevented the penetration of corrosives, in particular BaSO4 was highly effective. Furthermore, the rust layer containing CaCO3 adhered to the carbon steel substrate suppressed the penetration of chloride. The formation of these corrosion products suppressed the anodic reaction, resulting in higher corrosion resistance of the carbon steel in the chloride‐containing acid environment. [ABSTRACT FROM AUTHOR]

Objective: The formation of 24S‐hydroxycholesterol is a brain‐specific mechanism of cholesterol catabolism catalyzed by cholesterol 24‐hydroxylase (CYP46A1, also known as CH24H). CH24H has been implicated in various biological mechanisms, whereas pharmacological lowering of 24S‐hydroxycholesterol has not been fully studied. Soticlestat is a novel small‐molecule inhibitor of CH24H. Its therapeutic potential was previously identified in a mouse model with an epileptic phenotype. In the present study, the anticonvulsive property of soticlestat was characterized in rodent models of epilepsy that have long been used to identify antiseizure medications. Methods: The anticonvulsive property of soticlestat was investigated in maximal electroshock seizures (MES), pentylenetetrazol (PTZ) acute seizures, 6‐Hz psychomotor seizures, audiogenic seizures, amygdala kindling, PTZ kindling, and corneal kindling models. Soticlestat was characterized in a PTZ kindling model under steady‐state pharmacokinetics to relate its anticonvulsive effects to pharmacodynamics. Results: Among models of acutely evoked seizures, whereas anticonvulsive effects of soticlestat were identified in Frings mice, a genetic model of audiogenic seizures, it was found ineffective in MES, acute PTZ seizures, and 6‐Hz seizures. The protective effects of soticlestat against audiogenic seizures increased with repetitive dosing. Soticlestat was also tested in models of progressive seizure severity. Soticlestat treatment delayed kindling acquisition, whereas fully kindled animals were not protected. Importantly, soticlestat suppressed the progression of seizure severity in correlation with 24S‐hydroxycholesterol lowering in the brain, suggesting that 24S‐hydroxycholesterol can be aggressively reduced to produce more potent effects on seizure development in kindling acquisition. Significance: The data collectively suggest that soticlestat can ameliorate seizure symptoms through a mechanism distinct from conventional antiseizure medications. With its novel mechanism of action, soticlestat could constitute a novel class of antiseizure medications for treatment of intractable epilepsy disorders such as developmental and epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of major depressive disorder (MDD) in adolescent and young adult (AYA) patients with cancer in Japan and identify risk factors for MDD among these patients. Methods: This was a matched cohort study using a large claims database in Japan. Included patients were aged 15–39 years, newly diagnosed with cancer during 2012–2017 and assessable for a follow‐up period of 12 months. Kaplan–Meier estimates and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for MDD in the AYA patients with cancer versus age‐, sex‐ and working status‐matched cancer‐free controls. A subgroups analysis of the AYA patients with cancer was performed to explore MDD risk factors. Results: A total of 3559 AYA patients with cancer and 35,590 matched controls were included in the analysis. Adolescent and young adult patients with cancer had a three‐fold higher risk for MDD compared with cancer‐free controls (HR, 3.12; 95% CI, 2.64–3.70). Among cancer categories with >100 patients, patients with multiple cancer categories, including those with metastatic cancer (HR, 6.73, 95% CI, 3.65–12.40) and leukemia (HR, 6.30; 95% CI, 3.75–10.58), had the greatest MDD risk versus matched controls. Patients who received inpatient chemotherapy as initial treatment had a higher risk for MDD than patients without chemotherapy (HR, 0.43; 95% CI, 0.30–0.62). Conclusions: Adolescent and young adult patients in Japan with cancer are at high risk for MDD. Particularly, those with multiple cancer categories, leukemia, and those who receive aggressive anticancer treatments should be monitored closely for symptoms of MDD. [ABSTRACT FROM AUTHOR]

The corrosion behavior of carbon steel coated with a zinc‐rich paint containing two metallic compounds, Al2(SO4)3 and CaO, as anticorrosive additives was examined under wet and dry cyclic corrosion test conditions. The zinc‐rich paint coating without the two metallic compounds formed a white corrosion product and red iron rust on the surface after the corrosion test, whereas the coating with the metallic compounds showed reduced surface corrosion products. The corrosion current density of the painted steel substrate decreased drastically due to the incorporation of metallic compounds in the paint. The zinc‐rich paint coating modified with the metallic compounds contained dispersed simonkolleite (Zn5(OH)8Cl2·H2O) phase and possibly very fine CaSO4 particles, which remarkably improved the protectiveness of the zinc‐rich paint coating. [ABSTRACT FROM AUTHOR]

Stress corrosion cracking (SCC) of pure copper in bentonite clay was examined using a slow strain rate test (SSRT). Bentonite was swollen with pure water or aqueous solutions containing NH3 of 5 and 10 mM. Thick corrosion films and particulate deposits were formed on the copper surface after the SSRT. Typical tarnish rupture‐type SCC occurred on pure copper in swollen bentonite with and without NH3. The crack propagation rate was enhanced by NH3. It is confirmed that a thick oxide layer was formed on copper during plastic deformation, resulting in tarnish crack‐type SCC. Many particulate deposits observed on the surface were formed due to the rapid dissolution of Cu2+ ions to form porous CuO at local deformed sites, regardless of the SCC occurrence. [ABSTRACT FROM AUTHOR]

Objective: Patients with cancer are at high risk of depression. However, the risk of major depressive disorder (MDD) after cancer diagnosis has not been studied in a population setting in Japan. This cohort study used a Japanese medical claims database to examine time to MDD in cancer patients and the risk of MDD (hazard ratio; HR) compared with matched cancer‐free controls. Methods: Primary endpoint was time to MDD (starting 6 months before cancer diagnosis) in adult (18–74 years) cancer patients; secondary endpoint was time to MDD (6 months before to 12 months after cancer diagnosis) in a matched cohort of cancer patients and cancer‐free controls. Multivariate analyses were performed to determine HRs for all cancers and for each cancer site. Results: Of 35 008 cancer patients (mean age, 53.3 years), 2201 (6.3%) were diagnosed with MDD within 66 months. Matched cancer patients (n = 30 372) had an elevated risk of MDD compared with cancer‐free controls (n = 303 720; HR [95% confidence interval] 2.96 [2.77–3.16]). MDD risk was highest in patients with multiple cancers, pancreatic cancer, and brain cancer. Compared with middle‐aged patients, risk was higher in patients <40 years old and lower in patients ≥65 years old; risk tended to be higher in women than in men. Conclusions: Compared with cancer‐free individuals, Japanese patients with cancer, mostly <65 years old, had an almost threefold higher risk of developing MDD within 12 months of cancer diagnosis. Physicians should watch for MDD in cancer patients and treat when necessary. [ABSTRACT FROM AUTHOR]

Keywords: administrative claims, healthcare; cancer; depressive disorder, major; epidemiology; oncology; spouses EN administrative claims, healthcare cancer depressive disorder, major epidemiology oncology spouses 1224 1227 4 07/04/20 20200701 NES 200701 Key Points Using a Japanese medical insurance database, we determined the risk of major depressive disorder (MDD) in spouses of newly diagnosed cancer patients compared with patients and with spouses of cancer-free individuals. We measured the time to MDD diagnosis from 6 months before to 12 months after the index month in cancer patients with spouses, in the spouses of those cancer patients, in cancer-free individuals with spouses, and in the spouses of those cancer-free individuals. DISCUSSION In this Japanese database analysis, spouses of cancer patients were at elevated risk of MDD diagnosis compared with spouses of cancer-free individuals, but at approximately half the risk of cancer patients. [Extracted from the article]

Cancer risk associated with radiation exposure is considered the result of concurrent exposure to other natural and manmade carcinogens. Available data on the molecular characteristics of cancer after simultaneous exposure to radiation and chemicals are insufficient. In our study, we used a mouse thymic lymphoma (TL) model that was synergistically induced by simultaneous exposure to X-rays and N-ethyl- N-nitrosourea (ENU) at subcarcinogenic doses and analyzed the mutation frequency and spectrum of the TL-associated genes Ikaros, Notch1, p53 and Kras. We found that the point mutation frequency in Ikaros was significantly increased to 47% for simultaneous exposure compared to 13 and 0% for X-ray and ENU exposure alone, respectively. These mutations were mostly G:C > A:T at non-CpG sites and T:A > C:G, both of which are characteristic of ENU mutagenesis. About half of the point mutations were accompanied by loss of heterozygosity (LOH), typical of X-irradiation. The remaining half did not include LOH, which suggests that they were dominant-negative mutations. In Notch1, the frequency of abnormalities was high (>58%) regardless of the treatment, suggesting that Notch1 aberration may be important for T-cell lymphomagenesis. The p53 and Kras mutation frequencies were low for all treatments (<23%). Importantly, the frequency of TLs containing mutations in multiple genes, especially both Ikaros and Notch1, increased after simultaneous exposure. Thus, after simultaneous exposure, Ikaros is a critical target and is inactivated by ENU-induced point mutations and/or X-ray-induced LOH in T-cell lymphomagenesis. Furthermore, concomitant alterations of multiple tumor-associated genes may contribute to enhanced lymphomagenesis after simultaneous exposure. [ABSTRACT FROM AUTHOR]

Background: The sudden appearance of hypotension and oliguria without obvious cause following stable circulation and respiration in preterm infants is frequent in Japan. Such episodes are referred to as late-onset circulatory dysfunction of premature infants (LCD). Volume expanders and inotropic agents are often ineffective against this condition, whereas i.v. steroids are significantly effective. A major problem is that cystic periventricular leukomalacia (PVL) often develops a few weeks after an episode. The aim of the present study was to clarify the risk factors, including LCD, related to cystic PVL. Methods: A case–control study was performed for preterm infants who were delivered at <33 weeks of gestation and admitted to seven neonatal intensive care units in Japan. Cystic PVL infants were stratified into early-onset PVL diagnosed within 28 days of age and late-onset PVL diagnosed after more than 28 days of age. The reported and new risk factors for PVL, for each group of PVL infants, and for all PVL infants, were compared with controls. Results: Thirty-two infants were diagnosed with cystic PVL (17 early-onset and 15 late-onset). All PVL infants significantly differed from controls on Apgar score, number of abortions and pregnancies, intraventricular hemorrhage, and LCD. LCD was diagnosed in 28.1% of both PVL groups compared with 6.3% of controls ( P = 0.02). Multivariate analysis demonstrated significant association between late-onset PVL and LCD. Conclusion: LCD was significantly associated with cystic PVL, especially late-onset PVL. Elucidating the cause of LCD might reduce the incidence of PVL and improve the neurological prognosis of preterm infants. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the cerebral blood flow of the posterior cerebral arteries (PCAs) in neonates in relation to the onset of periventricular leukomalacia (PVL). Methods: Among 57 low-birth-weight neonates studied, 7 were diagnosed with PVL with cyst formation on sonography and MRI. The mean cerebral blood flow velocity (CBFV) was measured in all the neonates by Doppler sonography through the posterior fontanel separately in the right and left PCA at days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, 56, and 70 following birth. Results: In the 7 neonates with PVL the mean CBFV in the right PCA was significantly lower than that in neonates without PVL at days 10, 14, 21, 28, 42, 56, and 70; the mean CBFV in the left PCA of neonates with PVL was significantly lower than that in those without PVL at days 7, 10, 14, 21, 28, 42, 56, and 70. CBFV measured in neonates without PVL exhibited a gradual increase postnatally. In contrast, CBFV values for neonates with PVL plateaued after day 5 or 7. Conclusions: The serial measurement of PCA CBFV postnatally may prove useful as a predictor of the development of PVL. [ABSTRACT FROM AUTHOR]

Abstract Several studies have noted modest interrater reliability of clinical electroencephalogram (EEG) interpretations. Moreover, no study to date has investigated a means to improve the observed interrater agreement. The purpose of the present study was to examine (i) the interrater reliability of EEG interpretations among three raters (two psychiatrists and one pediatrician); and (ii) how to improve the reliability by establishing a consensus guideline for EEGinterpretation. Three raters, two psychiatrists and a pediatrician, interpreted 100 consecutive EEG recorded at Tajimi General Hospital. After discussing the results of the first trial, the raters established a consensus guideline for EEG interpretation. They then interpreted 50 consecutive EEG recorded at Nagoya City University Hospital following this guideline. Kappa for global judgment of EEG abnormality in three grades (abnormal/borderline/normal) was 0.42 on the first and 0.63 on the second trial. Kappa significantly improved by using the guideline (P = 0.004). It is suggested that discussing and establishing the consensus guideline among the raters offers a feasible method to improve interrater reliability in clinical EEG interpretations. [ABSTRACT FROM AUTHOR]

Abstract Background: The purpose of this study was to evaluate whether or not dopamine (DA) can penetrate to the central nervous system (CNS) from the blood in the infantile period in rats. Methods: In a preliminary experiment, we administered a 50 mg/kg dose of DA hydrochloride, intraperitoneally, to 7-day-old rats (DA 50 mg/kg group), obtaining cerebrospinal fluid (CSF) both before and at 5, 10, 20, 30, 60 and 120 min after administration. The CSF levels of DA and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were then measured. Next, we investigated the DA transfer from blood to the CNS by administering doses of 1, 5, 10 and 30 mg/kg DA hydrochloride (DA 1, 5, 10 and 30 mg/kg groups). In these groups, CSF samples were obtained only at 10 and/or 60 min after DA administration, based on the results of the DA 50 mg/kg group. Results: The DA concentrations in CSF significantly increased compared with values before DA administration in the DA 50 mg/kg group. The DA concentrations in the DA 30 mg/kg group, DOPAC concentrations in the DA 5, 10 and 30 mg/kg groups, and HVA concentrations in all groups were significantly higher than in the control (saline injection) group. Conclusions: These findings suggest easy DA transfer from blood to the CNS and immaturity of the blood–brain barrier for DA in the infantile period in rats. [ABSTRACT FROM AUTHOR]

Unlabelled: In Japan and many other industrialized countries, zinc is readily available as a nutritional supplement, for cosmetic purposes and for the treatment of atopic dermatitis. The potential risks associated with its use are not, however, fully recognized. As a reciprocal relationship exists between copper and zinc, excessive zinc can produce hypocupraemia, which can cause anaemia and neutropenia. We report on a male infant who presented with anaemia and neutropenia and showed signs of developmental delay after dietary restriction for food allergy and eating difficulties and zinc therapy administered for the treatment of atopic dermatitis at a dose nine times the daily dietary allowance for his age group. After 1 mo of zinc withdrawal, copper and ceruloplasmin concentrations had increased, and the blood cell count had improved, activity was increasing but verbal development remained limited. As development improved after withdrawal of zinc, we cannot rule out a relation between developmental delay and hyperzincaemia and/or hypocupraemia.Conclusion: Caution must be exercised in administering zinc to children during their neurological development. [ABSTRACT FROM AUTHOR]

Reports on a girl with Multiple Sclerosis, an autoimmune inflammatory disease of the central nervous system, with onset cerebellar ataxia. Presence of acute disseminated encephalomyelitis (ADEM) in the clinical features; Details on the relapse of ADEM; Findings of electroencephalography and cranial computed tomography.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has epoxide hydrolase activity and phosphatase activity. Our earlier study revealed that lysophosphatidic acids are a substrate of the phosphatase activity of sEH in vitro, but its physiological function remained unknown. Herein, we used the CRISPR/Cas9 system and i‐GONAD method to generate mice that are deficient in sEH phosphatase activity. In the mouse brain, sEH was highly expressed in the olfactory bulb. Deletion of the sEH phosphatase activity resulted in decreased levels of the endocannabinoid 2‐arachidonoyl glycerol (2‐AG), which is a dephosphorylated form of 2‐arachidonoyl‐lysophosphatidic acid in the olfactory bulb. The sEH‐deficient mice showed depressive‐like behavior. These results indicate that sEH can regulate the production of 2‐AG and brain function in vivo. [ABSTRACT FROM AUTHOR]