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AIM This study aimed to evaluate the associations of blood pressure (BP) variability in patients with ischemic stroke during the subacute phase using ambulatory blood pressure monitoring and the ankle-brachial index (ABI). METHODS We retrospectively examined 831 consecutive patients (women 44.8%, mean age 76 ± 12 years) with acute ischemic stroke who underwent 24-h ambulatory blood pressure monitoring during the subacute phase of stroke (median 9 days from onset) and an ABI examination. BP variability was evaluated by assessing the standard deviation and coefficient of variation of systolic BP and diastolic BP. A low ABI was defined as an ABI

Mucinous adenocarcinoma (MAC) rarely occurs in the salivary glands, especially in the labial gland. MACs arising from the salivary glands are characterized by an aggressive behavior due to high invasiveness and a high rate of regional lymph node metastasis. Here, we report a case of MAC arising from the lower lip, shown to have elevated serum carcinoembryonic antigen (CEA) levels by the medical checkup. The tumor showed aggressive behavior and serum CEA levels increased with repeated recurrence. CEA has been shown to have surprisingly diverse functions in cell adhesion, intracellular and intercellular signaling, and complex biological processes such as cancer progression, inflammation, angiogenesis, and metastasis. A MAC arising from the salivary glands may have a poor prognosis because CEA is highly expressed. Generally, serum CEA levels have not been used as tumor markers for salivary gland malignancies; however, it may be useful for MAC arising from salivary glands. We recommend prospective research to determine whether serum CEA estimation is useful as a component of routine pre-treatment workup for MACs arising from the salivary glands.

In myasthenia gravis (MG) patients on intravenous methylprednisolone (IVMP) therapy, initial deterioration should be carefully monitored because it may cause myasthenic crisis. The aim of this study was to investigate the onset, duration and related factors of initial deterioration from the first IVMP in MG patients.A total dose of IVMP in the first cycle of 750 mg or less, over 750 to 1500 mg, and over 1500 to 3000 mg was used in the analysis. Initial deterioration was evaluated in qualitative and quantitative evaluation and was defined as an increase of 2 or more points on the The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale after the start of IVMP therapy in the quantitative evaluation.We enrolled 51 mainly mild MG patients. The mode of onset of initial deterioration from the first IVMP treatment was day 4 in the qualitative and quantitative evaluation. In addition, the mode of duration was 3 days. In multiple logistic regression analysis, factors related to initial deterioration were MGFA classification with overall disease duration up to just before IVMP and thymectomy before IVMP in both the qualitative and the quantitative evaluation (p .001). One to four cycles of IVMP improved the MG-ADL score at hospital discharge from that at the start of IVMP (p .001).Disease severity and thymectomy before IVMP are related to initial deterioration in MG patients. IVMP can be repeated after initial deterioration weekly in most patients.

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.

Thus far, it is well known that increased blood pressure variability may exacerbate stroke outcomes. Blood pressure in the acute phase would be influenced by both reactive hypertension to stroke and intrinsic blood pressure reactivity. Thus, we aimed to evaluate the association between blood pressure variability and outcomes at 3 months using ambulatory blood pressure monitoring in ischemic stroke patients in the subacute phase after reactive hypertension subsided. We retrospectively examined 626 consecutive patients with acute ischemic stroke who underwent 24-hour ambulatory blood pressure monitoring during the subacute phase of stroke (median, 9 days from onset). The variability in blood pressure was evaluated by assessing the standard deviation and coefficient of variation of systolic and diastolic blood pressure. The primary outcome was functional status at 3 months. A poor outcome was defined as a modified Rankin scale score of 3 or more and a good outcome as 2 or less. We assessed the functional outcome at 3 months in 497 patients (79.4%). The mean systolic and diastolic blood pressure levels were not associated with functional outcome. The multivariable analysis revealed that increases in the standard deviations of systolic and diastolic blood pressure, coefficient of variation of diastolic blood pressure, and morning blood pressure surge were associated with poor outcome. Blood pressure variability during the subacute phase of ischemic stroke can be a useful prognostic indicator of poor functional outcome at 3 months in patients with acute ischemic stroke.

Background: The increased blood pressure (BP) variability may influence on the stroke outcome. However, in the acute phase of large stroke, reactive hypertension would occur and sustain for a few days. Therefore, in this phase, it is difficult to understand a cause of BP variability whether it is from reactive hypertension or original blood pressure reactivity. Thus, we aimed to evaluate the association of BP variability using ambulatory blood pressure monitoring (ABPM) in the subacute phase of ischemic stroke, when restoration from reactive hypertension can be observed, with 3-month outcomes. Method: We retrospectively enrolled a consecutive series of 840 patients hospitalized for acute ischemic stroke (55.2% males, age: 76 ± 12 years) performing 24-hour ABPM during the subacute phase of stroke (median 9 days from onset). Variability in BP was evaluated with the standard deviation (SD) and with the coefficient of variation (CV) of systolic (SBP) and diastolic BP (DBP). The primary outcome was evaluated from the 3-month functional status: poor outcome as a modified Rankin Scale score of 3 or more and good outcome as 2 or less. Results: Patients with dipper, non-dipper and riser type were 11.4%, 50.5%, and 38.1%, respectively among the total enrolled cohort. Of these, 651 patients (77.5 %) were assessed for the functional outcomes at 3 months. The rates of patients with poor functional outcome were higher in patients with non-dipper or riser type than in the dipper type (47.7%, 57.1%, and 35.1%, respectively). The mean level of SBP and DBP were not associated with functional outcome. The variability of SBP and DBP was significantly associated with poor functional outcome in univariate analysis. After adjusting for age, sex and initial stroke severity, one increase of SD value (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.03 to 1.13, P Conclusion: The variability of BP in the subacute phase of ischemic stroke is expected to be a useful prognostic factor of a 3-month functional outcome.

Tooth loss, closely associated with malnutrition, increases the risk for cardiovascular disease. The aim of this study was to examine the link between tooth loss, nutritional status, and stroke outcomes.We retrospectively analyzed 195 consecutive patients with acute ischemic stroke who were evaluated for tooth loss. Tooth loss was classified as mild or severe. Nutritional status was evaluated using the Controlling Nutritional Status (CONUT) score. A poor neurologic outcome was defined as a score of 3 to 6 on the modified Rankin Scale at 3 mo post-stroke onset; a score of 0 to 2 was defined as a good outcome.A significant correlation was observed between tooth loss and the CONUT score at admission (ρ = 0.156; P = 0.034). Patients with poor outcomes had higher CONUT scores (P0.001) and a greater frequency of severe tooth loss (P = 0.025). On multivariate analysis, severe tooth loss (odds ratio [OR], 3.93; 95% confidence interval [CI], 1.31-11.8) and the CONUT score (OR, 1.33; 95% CI, 1.02-1.74) were independently associated with poor stroke outcomes.Nutritional status was associated with tooth loss among patients with acute ischemic stroke. Severe tooth loss and a higher CONUT score were independently associated with poor stroke outcomes.

著者人数: 16名, Accepted: 2019-02-21, 資料番号: SA1190003000

UX Orionis stars (UXors) are Herbig Ae/Be or T Tauri stars exhibiting sporadic occultation of stellar light by circumstellar dust. GM\,Cephei is such a UXor in the young ($\sim4$~Myr) open cluster Trumpler\,37, showing prominent infrared excess, emission-line spectra, and flare activity. Our photometric monitoring (2008--2018) detects (1)~an $\sim$3.43~day period, likely arising from rotational modulation by surface starspots, (2)~sporadic brightening on time scales of days due to accretion, (3)~irregular minor flux drops due to circumstellar dust extinction, and (4)~major flux drops, each lasting for a couple of months with a recurrence time, though not exactly periodic, of about two years. The star experiences normal reddening by large grains, i.e., redder when dimmer, but exhibits an unusual "blueing" phenomenon in that the star turns blue near brightness minima. The maximum extinction during relatively short (lasting $\leq 50$~days) events, is proportional to the duration, a consequence of varying clump sizes. For longer events, the extinction is independent of duration, suggestive of a transverse string distribution of clumps. Polarization monitoring indicates an optical polarization varying $\sim3\%$--8$\%$, with the level anticorrelated with the slow brightness change. Temporal variation of the unpolarized and polarized light sets constraints on the size and orbital distance of the circumstellar clumps in the interplay with the young star and scattering envelope. These transiting clumps are edge-on manifestations of the ring- or spiral-like structures found recently in young stars with imaging in infrared of scattered light, or in submillimeter of thermalized dust emission., 20 pages, 9 figures

Context.To investigate the physical properties of the surface layers of small Solar System objects, we take advantage of the phase-angle dependence of the linear polarization degree, which varies with albedo, composition, and other factors. In particular, the angle at which the positive and negative are reversed is a polarimetric parameter known as inversion angle. A group with large inversion angles (the so-called Barbarians) is unusual and is also noteworthy because of their association with meteorites.Aims.We identified an object with such a large inversion angle in the near-Earth asteroids and derived previously unknown parameters, including the maximum polarization degree. By comparing the polarimetric parameters and spectral properties of meteorites, we inferred the surface conditions based on the degree of polarization of the asteroid.Methods.We carried out multiband polarization imaging observations of an L-type near-Earth asteroid, (85989) 1999 JD6, at the Hokkaido University Observatory in 2015 and 2019, covering a wide range of phase angles 30°–105°. Of the polarimetric parameters, we derived the maximum value, inversion angle, and the slope at that angle from the phase angle-polarization degree curve.Results.We found that the inversion angle and the maximum polarization degree of 1999 JD6are 27° and 13%. The inversion angle is significantly larger than those of the majority of all asteroids observed before, but is consistent with that of Barbarian asteroids. 1999 JD6is the first example belonging to this group that is also among the near-Earth asteroids.Conclusions.We claim that 1999 JD6is a member of the Barbarians and has rougher surface particles than lunar regolith.

Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1.

Background Few studies have examined the prevalence of peripheral arterial disease (PAD) with the use of computed tomography angiography (CTA) in patients with acute ischemic stroke (AIS), although several reports have examined its prevalence using an ankle brachial index (ABI). We aimed to determine the prevalence of PAD indicated by CTA in patients with AIS and to clarify the prevalence of PAD in each clinical ischemic stroke subtype. Methods We included 199 consecutive patients with AIS admitted to our hospital and divided them into PAD and non-PAD groups according to the CTA findings. Results Of the 199 patients, 40 (20.1%) had PAD; 27 (67.5%) of the PAD patients were asymptomatic. The prevalence of abnormal ABI (≤.9) was 12.2%. Patients with PAD were older (78.3 ± 10.2 versus 71.5 ± 10.9, P .001) and had a significantly lower ABI value (.89 ± .24 versus 1.15 ± .09, P .001) and higher prevalence of diabetes mellitus (50.0% versus 31.4%, P = .028), atrial fibrillation (40.0% versus 16.4%, P = .001), coronary artery disease (32.5% versus 8.2%, P .001), and intracranial arterial stenosis (47.5% versus 28.9%, P = .025) than patients without PAD. The prevalence of cerebral microbleeds was not different between patients with PAD and those without PAD (25.6% versus 25.4%, P = .985). The prevalence of PAD among ischemic stroke subtypes was highest in patients with cardioembolic infarction (40.5%). Conclusions Almost one fourth of the AIS patients examined had PAD on CTA. Cardioembolic infarction patients showed the highest prevalence of PAD among the clinical ischemic subtypes, suggesting the coexistence of atheromatous diseases and atrial fibrillation.

Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice.

We report the case of a 42-year-old man with chronic hepatitis B virus infection who developed weakness and paresthesia in the extremities 2 months after administration of pegylated interferon (Peg-IFN)α-2a. Nerve conduction studies conducted 6 months after onset showed abnormal temporal dispersions in both tibial nerves. We diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) resulting from treatment with Peg-IFNα-2a. Neurological symptoms were prolonged despite suspension of the treatment. Subsequent treatment with intravenous immunoglobulin improved both clinical symptoms and temporal dispersion. IFNα-induced CIDP is rare, but can reportedly progress even after interruption of IFN-α without immunotherapy. Patients presenting with polyneuropathy after initiation of IFN-α thus require close attention.

We report on optical polarimetric observations of two Apollo type near-Earth asteroids, (422699) 2000 PD3 and (3200) Phaethon, and BVRI photometric observations of 2000 PD3 using the 1.6m Pirka telescope in 2017. We derived the geometric albedo of pv = 0.22 +- 0.06 and the color indices (B-V = 0.282 +- 0.072, V-R = 0.198 +- 0.035 and V-I = 0.203 +- 0.022) for 2000 PD3 which are consistent with those of S-type asteroids (including Q-types). The effective diameter of 2000 PD3 was derived as 0.69 +- 0.15 km using our derived geometric albedo. We found that our polarimetric data of Phaethon in 2017 is deviated from the polarimetric profile taken at different epoch of 2016 using the identical instrument setting (Ito et al., 2018). This result suggests that Phaethon would have a regional heterogeneity in grain size and/or albedo on its surface., Comment: 32 pages, 4 figures, 5 tables accepted for publication in Planetary and Space Science

The near-Earth asteroid (3200) Phaethon is the parent body of the Geminid meteor stream. Phaethon is also an active asteroid with a very blue spectrum. We conducted polarimetric observations of this asteroid over a wide range of solar phase angles α during its close approach to the Earth in autumn 2016. Our observation revealed that Phaethon exhibits extremely large linear polarization: P = 50.0 ± 1.1% at α = 106.5°, and its maximum is even larger. The strong polarization implies that Phaethon’s geometric albedo is lower than the current estimate obtained through radiometric observation. This possibility stems from the potential uncertainty in Phaethon’s absolute magnitude. An alternative possibility is that relatively large grains (~300 μm in diameter, presumably due to extensive heating near its perihelion) dominate this asteroid’s surface. In addition, the asteroid’s surface porosity, if it is substantially large, can also be an effective cause of this polarization., (3200) Phaethon is a near-Earth asteroid discovered in 1983 that has large inclination and eccentricity. Here, the authors perform polarimetric observation of Phaethon over a wide range of solar phase angle and report that the asteroid exhibits a very strong linear polarization.

We present a unique and significant polarimetric result regarding the near-Earth asteroid (152679) 1998 KU$_\mathrm{2}$ , which has a very low geometric albedo. From our observations, we find that the linear polarization degrees of 1998 KU$_\mathrm{2}$ are 44.6 $\pm$ 0.5\% in the R$_\mathrm{C}$ band and 44.0 $\pm$ 0.6\% in the V band at a solar phase angle of 81.0\degr. These values are the highest of any known airless body in the solar system (i.e., high-polarization comets, asteroids, and planetary satellites) at similar phase angles. This polarimetric observation is not only the first for primitive asteroids at large phase angles, but also for low-albedo (< 0.1) airless bodies. Based on spectroscopic similarities and polarimetric measurements of materials that have been sorted by size in previous studies, we conjecture that 1998 KU$_\mathrm{2}$ has a highly microporous regolith structure comprising nano-sized carbon grains on the surface., 9 pages, 5 figures, and 3 tables, accepted for publication in A&A

Background: Malnutrition is an independent risk factor of poor outcome in acute ischemic stroke patients, but the indicator of malnutrition has not been well-established. The Controlling Nutritional Status (CONUT) score is reported to be a useful prognostic value of malnutrition in the cardiovascular diseases and malignant tumors. We investigated the relationship between the CONUT score and functional outcomes in acute ischemic stroke patients. Method: Acute ischemic stroke patients (n=264, 70±12 years old) within 7 days of stroke onset were consecutively studied. The CONUT score was calculated from the serum albumin, total peripheral lymphocyte count and total cholesterol and the CONUT score ≥5 was defined as malnutrition. In the present study, we obtained the blood samples for the CONUT score within 2 days after admission. The primary outcome was evaluated from the 3-month functional status: poor outcome as a modified Rankin Scale (mRS) score ≥ 3 and good outcome as a mRS score Results: Of the total enrolled cohort, 230 patients (87.1%) were assessed for the functional outcomes. The patients with poor outcome (n=85) were older, lower body mass index (BMI), and more frequently had atrial fibrillation, chronic heart failure and anemia, and less frequently had dyslipidemia and current smoking. In addition, the CONUT score and National Institutes of Health Stroke Scale (NIHSS) score at admission were significantly higher in the patients with poor outcome. As the CONUT score was higher, the proportion of patients with poor functional outcome increased, and the poor functional outcome exceed 70% when the score was ≥ 5. Univariate logistic analyses showed that the CONUT score ≥5 was significantly associated with poor outcome at 3 months (odds ratio [OR] 6.05, 95% confidence interval [CI] 2.95-13.09, P Conclusion: The CONUT score at admission is expected to be a useful prognostic marker of a 3-month functional outcome in acute ischemic stroke patients.

A 27-year-old Japanese man ingested methanol. He presented with reduced vision and lost consciousness after 2 days. He became comatose and developed metabolic acidosis, but improved and was discharged after 18 days. A brain magnetic resonance imaging–fluid attenuation inversion recovery sequence showed lesions in the putamen, caudate nucleus and subcortical white matter of both cerebral hemispheres. Magnetic resonance spectroscopy showed a low N-acetylaspartate level, and high choline and lactic acid levels in the right putamen lesion, indicating that recovery coincided with symptom improvement. These magnetic resonance spectroscopy features might reflect the neuronal mitochondrial dysfunction and anaerobic glycolysis caused by the effect of formic acid, a metabolite of methanol.

A standard regimen for ovarian malignant germ cell tumors is bleomycin, etoposide, cisplatin(BEP)chemotherapy. Adherence to a treatment schedule of every 21 days has been reported to be important. However, the incidence of febrile neutropenia( FN)and the optimaluse of granulocyte-colony stimulating factor(G-CSF)are unclear because of the low incidence of ovarian malignant germ cell tumors. We experienced 2 cases of ovarian malignant germ cell tumors that received BEP therapy after fertility-conserving surgery. In 1 case, we delayed drug administration in the first cycle because of FN. However, in order to maintain dose intensity(DI), we performed chemotherapy every 21 days by shortening the rest period. Myelosuppression may be severe in the first cycle of BEP therapy; however, it may be possible to adhere to the treatment schedule by using primary prophylactic administration of G-CSF.

Summary Noda epileptic rats (NERs) present with clinico-pathological manifestations reminiscent of human generalized tonic-clonic epilepsy. Thus, this strain of rat has been a model of primary, generalized, tonic-clonic epilepsy. However, the infrequency of seizures in these rats makes the assessment of antiepileptic drugs (AEDs) difficult. Therefore, traditional AEDs have only been tested in NERs against audiogenic seizures evoked by weekly acoustic priming from 3 to 22 weeks of age or by using the kindling procedure in adult animals. Adult NERs are susceptible to changes in their environment, such as bedding replacement or unpleasant sensory stimuli. In the present study, traditional AEDs—phenobarbital (PB) and sodium valproate (VPA)—were evaluated against seizures evoked by strong environmental stimuli in mature NERs that had not been previously primed. The number of animals presenting with seizures decreased in a dose-dependent manner following administration of either PB (dose range 1.0–5.0 mg/kg) or VPA (50 and 100 mg/kg). Consequently, the utility of NERs as a model of generalized tonic-clonic epilepsy was confirmed. This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs.

In the Fukushima Daiichi Nuclear Power Station, it is necessary to survey the locations and conditions of fuel debris inside reactor pressure vessels or primary containment vessels under water and radiation environment in preparation for removing fuel debris. An optical fiber is well known for features such as signal transmission, light weight, superior insulation performance, water resistance and electromagnetic noise resistance. These features allow the optical fiber to simplify the instrumentation systems for in-vessel inspection, as long as provide that the optical fiber can be used under high radiation dose environment. The radiation resistance of an optical fiber was improved by increasing the amount of hydroxyl up to 1000 ppm in pure silica fiber. The improved optical fibers were irradiated with γ-ray up to 1 × 106 Gy using a 60Co source. They indicated a large peak around 600 nm and a peak tail from ultraviolet region, but no large absorption in infrared region except a hydroxyl absorption peak of...

We herein report two cases of acute ischemic stroke associated with iron deficiency anemia (IDA) due to bleeding from uterine fibroids. Anemia is not generally recognized as a risk factor for stroke. The physiological mechanisms that may factor in the development of ischemic stroke in patients with IDA include thrombocytosis, hypercoagulable state, and anemic hypoxia. In our two cases, IDA was considered to be the cause of ischemic stroke because all other known causes of stroke were ruled out. In patients with ischemic stroke due to anemia, early treatment of the anemia is important to prevent stroke recurrence.

Context. CH Cyg is one of the most studied symbiotic stars. Its properties, however, are still not well known. Two main periods, about 15 years and 750 days, are known in the photometric and spectroscopic variations, and two models are proposed for these origins. One is a binary system with an orbital period of 15 years consisting of a hot component and pulsating red giant with a 750-day period. The other is a triple system consisting of an inner symbiotic binary with an orbital period of about 750 days and third component with an orbital period of 15 years. Several active stages have been observed since the 1970s during which the object brightened up by ΔU = 3−5 mag and prominent emission lines appeared. Large mass outflows were observed at some active stages. Aims. The spectral variation of CH Cyg has been monitored at Asiago Observatories to understand the problems mentioned above. We have analysed spectra obtained in the time period from 1995 to 2004 which covers an active stage during the years 1998−2000. Methods. High- and low-resolution optical spectra obtained at the Asiago Observatories are used. Results. Narrow absorption lines of Fe I, Cr I, Ti I, and so on appeared in 1998 at an early phase of the active stage. These lines are clearly distinguished from those of the M-type giant and are typically found on the spectrum of early A-type dwarfs. They were redshifted by about 30 km s−1 with respect to the absorption lines of the M-type giant. Assuming that their radial velocities represent the orbital motion of the hot component, its semi-amplitude is estimated to be 37.0 ± 0.5 km s−1. The masses of the hot component and the M-type giant are estimated to be 0.32 ± 0.02 M⊙ and 4.6 ± 0.2 M⊙, respectively, where a circular orbit with a period of 756 days is adopted. If the inner binary system has an elliptical orbit, e = 0.33, and a period of 750.1 days, the masses of the two components are 0.21 ± 0.01 M⊙ and 2.2 ± 0.1 M⊙, respectively. Our results lend support to the triple system model, because if the period of the symbiotic binary were 15 years, the mass of the hot component would be expected to exceed the Chandrasekhar limit. Highly blueshifted absorption components of H I and He I lines appeared at a later phase of the active stage. Mass ejections with velocities on the order of 1000 km s−1 seem to have occurred along the orbital plane from December 1998 to March 1999. The highest outflow velocity, − 2383 km s−1, was observed on 1999 February 26. Narrow absorption components of Na I D1, D2, and Fe II lines redshifted by 10−15 km s−1 coexisted with the highly blueshifted broad absorption components of H I and He I lines. This phenomenon might have been related to an inner disc inflow expected in wind-compressed discs. In contrast to the bipolar mass outflows at the past active stages, high-velocity equatorial mass ejections likely occurred at the active stage during the years 1998−2000. There should have been an eclipse of the hot component by the M-type giant in the inner binary system in the time period of December 1998 to January 1999. A clear light curve of the eclipse, however, was not detected. Possibly, the luminosity of the hot component was due mainly to free-free emission from the ejected circumstellar matter which was likely more extended than the M-type giant. On the other hand, another eclipse by the third component with the period of 15 years began at the end of May 1999 during which the hot component as well as the emitting regions of Hβ and Fe II lines were well eclipsed. The obscuring matter around the third component should have been much more extended than the M-type giant, and it was likely semi-transparent, because the spectrum of the M-type giant was well seen during the eclipse. The third component appears to be similar to the invisible secondary component in the long-period eclipsing binary ϵ Aur.

We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.

With the aim of discovering potent inhibitors of the p53-MDM2 interaction and thus obtaining a potent anticancer drug, we have pursued synthesis and optimization of dihydroimidazothiazole derivatives, which have been discovered via scaffold hopping by mimicing the mode of interaction between MDM2 and Nutlins. Upon the discovery we encountered a problem involving the chemical instability of the scaffold, that is, susceptibility to oxidation which led to imidazothiazole. In order to solve this problem and to obtain further potent compounds, we executed medicinal research and thus furnished the optimal compounds by incorporating the methyl group onto the C-6 position to avoid the oxidation, and by modifying the C-2 moiety of the additional proline motif, which furnished high potency. The incorporation of the pyrrolidine moiety at the C-2 position raised another hydrophobic interaction site with MDM2 protein, which was generated by the induced-fitting observed by co-crystal structure analysis. These optimal molecules showed significant improvement in potency when compared with the early lead (+)-1 or Nutlin-3a.

About three weeks after successful coil embolization of a basilar apex aneurysm, a 66-year-old woman developed occipital headaches. T2 and FLAIR MRI brain images demonstrated multiple new hyperintense lesions in the posterior circulation territory including cerebellum, right superior cerebellar peduncle, left thalamus and bilateral temporo-occipital lobes and she was subsequently hospitalized. Findings suggestive of other underlying disease were not observed, although an increased protein level was noted in cerebrospinal fluid (69 mg/dl). Headache and clinical findings improved approximately 12 weeks after coil embolization. MRI findings also showed improvement. These clinical and radiological findings made this patient a distinctive case of posterior reversible encephalopathy syndrome (PRES) associated with coil embolization suggesting that clinicians should be aware that PRES can present as comparatively mild symptoms several weeks after coil embolization.

Objective: To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients. Methods: A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured. Results: Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were

Case Report A 66-year-old man with acute ischemic stroke in the setting of lung adenocarcinoma developed acute-onset deep vein thrombosis (DVT) of the lower limbs after changing to warfarin from a heparin combination. The diagnosis of warfarin-resistant DVT was established based on the laboratory data and clinical evaluation. Heparin administration resulted in good control of thrombin regulation. Cancer patients are at high risk of venous thromboembolism, and the combination of these 2 conditions is known as Trousseau's syndrome. Conclusion Our report suggests that heparin administration may provide good control of thromboembolic events, although there is no established medical treatment to extend the survival of patients with Trousseau's syndrome.

We report spectroscopic observations of the resonance lines of singly ionized $^{7}$Be in the blue-shifted absorption line systems found in the post-outburst spectra of two classical novae -- V5668 Sgr (Nova Sagittarii 2015 No.2) and V2944 Oph (Nova Ophiuchi 2015). The unstable isotope, $^{7}$Be, should has been created during the thermonuclear runaway (TNR) of these novae and decays to form $^{7}$Li within a short period (a half-life of 53.22 days). Confirmations of $^{7}$Be are the second and the third ones following the first case found in V339 Del by Tajitsu et al. (2015). The blue-shifted absorption line systems in both novae are clearly divided into two velocity components, both of which contain $^{7}$Be. This means that the absorbing gases in both velocity components consist of products of TNR. We estimate amounts of $^{7}$Be produced during outbursts of both novae and conclude that significant $^{7}$Li should have been created. These findings strongly suggest that the explosive production of $^{7}$Li via the reaction $^{3}$He($\alpha$,$\gamma$)$^{7}$Be and subsequent decay to $^{7}$Li occurs frequently among classical novae and contributes to the process of the Galactic Li enrichment., Comment: 8 pages, 6 figures, accepted for publication in ApJ

Starting with Nutlins as an initial lead, we designed and generated bicyclic scaffolds aiming to place cis-bischlorophenyl moiety at the equivalent location where the hydrophobic interaction with MDM2 could be expected. As a result, we discovered novel MDM2 inhibitors possessing a dihydroimidazothiazole scaffold. Further exploration of the side chains on the dihydroimidazothiazole scaffold aided by molecular modeling resulted in compounds exhibiting almost comparable in vitro potency to Nutlin-3a.

We previously reported on a series of cyclohexanediamine derivatives as highly potent factor Xa inhibitors. Herein, we describe the modification of the spacer moiety to discover an alternative scaffold. Ethylenediamine derivatives possessing a substituent at the C1 position in S configuration and phenylenediamine derivatives possessing a substituent at the C5 position demonstrated moderate to strong anti-fXa activity. Further SAR studies led to the identification of compound 30 h which showed both good in vitro activity (fXa IC(50) = 2.2 nM, PTCT2 = 3.9 μM) and in vivo antithrombotic efficacy.

th periodic inspection of the experimental fast reactor Joyo of the Japan Atomic Energy Agency, the irradiation test subassembly (S/A) was bent and became an obstruction in the reactor vessel (R/V), and the upper core structure (UCS) was damaged. This incident made it necessary to perform an in-vessel visual inspection using an optical fiber scope. This inspection revealed that the UCS needed to be replaced for Joyo re-start. A critical task in restoring Joyo was evaluating the activation of the UCS; this was necessary to design the transportation cask for the damaged UCS. However, it is difficult to directly obtain samples of the highly irradiated components in the R/V. In order to obtain experimental data and to evaluate the accuracy of radiation dose calculation, in-vessel gamma dose rate measurements were conducted in the experimental fast reactor Joyo. The measured gamma dose rate was compared with the values calculated using the QAD code and the ORIGEN2 code with the JENDL-3.2 cross section library.

To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD).This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated.We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible.IFX might be an effective and tolerable treatment for refractory KD.

Methanesulfonamides were deprotected to their parent amines via deprotonation and oxygenation with O(2) (g), even in the presence of other traditional sulfonamides.

グラビアインキにおける顔料分散を考えるうえで，グラビア印刷，包装フィルムといった関係分野の知識は必須であり，単に顔料を樹脂中に均一に分散すればよいといったわけではない。グラビアインキは印刷して使用されるため各種印刷適性や被膜物性，後加工適性が必要であり，インキ製造においてもこれらに留意する必要がある。分散安定化においては適切な分散条件，酸塩基の概念に基づく吸着，そして分散剤使用による立体障害効果が重要である。

Choledochoceleは先天性胆道拡張症のなかでもまれな疾患である．症例は81歳の男性で，心窩部痛を主訴に当院紹介となった．腹部CT，MRCPで下部胆管に嚢胞状拡張を認め，上部消化管内視鏡検査で乳頭口側に20 mm大の半球状隆起と乳頭に顆粒状変化を認めた．乳頭の生検ではtubular adenomaが検出され，十二指腸乳頭腺腫を合併したcholedochoceleの診断にて，経十二指腸的乳頭切除術，総胆管嚢腫切除術を施行した．Choledochoceleの治療においては嚢腫内の胆汁うっ滞の解除を目的に内視鏡的乳頭切開などの非手術的治療がまず考慮される場合が多いが，本例では十二指腸乳頭部腺腫を合併しており乳頭部腺腫の切除と嚢腫の開放を確実に行う目的で開腹手術を選択した．Choledochoceleにおいても少数ながら癌合併例も報告されており，手術的または非手術的な治療後も定期的な経過観察が必要と考えられた．

Maltosides of butanol, octanol, and lauryl alcohol were found for the first time to serve as substrates for cyclomaltodextrin glucanotransferase (CGTase), and glycosyl residue was transfered from dextrin to the substrate affording novel maltosides with 3-4 glucose units.

Bifidobacterium属は,高いプロバイオティクス効果および細菌の分類学のモデルケースとして興味深い状況にある。(独)理化学研究所バイオリソースセンター微生物材料開発室(JCM)に保存されているBifidobacterium属およびその近縁種で,ヒトを分解源とする基準株を検索したところ,9菌種(菌株)が候補としてあげられ,その全ゲノム解析を開始した。その菌種は,Table 1に示したとおりであるが,B. bifidum, B. breveおよびB. catenulatumの3菌種は全ゲノム配列を決定し,B. dentium, P. denticolens, S. inopinataおよびG. vaginalisの3菌種は,コンティグが15前後になっており,B. longumおよびb. scarcoviiについては,ショットガンライブラリの作製を完了した。各菌株について引き続きシークエンス作業を進め,全ゲノム解析後は,大規模なBifidobacterium属の比較ゲノム解析を行う予定である。, It is interested in Genus Bifidobacterium shows the probiotic effects and as the model case of taxonomy. The nine species of Bifidobacterium and the closest related species of the type strains isolated from human origin were obtained from the Microbe Division, Japan Collection of Microorganisms (JCM), RIKEN BioResource Center. We have started sequencing of the complete genome of nine species. We have done the complete genome sequencing of B. bifidum, B. breve and B. catenulatum. The contigs of Parascardovia denticolens, Scardovia inopinata and Gardnerella vaginalis is less than fifteen. The draft sequences of B. dentium genomes have been obtained, and the shotgun library of the B. scardovii and B. longum genomes were prepared. We are going to widely comparative genomics in the Family Bifidobacteriaceae, when all the genomes will be finished.

Stereoselective preparation of unsymmetrically protected 2-alkylidene-1,3-imidazolidines was achieved by the reaction of N,N′-protected ethylenediamine, bromopropynamide, and K3PO4 in hot DMF. When N-protected aminoethanol was used in place of the protected ethylenediamine, an oxazolidine derivative was produced.

Recent photometric and spectroscopic observations of Pleione are reported. Pleione showed brightness declines in both the B and V bands by � 0 m .2 5b etween 2006 January and 2007 March. Significant decreases in the strengths and widths of the long-lived emission components in H˛ and Hwere observed during this period, while additional outer double-emission components appeared in these lines. Many metallic shell lines strengthened during the observation period, being accompanied by central quasi-emission components. W ei nterpret these spectral changes in terms of a double disk: the progressive decline of a misaligned old disk in due course of precession and the formation and growth of a new disk in the star's equatorial plane.

我々は,Lactobacillus reuteri JCM 1112^T, Lactobacillus fermentum IFO 3956, Lactococcus garvieae(ブリに対する毒性株), Lactococcus garvieae(ブリに対する無毒株)およびLactobacillus rhamnosusの全ゲノム解析を完了した。そして,Bifidobacterium breve, Bifidobacterium bifidumおよびBifidobacterium catenulatumについては,全ゲノム配列を決定中である。プロバイオティクスとは,"宿主の健康に対して貢献する生きた微生物"と定義付けられている。本プロジェクトでは,L.reuteriのプロバイオティクス効果を分子レベルで解明することを目的としている。そこで,分類学的にL.reuteriと近縁であるにもかかわらず,プロバイオティクス効果のほとんど認められないL.fermentumについても全ゲノム解析を行った。両菌種の比較ゲノム解析の結果,L.reuteriのゲノムには,抗菌物質であるロイテリン合成系にかかわる遺伝子の48kbの"genomicisland"を有しており,哺乳動物の腸内フローラバランスに良い影響を及ぼしていると推察された。我々は,glycerol dehydratase subunit motif(PFAM PFO2286-PFO2288)として,L.reuteriゲノムに3つの遺伝子(LR1633-LR1635)を検出し,gupCDE(glycerol utilizing enzymes)と命名した。本研究では,そのgupCDE遺伝子破壊候補株(L.reuteri Δ gupCDE)を得て,PCR解析やglycerol dehydratase酵素活性などから,L.reuteri Δ gupCDEを認めた。今後,親株(L.reuteriJCM1112^T株)とL.reuteri Δ gupCDEのそれぞれノトバイオート(モノアイソレート)マウスを解析して,プロバイオティクス効果を明らかにしていく予定である。, We determined the complete genome sequences of Lactobacillus reuteri JCM 1112^T, Lactobacillus fermentum IFO3956, Lactococcus garvieae (a toxic strain for yellowtail), Lactococcus garvieae (a non-toxic strain for yellowtail) and Lactobacillus rhamnosus.The genome analysis of Bifidobacterium breve, Bifidobacterium bifidum and Bifidobacterium catenulatum is on going. Probiotics are live microorganisms that confer health benefits on the host. The probiotic L. reuteri and non-probiotic L.fermentum are phylogenetically closest to L.reuteri in the Lactobacillus. To elucidate the molecular basis on the probiotic property exhibited by L.reuteri, comparative analysis of both genomes showed that L.reuteri harbored the unique 48kb genomic island containing the genes necessary for the biosynthesis of a reactive 3-hydroxypropionaldehyde (reuterin), which may influence the microflora balance in the gut. We identified three genes (LR1633-LR1635) with a glycerol dehydratase subunit motif (PFAM PF02286-PF02288) in the L.reuteri genome. These genes are designated gupCDE (glycerol utilizing enzymes) in this study. The gupCDE knock-out L.reuteri (L.reuteri Δ gupCDE) was obtained, and the reuterin synthesis will be conducted by glycerol dehydratase in the glycerol metabolism in vivo by the gnotobiotic mice mono-associated with L.reuteri and L.reuteri Δ gupCDE.

We have published p53-MDM2 interaction inhibitors possessing a novel dihydroimidazothiazole scaffold. Although our lead compound 1 showed strong antitumor activity with single oral administration on a xenograft model using MV4-11 cells harboring wild-type p53, it needed a higher dose (200mg/kg) for distinct efficacy. We executed further optimization with the aim of improvement of potency and physicochemical properties. Thus optimal compounds were furnished by introducing fluorine moieties onto the phenyl ring at the C-6 position and the pyrrolidine part at the C-2 substituent; and modifying the terminal piperazine to 4,7-diazaspiro[2,5]octane variants. Furthermore, replacing 4-chlorophenyl on the C-5 position with pyridyl variant decreased nonspecific cytotoxicity significantly. Our exploration afforded DS-5272 indicating excellent antitumor efficacy from a dose of 25mg/kg on SJSA-1 xenografted models with high safety and good PK profiles, which has appropriate potency as a clinical candidate.

The origin of lithium (Li) and its production process have long been an unsettled question in cosmology and astrophysics. Candidates environments of Li production events or sites suggested by previous studies include big bang nucleosynthesis, interactions of energetic cosmic rays with interstellar matter, evolved low mass stars, novae, and supernova explosions. Chemical evolution models and observed stellar Li abundances suggest that at least half of the present Li abundance may have been produced in red giants, asymptotic giant branch (AGB) stars, and novae. However, no direct evidence for the supply of Li from stellar objects to the Galactic medium has yet been found. Here we report on the detection of highly blue-shifted resonance lines of the singly ionized radioactive isotope of beryllium, $^{7}$Be, in the near ultraviolet (UV) spectra of the classical nova V339 Del (Nova Delphini 2013). Spectra were obtained 38 to 48 days after the explosion. $^{7}$Be decays to form $^{7}$Li within a short time (half-life 53.22 days). The spectroscopic detection of this fragile isotope implies that it has been created during the nova explosion via the reaction $^{3}\mbox{He}(\alpha,\gamma)^{7}\mbox{Be}$, and supports the theoretical prediction that a significant amount of $^{7}$Li could be produced in classical nova explosions. This finding opens a new way to explore $^{7}$Li production in classical novae and provides a clue to the mystery of the Galactic evolution of lithium., Comment: 28 pages, 6 figures, published in Nature