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Medication adherence is important for the appropriate drug-based treatment in patients with chronic diseases, especially those with cardiovascular diseases (CVDs). The purpose of the present study was to evaluate medication adherence among patients with CVDs using subjective and objective measurements. We enrolled outpatients who visited Fukuoka University Chikushi Hospital from June to December 2022. As a subjective measurement, we used a self-reported questionnaire developed by Ueno et al., which consists of 12 questionnaire items grouped into the following four domains: medication compliance (subjective compliance), collaboration with health care providers (collaboration), willingness to access and use information about medication (willingness), and acceptance to take medication and how taking medication fits a patient's lifestyle (acceptance). The pill counting method was used as an objective measurement to calculate the medication adherence rate; Poor Adherence was defined as a medication adherence rate of <100%. Ninety-four patients were analyzed. No statistically significant differences were observed between the patients in the Good and Poor Adherence groups classified by pill counting, an objective indicator; in the subjective evaluation index Ueno scale scores of subjective compliance, collaboration, willingness, and acceptance domains; and in the total score. A multivariate analysis revealed that obesity (odds ratio, 3.527; 95% confidence interval, 1.387-9.423; p = 0.008) was an independent factor associated with Poor Adherence. In conclusion, we found a discrepancy between subjective and objective measurements for the evaluation of medication adherence. Furthermore, obesity was an independent factor associated with poor medication adherence assessed by the pill counting method; thus, patients with CVD and obesity require a careful follow-up.

Globisporangium spp. are soil-inhabiting oomycetes distributed worldwide, including in polar regions. Some species of the genus are known as important plant pathogens. This study aimed to clarify the species construction of Globisporangium spp. and their long-term isolation pattern in Sanionia moss in Ny-Ålesund, Spitsbergen Is., Norway. Globisporangium spp. were isolated at two-year intervals between 2006 and 2018 at a Sanionia moss colony, Ny-Ålesund, Spitsbergen Is., Norway. The isolates were obtained by using three agar media and were identified based on sequences of the rDNA-ITS region and cultural characteristics. Most of the Globisporangium isolates obtained during the survey were identified into six species. All six species were grown at 0 °C on an agar plate and used to infect Sanionia moss at 4 and/or 10 °C under an in vitro inoculation test. The total isolation frequency of Globisporangium gradually decreased throughout the survey period. The isolation frequency varied among the six species, and four of the species that showed a high frequency in 2006 were rarely isolated after 2016. The results suggested that Globisporangium inhabiting Sanionia moss in Ny-Ålesund has a unique composition of species and that most of the species reduced their population over the recent decade.

The partition efficiency of the double-spaced coil for eccentric and toroidal coils on countercurrent chromatographic separation of proteins was evaluated using the small-scale cross-axis coil planet centrifuge (CPC) equipped with circular and elliptic cylindrical columns. Standard cytochrome c, myoglobin and lysozyme samples were used for separation with the 12.5% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate system. In the circular column, the double-spaced eccentric coil yielded better peak resolution than the double-spaced toroidal coil, and the double-spaced eccentric coil yielded better peak resolution than the single-spaced eccentric coil. In the elliptic column, the double-spaced eccentric coil also produced better peak resolution than the double-spaced toroidal coil, but the single-spaced eccentric coil yielded better peak resolution than the double-spaced eccentric coil. The overall results indicated that the double-spaced eccentric coil for the circular column and the single-spaced eccentric coil for the elliptic column yielded better protein separation using the small-scale cross-axis CPC with aqueous two-phase solvent systems.

The soricid water shrew Chimarrogale platycephalus is a mammalian species endemic to the Japanese Islands. The animals inhabit the islands of Honshu and Kyushu, and are considered to be extinct in Shikoku. Information on this water shrew from Honshu and Kyushu is scarce, and C. platycephalus is registered on many local governments' red lists as an endangered species. There are very few studies on their ethology, ecology or phylogenetics, due to difficulties related to the shrews being both nocturnal and aquatic: to study C. platycephalus, field research must be conducted in mountain streams at night. To overcome these challenges, we previously established a genetic analysis method using the feces of C. platycephalus, as a result of which the amount of phylogenetic and phylogeographic data has increased and our understanding of the species has improved. In this study, microsatellite markers were developed, and analyses using markers for 21 loci were performed. Moreover, to confirm the ability of these 21 microsatellite markers to differentiate individuals, all markers were tested using fecal and tissue specimens from 12 individuals reared separately in an aquarium. Using as few as 12 of these loci, individual differentiation with 100% accuracy should be achievable. The development of microsatellite markers in this study and the establishment of individual identification methods should greatly contribute to future ecological, ethological, population genetics and biogeographical research on C. platycephalus.

Background: Inappropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical safety and efficacy; however, little is known about clinical data associated with an inappropriate DOAC dosing in Japan. In addition, there is no report in which the appropriateness of DOAC dosing between prescription for inpatients and for outpatients was examined. In this study, we aimed to investigate the prevalence and factors associated in the inappropriate dosing of DOACs in patients with atrial fibrillation (AF)., Methods: The retrospective cohort study was conducted at a single Japanese university hospital. Both inpatients and outpatients, who were diagnosed with AF and for whom treatment with either dabigatran, rivaroxaban, apixaban, or edoxaban was initiated between April 1, 2014 and March 31, 2018, were enrolled in the study. Appropriateness of DOAC dosing was assessed according to the manufacturer's labeling recommendations (dose reduction criteria) of each DOAC. Inappropriate reduced dose, namely, underdosing, was defined as prescription of a reduced dose of DOAC despite the patient not meeting the dose reduction criteria. Inappropriate standard dose, namely, overdosing, was defined as prescription of a standard dose of DOAC despite the patient meeting the dose reduction criteria. Inappropriate DOAC dosing was defined as a deviation of the recommended dose (both underdosing and overdosing)., Results: A total of 316 patients (dabigatran, 28; rivaroxaban, 107; apixaban, 116; and edoxaban, 65) were included, with a median (interquartile range) age of 75 (66-81) years and 62.3% male. DOACs were prescribed at an appropriate standard dose in 39.2% of patients, an appropriate reduced dose in 36.7%, an inappropriate standard dose in 2.5%, and an inappropriate reduced dose in 19.3%. Multivariate analysis revealed that the inappropriate dosing of DOACs was significantly associated with prescriptions for outpatients (vs. inpatients; odds ratio [OR] 2.87, 95% confidence interval [CI] 1.53-5.62, p  < 0.001) and those with higher HAS-BLED scores (OR 1.87, 95% CI 1.42-2.51, p < 0.001)., Conclusions: Our results demonstrated that the inappropriate dosing of DOACs occurred in approximately 20% of AF patients, and was more frequent in outpatients (vs. inpatients) and in those with a higher risk of bleeding. It is recommended that pharmacists play a greater role in assisting in the prescription process to help physicians make better decisions., Competing Interests: Competing interestsThe author(s) declare no competing interests., (© The Author(s). 2020.)

The partition efficiencies of three different coiled columns, conventional multilayer coiled column, eccentric coiled column and toroidal coiled column, were evaluated by the separation of 4-methylumbelliferyl sugar derivatives using the coil satellite centrifuge (CSC) with an organic-aqueous two-phase solvent system composed of ethyl acetate/1-butanol/water. The CSC apparatus was reinforced the planet axis to maintain the stable satellite motion, which was completed by combining the rotation of three axes including the sun axis (the angular velocity, ω 1 ), the planet axis (ω 2 ) and the satellite axis (ω 3 ) under the relation at ω 1 = ω 2 + ω 3 . In the present study, four different rotation speed combination types were used for the separation at the ratio (ω 1 , ω 2 , ω 3 ) = I. (300, 150, 150), II. (300, 100, 200), III. (300, 147, 153) and IV. (300, 200, 100 rpm) under different revolution speeds of ω 1  = 300, 400 and 500 rpm. In the conventional multilayer coiled column with the upper mobile phase, the rotation speed combination type II yielded the best peak resolution while the rotation speed combination types III and IV had extremely low stationary phase retention even at higher revolution speeds. This inconvenience was eliminated by using the eccentric and the toroidal coiled column. The rotation speed combination type II for the eccentric coiled column and the type IV for the toroidal coiled column produced the best separation in both the upper and the lower mobile phases among four different rotation speed combination types. The overall results indicated that better peak resolution was obtained by the eccentric coiled column than by the toroidal coiled column except for the separation with the upper mobile phase at the low revolution speed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Coil satellite centrifuge (CSC) produces the complex satellite motion consisting of the triplicate rotation of the coiled column around three axes including the sun axis (the angular velocity, ω 1 ), the planet axis (ω 2 ) and the satellite axis (the central axis of the column) (ω 3 ) according to the following formula: ω 1 =ω 2 +ω 3 . Improved peak resolution in the separation of 4-methylumbelliferyl sugar derivatives was achieved using the conventional multilayer coiled columns with ethyl acetate/1-butanol/water (3: 2: 5, v/v) for the lower mobile phase at the combination of the rotation speeds (ω 1 , ω 2 , ω 3 )=(300, 150, 150rpm), and (1:4:5, v/v) for the upper mobile phase at (300:100:200rpm). The effect of the satellite motion on the peak resolution and the stationary phase retention was evaluated by each CSC separation with the different rotation speeds of ω 2 and ω 3 under the constant revolution speed at ω 1 =300rpm. With the lower mobile phase, almost constant peak resolution and stationary phase retention were yielded regardless of the change of ω 2 and ω 3 , while with the upper mobile phase these two values were sensitively varied according to the different combination of ω 2 and ω 3 . For example, when ω 2 =147 or 200rpm is used, no stationary phase was retained in the coiled column while ω 2 =150rpm could retain enough volume of stationary phase for separation. On the other hand, the combined rotation speeds at (ω 1 , ω 2 , ω 3 )=(300, 300, 0rpm) or (300, 0, 300rpm) produced insufficient peak resolution regardless of the choice of the mobile phase apparently due to the lack of rotation speed except at (300, 0, 300rpm) with the upper mobile phase. At lower rotation speed of ω 1 =300rpm, better peak resolution and stationary phase retention were obtained by the satellite motion (ω 3 ) than by the planetary motion (ω 2 ), or ω 3 >ω 2 . The effect of the hydrophobicity of the two-phase solvent systems on the stationary phase retention was further examined using the n-hexane/ethyl acetate/1-butanol/methanol/water system at different volume ratios. In the satellite motion at (ω 1 , ω 2 , ω 3 )=(300, 150, 150rpm), almost constant stationary phase retention was obtained with the lower mobile phase regardless of the hydrophobicity of the solvent system whereas the stationary phase retention varied according to the volume ratio of the two-phase solvent system for the upper mobile phase. However, stable stationary phase retention was observed with either phase used as the mobile phase. In order to analyze the acceleration acting on the coiled column, an acceleration sensor was set on the column holder by displacing the multilayer column. The combination of the rotation speeds at (300, 100, 200rpm) showed double loops in the acceleration track, whereas (300, 150, 150rpm) showed a single loop, and all other combinations showed, complex tracks. The overall results indicate that the satellite motion is seriously affected by the combination of rotation speeds and the hydrophobicity of the two-phase solvent system when the upper phase was used as the mobile phase for separation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A new high-speed counter-current chromatograph, named coil satellite centrifuge (CSC), was designed and fabricated in our laboratory. The CSC apparatus produces the satellite motion such that the coiled column simultaneously rotates around the sun axis (the angular velocity, ω1), the planet axis (ω2) and the satellite axis (the central axis of the column) (ω3). In order to achieve this triplicate rotary motion without twisting of the flow tube, the rotation of each axis was determined by the following formula: ω1=ω2+ω3. This relation enabled to lay out the flow tube without twisting by the simultaneous rotation of three axes. The flow tube was introduced from the bottom side of the apparatus into the sun axis of the first rotary frame reaching the upper side of the planet axis and connected to the column in the satellite axis. The performance of the apparatus was examined on separation of 4-methylumbelliferyl (MU) sugar derivatives as test samples with organic-aqueous two-phase solvent systems composed of ethyl acetate/1-butanol/water (3:2:5, v/v) for lower phase mobile and (1:4:5, v/v) for upper phase mobile. With lower phase mobile, five 4-MU sugar derivatives including β-D-cellobioside (Cel), β-D-glucopyranoside, α-D-mannopyranoside, β-D-fucopyranoside and α-L-fucopyranoside (α-L-Fuc) were separated with the combined rotation around each axis at counterclockwise (CCW) (ω1) - CCW (ω2) - CCW (ω3) by the flow tube distribution. With upper phase mobile, three 4-MU sugar derivatives including α-L-Fuc, β-D-galactopyranoside and Cel were separated with the combined rotation around each axis at clockwise (CW) (ω1) - CW (ω2) - CW (ω3) by the flow tube distribution. A series of experiments on peak resolution and stationary phase retention revealed that better partition efficiencies were obtained at the flow rate of 0.5 mL/min (column 1) and 0.8 mL/min (column 2) for lower phase mobile and 0.2 mL/min (column 1) and 0.4 mL/min (column 2) for upper phase mobile when using the left-handed multilayer coil (total capacity: 57.0 mL for column 1 and 75.0 mL for column 2) under the rotation speeds of approximately ω1=300 rpm, ω2=150 rpm and ω3=150 rpm., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Oomyceteous snow molds, Pythium species, were reported to be less tolerant to chilling and freezing temperatures than other snow mold taxa. However, Pythium species are often found to be pathogenic on mosses in Polar Regions. We investigated the frost resistance of Pythium species from Temperate (Hokkaido, Japan) and Subantarctic Regions. Free mycelia and hyphal swellings, structures for survival, of Pythium iwayamai and Pythium paddicum lost viability within freeze-thaw 3 cycles; however, mycelia in host plants survived the treatment. It was reported that fungi in permafrost are characterized both by the presence of natural cryoprotectants in these ecotopes and by the ability to utilize their inherent mechanisms of protection. It is conceivable that plant substrates or derivatives thereof are natural cryoprotectants, enabling them to provide advantageous conditions to microorganisms under freezing conditions. Our results are the first to experimentally support this hypothesis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Protein separation was performed using the high-speed countercurrent chromatograph (HSCCC) at both synchronous and nonsynchronous type-J planetary motions. The partition efficiency was evaluated with two different column configurations, eccentric coil and toroidal coil, on the separation of a set of stable protein samples including cytochrome C, myoglobin and lysozyme with a polymer phase system composed of 12.5% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate. Better peak resolution was obtained by the eccentric coil than by the toroidal coil using either lower or upper phase as the mobile phase. The peak resolution was further improved using the eccentric coil by the nonsynchronous type-J planetary motion with the combination of 1066 rpm of column rotation and 1000 rpm of revolution.

A new design of universal high-speed counter-current chromatograph (HSCCC) was fabricated in our laboratory. It holds a set of four column holders symmetrically around the rotary frame at a distance of 11.2cm from the central axis. By engaging the stationary gear on the central axis of the centrifuge to the planetary gears on the column holder shaft through a set of idle gears, two pairs of diagonally located column holders simultaneously rotate about their own axes in the opposite directions: one forward (type-J planetary motion) and the other backward (type-I planetary motion) each synchronously with the revolution. Using the eccentric coil assembly, partition efficiencies produced by these two planetary motions were compared on the separation of two different types of sugar derivatives (4-methylumbelliferyl and 5-bromo-4-chloro-3-indoxyl sugar derivatives) using organic-aqueous two-phase solvent systems composed of n-hexane/ethyl acetate/1-butanol/methanol/water and aqueous 0.1M sodium tetraborate, respectively. With lower phase mobile, better peak resolution was obtained by the type-J forward rotation for both samples probably due to higher retention of the stationary phase. With upper phase mobile, however, similar peak resolutions were obtained between these two planetary motions for both sugar derivatives. The overall results indicate that the present universal HSCCC is useful for counter-current chromatographic separation since each planetary motion has its specific applications: e.g., vortex CCC by the type-I planetary motion and HSCCC by the type-J planetary motion both for separation of various natural and synthetic products., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Enantioselective total synthesis of the labdane diterpene (-)-1, was achieved starting from the R-(-)-enantiomer of the Wieland-Miescher ketone. The enantiomer (+)-1 was obtained by partial synthesis via microbial transformation of sclareol. These results established that the natural compound (+)-1, a platelet aggregation inhibitor, has a normal absolute stereochemistry like that of manool. The B-norlabdane-related compound 44 was also synthesized using a novel ring contraction reaction.

The 90% methanol-soluble fraction of a Bhutanese medicinal plant, Shug Chher, exhibited inhibition of platelet aggregation induced by platelet activating factor. Bioassay-directed fractionation led to the isolation of four new labdane diterpenoids, 3 alpha, 15-dihydroxy-labda-8(17), 13E-diene (5), 3 alpha-hydroxy-labda-8(17), 13E-dien-15-oic acid (6), 3 alpha-hydroxy-labda-8(17), 12E, 14-trien-19-oic acid (7), and 3 alpha-acetoxyisocupressic acid (8) and four known diterpenoids, manool (1), 3 alpha-hydroxymanool (2), 3 alpha-hydroxy-12, 13E-biformene (3), and isocupressic acid (4). The structures of the new compounds were determined spectroscopically. Compounds 2, 3, and 5 inhibited platelet aggregation.

The chloroform-soluble and n-butyl alcohol-soluble fractions of water extract of Pyrolae Herba inhibited platelet aggregation induced by arachidonic acid and showed a positive inotropic effect. A new naphthoquinone and a new tetralone derivative and known chimaphilin, acetovanillon, and toluhydroquinone were isolated as active constituents. Three new tetralone derivatives were also obtained from an active fraction. The structures of the new compounds were elucidated.

The water extract of Populus sieboldii Miquel (Salicaceae) inhibited arachidonic acid-induced platelet aggregation. Pyrocatechol and salicyl alcohol were isolated as active constituents. Pyrocatechol showed an inhibitory effect on platelet aggregation induced by arachidonic acid with IC100 value of 4 microM, which was 25 times more potent than aspirin.

A trial application of a recent two-dimensional nuclear magnetic resonance experiment to the polypeptide antibiotic siomycin A is described. Proton--carbon-13 chemical shift correlation measures the proton and carbon-13 chemical shift for each directly bonded CH group in a molecule, in a single experiment. The resultant map of correlated chemical shifts enables the carbon-13 spectrum to be assigned directly from the known proton shifts, and allows individual proton signals to be identified without problems of overlap. The signal-to-noise ratio available from such techniques should enable their application to aqueous protein solutions using currently available high-field spectrometers.

The peptide antibiotic siomycin-A was transformed into half-esters with dicarboxylic acids with the intention of making siomycin-A soluble in water. Sodium salts of the half-esters were also prepared. Some of the salts showed antibacterial activities comparable to siomycin-A against Gram-positive bacteria in vitro and exhibited better therapeutic effects in infected mice than siomycin-A. The chemical structures of siomycin-A hemiadipate-II and -III were elucidated by comparing their 13C and 1H NMR spectra with those of siomycin-A. Their physicochemical properties are described.