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Background Clinical evidence to support the use of mechanical thrombectomy (MT) for posterior cerebral artery P2 segment occlusion (P2O) has not been established, and hemiplegia due to P2O improved by MT to our knowledge has not yet been reported. We report 2 cases of P2O with hemiplegia improved by MT. Case Description In case 1, a 68-year-old man was admitted with right hemiplegia and dysesthesia (National Institutes of Health Stroke Scale score 14). Head magnetic resonance imaging showed acute ischemia in the left inferolateral thalamus and posterior limb of the internal capsule. Angiography showed left P2O, which was recanalized after MT. Hemiplegia improved immediately following recanalization, and modified Rankin Scale score at discharge was 0. In case 2, a 69-year-old man was admitted with left hemiplegia and dysesthesia (National Institutes of Health Stroke Scale score 8). Head magnetic resonance imaging showed acute ischemia in the right inferolateral thalamus and posterior limb of the internal capsule. Angiography showed right P2O, which was recanalized after MT, as in case 1. His symptoms resolved completely. Conclusions P2O may cause severe motor deficit. In such cases, MT may contribute to safely improving patients' deficits.

For ligand-protected gold clusters, geometrical differences of gold cores and/or the presence of secondary gold core-ligand interactions influence their unique optical and electronic properties and can, in principle, be detected by spectral changes of gold core vibrations (phonon modes) in ultralow-frequency Raman spectroscopy. We report experimental and theoretical Raman spectra of Au8 clusters protected by phosphine ligands particularly in the "gold cluster fingerprint" region from 50 to 150 cm-1 Raman shift (1.5 to 4.5 terahertz, THz). A characteristic core breathing mode observed at ca. 123 cm-1 was sensitive to differences of core geometries. A new band was found at ca. 150 cm-1, originating from a local strain on a polyhedral gold core caused by weak Au···π interactions. THz Raman spectroscopy can be utilized for metal nanoclusters to visualize core structural changes and Au···π interactions, which cannot be captured by single crystal X-ray analysis.

Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR: congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are caused by activating and inactivating RET mutations, respectively. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (Ret(M919T), Ret(N396K) and Ret(Y792F)) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. Ret(M919T/+) mice displayed MEN2B-related phenotypes, including C-cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in Ret(M919T/-) mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single-allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single-allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity.

Background & Aims: Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of the enteric nervous system (ENS). HSCR potentially involves multiple gene aberrations and displays complex patterns of inheritance. Mutations of the RET gene, encoding the RET receptor tyrosine kinase, play a central role in the pathogenesis of HSCR. Although a wide variety of coding RET mutations have been identified, their pathogenetic significance invivo has remained largely unclear. Methods: We introduced a HSCR-associated RET missense mutation, RET(S811F), into the corresponding region (S812) of the mouse Ret gene. Pathogenetic impact of Ret(S812F) was assessed by histologic and functional analyses of the ENS and by biochemical analyses. Interactions of the Ret(S812F) allele with HSCR susceptibility genes, the RET9 allele and the Ednrb gene, were examined by genetic crossing in mice. Results: RetS812F/+ mice displayed intestinal aganglionosis (incidence, 50%) or hypoganglionosis (50%), impaired differentiation of enteric neurons, defecation deficits, and increased lethality. Biochemical analyses revealed that Ret(S811F) protein was not only kinase-deficient but also abrogated function of wild-type RET in trans. Moreover, the Ret(S812F) allele interacted with other HSCR susceptibility genes and caused intestinal aganglionosis with full penetrance. Conclusions: This study demonstrates that a single RET missense mutation alone induces intestinal aganglionosis via a dominant-negative mechanism. The RetS812F/+ mice model HSCR displays dominant inheritance with incomplete penetrance and serves as a valuable platform for better understanding of the pathogenetic mechanism of HSCR caused by coding RET mutations.

It is well known that alkynes act as π-acids in the formation of complexes with metals. We found unprecedented attractive Au-π interactions in diacetylene-modified [core+exo]-type [Au8 ]4+ clusters. The 4-phenyl-1,3-butadiynyl-modified cluster has unusually short Au-Cα distances in the crystal structure, revealing the presence of attractive interactions between the coordinating C≡C moieties and the neighboring bitetrahedral Au6 core, which is further supported by IR and NMR spectra. Such weak interactions are not found in mono-acetylene-modified clusters, which indicates that they are specific for diacetylenic ligands. The attractive Au-π interactions are likely associated with the low energy of the π* orbital in the diacetylenic moieties, into which the valence electrons of the gold core may be back donated. The [Au8 ]4+ clusters show clear red-shifts of >10 nm with respect to the corresponding mono-acetylenic clusters in UV/Vis absorption bands, which indicates substantial electronic perturbation effects of the Au-π interactions.

For ligand-protected gold clusters, geometrical differences of gold cores and/or the presence of secondary gold core-ligand interactions influence their unique optical and electronic properties and can, in principle, be detected by spectral changes of gold core vibrations (phonon modes) in ultralow-frequency Raman spectroscopy. We report experimental and theoretical Raman spectra of Au

We report a case of thrombectomy beyond one day of onset of right middle cerebral artery occlusion. An 82-year-old woman who presented with difficulty in body movements was transferred to our hospital. After admission, left-sided weakness and dysarthria worsened with an National Institutes of Health Stroke Scale of 9. The initial MRI DWI on admission revealed multiple hyper intense signals in the right cerebral hemisphere and MR angiography revealed occlusion of the right internal carotid artery. We performed medical treatment because FLAIR also revealed hyper intense signals in the same lesion as the DWI image, and more than one day had passed since the onset. However, her symptoms worsened and we performed angiography on the next day, and found contrast defects like crab claw at the top of the right internal carotid artery. Even though more than one day had passed since the onset, we assumed that thrombectomy could prevent the worsening of symptoms. The procedure was a success and it resulted in complete reperfusion to the right middle cerebral artery. She showed improvement after the procedure. According to this case, thrombectomy one day from onset could be considered as a treatment option for large vessel occlusion with good collateral flow in the cases resistant to medical treatment.

It is well known that various transition elements can form M···H hydrogen bonds. However, for gold, there has been limited decisive experimental evidence of such attractive interactions. Herein we demonstrate an example of spectroscopically identified hydrogen bonding interaction of C–H units to Au atoms in divalent hexagold clusters ([Au6]2+) decorated by diphosphine ligands. X-ray crystallography reveals substantially short Au–H/Au–C distances to indicate the presence of attractive interactions involving unfunctionalized C–H moieties. Solution 1H and 13C NMR signals of the C–H units appear at considerably downfield regions, indicating the hydrogen-bond character of the interactions. The Au···H interactions are critically involved in the ligand-cluster interactions to affect the stability of the cluster framework. This work demonstrates the uniqueness and potential of partially oxidised Au cluster moieties to participate in non-covalent interaction with various organic functionalities, which would expand the scope of gold clusters., Many transition metals can form hydrogen bonds to organic species, but experimental evidence for Au is still lacking. Here, the authors obtain crystallographic and NMR spectroscopic evidence of hydrogen bonding between C-H groups and Au atoms of gold clusters, suggesting that non-covalent interactions may play a role in gold cluster catalysis.

Background Use of coil embolization for internal carotid artery-posterior communicating artery aneurysms (IC-PC ANs) has been increasing. However, the recurrence rate after embolization is rather high compared to that after surgery. The aim of this study was to evaluate the factors related to recurrence after coil embolization for IC-PC ANs. Methods A total of 69 patients with IC-PC ANs treated with coil embolization between 2013 and 2019 were retrospectively enrolled, and we evaluated whether the aneurysms recurred after embolization. The patients were divided into two groups (no-recurrence group and recurrence group), and the relationships of several patient or aneurysm characteristics and treatment-related information with aneurysm recurrence were examined. Results Twenty patients (29%) developed aneurysm recurrence. There were significant differences in dome size (5.19 mm/6.48 mm, p = 0.01), neck width (3.25 mm/4.23 mm p = 0.009), aneurysm volume (47.5 mm3/120 mm3, p = 0.003), and Pcom diameter (1.11 mm/1.96 mm p = 0.005) between the two groups. Pcom diameter was the independent risk factor for recurrence (odds ratio: 3.52, 95%CI 1.43–8.69, p = 0.006). The cutoff for Pcom diameter as the factor related to recurrence was 1.79 mm, with sensitivity of 60% and specificity of 83.7%. Conclusion In this study, dome size, neck width, aneurysm volume, and Pcom diameter were associated with recurrence after coil embolization for IC-PC ANs. In particular, Pcom diameter could be an independent risk factor for recurrence.

Importance Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. Objective To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. Design, Setting, and Participants Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. Interventions Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). Main Outcomes and Measures The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. Results Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, −11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞];P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, –0.8% [95% CI, –9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43];P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, –16.8% [95% CI, –32.1% to –1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88];P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, –1.8% [95% CI, –9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24];P = .78). Conclusions and Relevance Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. Trial Registration umin.ac.jp/ctr Identifier:UMIN000021488

Recent advances in the crystal structure determination of ligand-protected metal clusters have revealed that their electronic structures and optical features are essentially governed by the nuclearity and geometries of the inorganic frameworks. In this Perspective, we point out the definite effects of the exterior ligand moieties on the properties of small gold clusters. On the basis of systematic experimental studies on the optical properties of Au8 and Au13 clusters with various anionic ligands, it was shown that not only the “through-bond” electronic effects of coordinating atoms but also the nonbonding interaction with neighboring heteroatoms and the electronic coupling with π-systems cause substantial perturbations. We also suggest that the steric rigidity of the ligand environments affects their photoluminescence efficiencies. These findings imply the feasibility of the facile modulation of the cluster properties through the appropriate choice of ligand modules, which may lead to the evolution of no...

Over recent years, research on the structures and properties of ligand-protected gold cluster molecules has gained significant interest. The crystal structure information accumulated to date has revealed the structural preference to adopt closed polyhedral geometries, but the use of multidentate ligands sometimes leads to the formation of exceptional structures. This Account describes results of our studies on diphosphine-coordinated [core+ exo]-type gold clusters featuring extra gold atoms outside the polyhedral cores, highlighting (1) their distinct optical properties due to the unique electronic structures generated by the exo gold atoms and (2) electronic/attractive ligand-cluster interactions that cause definite perturbation effects on the cluster properties. Subnanometer gold clusters with [core+ exo]-type geometries (nuclearity = 6, 7, 8, and 11) commonly displayed single absorption bands in the visible region, which are distinct in patterns from those of conventional polyhedral-only homologues. Theoretical studies demonstrated that the exo gold atoms are critically involved in the generation of unique electronic structures characterized by the HOMO-LUMO transitions with dominant oscillator strengths, leading to the appearance of the isolated absorption bands. On the basis of the frontier orbital distributions, the HOMO and LUMO were shown to be localized around the polyhedral cores and exo gold atoms, respectively. Therefore, the HOMO-LUMO transitions responsible for the visible absorptions occur in the core → exo direction. The HOMO-LUMO gap energies showed no clear trends with respect to the nuclearity (size), indicating that the individual geometric features of the inorganic framework primarily govern the clusters' electronic structures and properties. Systematic studies using octagold clusters bearing various anionic coligands revealed that electronic or attractive interactions between the gold framework and ligand functionalities, such as π-electron systems and heteroatoms, cause substantial perturbations of the wavelength of the visible absorption band due to the HOMO-LUMO transitions. Especially, significant red shifts were observed as a result of the electronic coupling with specific π-resonance contributors. It was also found that the orientation of aromatic rings around the inorganic framework is a factor that affects the cluster photoluminescence. These findings demonstrate the utility of the ligand moieties surrounding the gold frameworks for fine-tuning of the optical properties. During these studies, unusual but definite attractive interactions between the gold framework and C-H groups of the diphosphine ligand were found in the hexagold clusters. On the basis of careful crystallographic and NMR analyses, these interactions were deemed as a certain kind of M···H hydrogen bonds, which critically affect the maintenance of the cluster framework. Such unique interaction activities are likely due to the valence electrons in the gold framework, which serve as the hydrogen-bond acceptor for the unfunctionalized C-H groups. Overall, these observations imply the uniqueness of the ligand-cluster interface associated with the partially oxidized gold entities, which may expand the scope of ligand-protected clusters toward various applications.

Enteric neural crest-derived cells (ENCCs) migrate from the anterior foregut in a rostrocaudal direction to colonize the entire gastrointestinal tract and to form the enteric nervous system. Genetic approaches have identified many signaling molecules regulating the migration of ENCCs; however, it remains elusive how the activities of the signaling molecules are regulated spatiotemporally during migration. In this study, transgenic mice expressing biosensors based on Förster resonance energy transfer were generated to video the activity changes of the signaling molecules in migrating ENCCs. In an organ culture of embryonic day 11.25 (E11.25) to E13 guts, ENCCs at the rostral wavefront migrated as a cellular chain faster than the following ENCCs that formed a network. The faster-migrating cells at the wavefront exhibited lower protein kinase A (PKA) activity than did the slower-migrating trailing cells. The activities of Rac1 and Cdc42 exhibited an inverse correlation with the PKA activity, and PKA activation decreased the Rac1 activity and migration velocity. PKA activity in ENCCs was correlated positively with the distribution of GDNF and inversely with the distribution of endothelin 3 (ET-3). Accordingly, PKA was activated by GDNF and inhibited by ET-3 in cultured ENCCs. Finally, although the JNK and ERK pathways were previously reported to control the migration of ENCCs, we did not find any correlation of JNK or ERK activity with the migration velocities. These results suggest that external cues regulate the migration of ENCCs by controlling PKA activity, but not ERK or JNK activity, and argue for the importance of live imaging of signaling molecule activities in developing organs.

We report a practical synthesis of PI3K inhibitor GDC-0941. The synthesis was achieved using a convergent approach starting from a thienopyrimidine intermediate through a sequence of formylation and reductive amination followed by Suzuki-Miyaura cross-coupling. Metalation of the thienopyrimidine intermediate involving the intermediacy of triarylmagnesiates allowed formylation under noncryogenic conditions to produce the corresponding aldehyde. We also investigated aminoalkylation via a benzotriazolyl-piperazine substrate as an alternative to the reductive amination route. We evaluated both palladium and nickel catalyzed processes for the borylation and Suzuki-Miyaura cross-coupling. Final deprotection and salt formation afforded the API.

In the recent development of structurally defined ligand-stabilized gold clusters, it has been revealed that not only the inorganic units but also the surrounding organic ligands substantially affect their electronic/optical properties. In this work, a series of core + exo type Au8 clusters decorated by dppp (Ph2P(CH2)3PPh2) and arylthiolate ligands ([Au8(dppp)4(SR)2](2+), 1-5) were synthesized, and their optical properties were studied in order to gain insights into the perturbation effects of the organic ligands. 1-5 showed visible absorption and photoluminescence emission bands at longer wavelengths compared to their chloro- and acetylide-modified analogues, suggesting the contribution of weak non-bonding interactions of the Au framework with the ligand heteroatoms. Upon acid treatment, 2- and 4-pyridinethiolate clusters (R = Py, 2 and 4) showed larger red shifts of the absorption and emission bands than the 3-pyridyl isomer (3), implying the involvement of the resonance structures of the SPy units. On the other hand, all regioisomers (2-4) showed large photoluminescence enhancements upon pyridine protonation. X-ray crystallographic and NMR analyses of 4 and its protonated form (4') showed that the electron-deficient pyridinium rings of 4' form π-stacks with neighbouring phenyl groups of dppp, suggesting that the orientation of the surface aromatics is a plausible factor governing the emission efficiency. These observations provide examples of successful modulation of optical properties of small gold clusters through the electronic and/or steric perturbation by the proximal organic ligands, highlighting the importance of the ligand design in the fine tuning of cluster properties directed for optical chemosensors and luminescent materials.

It is known that soy protein has the hypolipidemic action on blood and liver. We investigated to clarify physiologically effective concentration of soymilk. Male Sprague-Dawley rats aged 7weeks were fed a control die（t AIN-93G, soy protein free）, or a test diet in which 10.78%（corresponding to soy protein 5%）or 21.55%（corresponding to soy protein 10%）of the diet was replaced with soymilk, respectively. The rats were fed the control diet or the test diet for 5weeks. The administration of soymilk significantly suppressed total cholesterol level in plasma and decreased liver lipid and visceral fat. These effects depended on the concentration of administrated soymilk. It was suggested that soymilk improved the lipid metabolism in rat. Moreover, it was found that the administration of amount of soymilk corresponding to more than 10% soy protein was necessary to obtain a significant physiological effect in a short period.

This study examined the effects of fermented soymilk and okara on lipid metabolism in rats. Fermented soymilk and okara was prepared from a mixture of soymilk and okara blended in a ratio of 2 to 1 on dry basis by lactic acid fermentation using Lactobacillus delbrueckii. Male Sprague-Dawley rats were fed a diet based on the AIN-93 diet（ control diet） or two kinds of test diets in which 20% of a control diet was replaced by unfermented soymilk/okara mixture or fermented soymilk/okara for 7 weeks. We investigated changes in plasma and hepatic lipid levels of rats, and the regulation of gene expression in mesenteric adipose tissue and liver by DNA microarray. Groups of test diet significantly reduced plasma cholesterol levels compared with the control diet. In addition, the hepatic triglyceride in rats fed test diets was significantly lower than that of control diet. DNA microarray analysis indicated that the test diet ingestion down-regulated the expression of genes related to lipid metabolism in mesenteric adipose tissue and liver. These results suggested that a mixture of soymilk and okara has the effect improving lipid metabolism. Especially, fermented soymilk and okara seems to promote the restraint of abdominal visceral fat accumulation in comparison with unfermented soymilk and okara. Therefore, fermented soymilk and okara is a functional food showing effect preventing metabolic syndrome.

We examined the effects of lactic acid fermented soymilk, in which part of the soymilk was replaced with okara (soy yogurt), on plasma and hepatic lipid profiles in rats fed a cholesterol-free diet. Additionally, we investigated the effects of soy yogurt on hepatic gene expression in rats using DNA microarray analysis. Male Sprague-Dawley rats aged 5 weeks (n=5/group) were fed a control diet (AIN-93) or a test diet in which 20% of the diet was replaced by soy yogurt for 7 weeks. Soy yogurt consumption did not affect body weight or adipose tissue weight as compared with control diet. In the soy yogurt group, the liver weight and hepatic triglyceride content were significantly lower than the control group, and the level of plasma cholesterol was also lower. Furthermore, DNA microarray analysis indicated that soy yogurt ingestion down-regulated the expression of the SREBP-1 gene and enzymes related to lipogenesis in the rat liver, while expression of beta-oxidation-related genes was up-regulated. These results suggest that soy yogurt is beneficial in preventing hepatic lipid accumulation in rats.

日本型食生活の見直しによる大豆食品特にオカラの有効利用の観点から, オカラ豆乳混合物の乳酸発酵食品 (大豆ヨーグルト) を作製した。大豆ヨーグルトの機能性を検討するために, ラットの脂質代謝に及ぼす効果を調べた。基準飼料に大豆ヨーグルトを添加してラットに摂取させたところ, 基準飼料を摂取した対照群に比較して体重に差違は認められなかったが, 血中コレステロール濃度が低下し, アディポネクチン濃度は低下抑制され, 肝臓コレステロール・中性脂肪濃度が低下を示した。さらに, 大豆ヨーグルト群では胆汁酸の糞中排泄量が高値を示し, 大豆の乳酸発酵効果が認められた。以上の結果から, 大豆ヨーグルトは生活習慣病予防において有効な新規機能性大豆食品であると示唆された。

Background Compared to those found in the vertebrobasilar system, intracranial dissection in the anterior circulation is relatively rare, especially in the anterior cerebral artery (ACA). Moreover, only several cases of ACA dissection that underwent endovascular treatment have been reported. Here we present a rare case of gradually developing ACA dissecting aneurysm causing cerebral infarction, successfully treated by stent-assisted coil embolization. Case description A 36-year-old man was admitted with sudden right hemiparesis. Diffusion-weighted magnetic resonance (MR) imaging showed cerebral infarction in the left ACA territory, and MR angiography showed segmental stenosis at the A2 portion of the left ACA. Three-dimensional digital subtraction angiogram showed segmental dilatation and stenosis at the left A2 portion. We diagnosed ACA dissection causing acute cerebral infarction and treated the patient conservatively. Five months after the onset, the dissecting artery at the left A2 portion formed a gradually dilating aneurysm, suggesting increased risk for aneurysmal rupture. We attempted endovascular treatment entailing coil embolization of an aneurysm while preserving the left A2 with stent assistance. The patient remained neurologically stable 6 months after the procedure. Conclusions Although there are few reported cases of ACA dissection where endovascular treatment was attempted, we consider stent-assisted embolization for gradually developing ACA dissecting aneurysm as an alternative method to prevent bleeding and recurrent infarction.

From October 2011 to September 2012, we collected the specimen from 316 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 357 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 51, Streptococcus pneumoniae 73, Haemophilus influenzae 88, Pseudomonas aeruginosa (non-mucoid) 34, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 21, and Moraxella catarrhalis 33. Of 51 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 31 (60.8%) and 20 (39.2%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA, vancomycin showed the potent activity and inhibited the growth of all the strains at 1 μg/mL. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 μg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 μg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.5 and 1 μg/mL, respectively. In contrast, there were high-resistant strains (MIC:128 μg/mL) for erythromycin (53.4%) and clindamycin (3 5.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 μg/mL or less. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2 μg/mL. Against K. pneumoniae, imipenem had the most potent activity and inhibited the growth of all the strains at 0.125 μg/mL. All the antibacterial agents except ampicillin generally showed a potent activity against M catarrhalis and the MIC90 of them were 2 μg/mL or less. The majority number (52.9%) of the patients with respiratory infection was aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 59.2% and 19.3% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (17.8%), S. pneumoniae (21.6%), and H. influenzae (16.9%). H. influenzae (36.8%) and S. pneumoniae (22.1%) also were frequently isolated from the patients with chronic bronchitis. The bacteria frequently isolated from the patients were S. pneumoniae (23.2%) and H. influenzae (27.3%) before administration of the antibacterial agents. The bacteria frequently isolated from the patients previously treated with cephems were H. influenzae and P. aeruginosa, and the isolation frequencies were 38.5% and 23.1%, respectively. The bacteria frequently isolated from the patients previously treated with macrolides were H. influenzae, the isolation frequencies were 30.0%.

Bacteria isolated from surgical infections during the period from April 2010 to March 2011 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 631 strains including 25 strains of Candida spp. were isolated from 170 (81.7%) of 208 patients with surgical infections. Four hundred and twenty two strains were isolated from primary infections, and 184 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus avium was highest, followed by Streptococcus spp. such as Streptococcus anginosus and Staphylococcus spp. such as Staphylococcus aureus, in this order, from primary infections, while Enterococcus spp. such as E. faecalis and E. faecium was highest, followed by Staphylococcus spp. such as S. aureus from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Pseudomonas aeruginosa in this order, and from surgical site infection, E. coli and R aeruginosa were most predominantly isolated, followed by E. cloacae and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rates of Parvimonas micra, Eggerthella lenta, Streptococcus constellatus, Gemella morbillorum, and Collinsella aerofaciens were the highest from primary infections, and the isolation rate from surgical site infection was generally low. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by, Bacteroides fragilis and Bacteroides ovatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides thetaiotaomnicron, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant S. aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed.

Soybean is widely used in Japanese dietary pattern. Okara is a by-product generated mainly during processing of soybean. A great deal of okara has been treated as industrial waste. A lot of soy proteins which are functional components are included in okara. We have proposed a beneficial use for okara. Yoghurt-like food used in this experiment was prepared from a mixture of okara and soymilk by lactic acid fermentation. We investigated nutritional and food characteristics of this yoghurt-like food and obtained following results. Soy proteins in okara and soymilk were scarcely digested during the fermentation. Some soy proteins have been known to exhibit cholesterol-lowering effect. In the yoghurt-like food lactic acid occurred predominantly among several organic acids detected by HPLC. An improvement effect on enteric environment was expected because stachyose could not be degraded by lactic acid fermentation and it would be used by other microorganisms in intestine. The difference of isoflavone content between the unfermented food and yoghurt-like food was not observed. Soy isoflavones remained without degradation during lactic acid fermentation. These results suggested that the intake of yoghurt-like soy food would improve serum cholesterol concentration and intestinal environment.

Yogurt-like food (Soy-Yogurt) was prepared by lactic fermentation of okara and soybean milk which suppress the increase of blood lipid level. To investigate the effect of Soy-Yogurt on the lipid metabolism in rat, male Sprague-Dawley rats were fed a high-cholesterol diet for 8 weeks. A control group was fed a diet containing 1% cholesterol, while the other two groups were fed the diets which were replaced with freeze-dried Soy-Yogurt either 10% or 20%, respectively. The increases of body weight and total cholesterol level in plasma of 20% Soy-Yogurt group were significantly suppressed compared to those of the control group, respectively. The twenty percentage Soy-Yogurt group maintained a high level of plasma adiponectin. The levels of hepatic total lipid, cholesterol and triglyceride were significantly decreased with the increase of Soy-Yogurt content in the feed. These results suggest that the ingestion of Soy-Yogurt improves the lipid metabolism in rats fed a high-cholesterol diet.

In running of artificial tracks, the optimum cushioning characteristics of running shoes depend on the hardness of track materials. In this study, the cushioning characteristics of running shoes were investigated by conducting mechanical tests and by analyzing runners' sensory evaluations of shoes used on artificial tracks. These tests and evaluations provide information on how the optimum sole cushioning of running shoes was affected by the hardness of artificial tracks and how the mechanical properties correlated with the sensory evaluations of distance runners. Drop weight impact tests were carried out on 4 types of running shoe soles which had 4 different hardness of EVA, and with 4 types of artificial tracks which had 4 different materials and constructions. Running shoes and artificial tracks were evaluated by energy absorption and average Young's modulus which were typical parameters given by the force and deformation relationships derived from mechanical tests. At the same time, evaluations of shoes were carried out by 4 distance runners who wore 4 different shoes on 4 different stadiums. Shoes' evaluations were based on whole evaluation, cushioning, and stability. Data acquisitions of sensory evaluations and after processing were conducted based on Scheffe's method. The results of this study are as follows; (1) Scheffe's method is effective for assessing runners' sensory evaluations of shoes, (2) Runners' sensory evaluations seem to be based on shoe sole hardness, that is, average Young's modulus, (3) In the case of running on a hard surface, runners' favorite average Young's modulus is about 70kN/m shoe sole, and (4) In the case of deformable surfaces, runners' favorite shoe sole hardness varies slightly from 70kN/m, depending on the materials and the constructions of artificial tracks.

An enantioselective total synthesis of AI-77-B (1), a gastroprotective substance isolated from a culture broth of Bacillus pumilus AI-77, was performed in high overall yield. In this synthesis, the dihydroisocoumarin part 14 and the dihydroxyamino acid part 20 were both assembled from d-ribose as the common chiral source. For the construction of 14 a bromobenzofuran derivative was used as a novel salicylic acid synthon. Finally, DEPC-mediated condensation of 14 and 20 yielded AI-77-B (1).

A variety of cyclic and acyclic ethers are efficiently reacted with acyl chlorides or acyl bromides to afford the ether-cleaved compounds of ω-chloro-or ω-bromoesters under high pressure conditions. The reactivity of ethers is found to be roughly depend on the basicity of the ether oxygen atom.

High-pressure reaction of N -Boc-lactams with amines provides an efficient entry to ω- N -Boc-amino-carboxamide derivatives.

The hydroxyamino acid moiety of AI-77-B, pyrrolidin-2-one derivative, has been prepared from D-ribose in an optically pure form via stereoselective alkylation of N-acylpyrrolidinium ion intermediates as the key step

Bacteria isolated from surgical infections during the period from April 2011 to March 2012 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 785 strains including 31 strains of Candida spp. were isolated from 204 (78.8%) of 259 patients with surgical infections. Five hundred and twenty three strains were isolated from primary infections, and 231 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp. and Staphylococcus spp., in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa, K. pneumoniae, and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Collinsella aerofaciens, Lactobacillus acidophilus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated, followed by P micra and L. acidophilus, in this order. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroidesfragilis was the highest from primary infections, followed by Bilophila wadsworthia, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides vulgatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides caccae, B. thetaiotaomicron, Bacteroides ovatus and B. wadsworthia, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant Staphylococcus aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed. We should carefully follow up B. wadsworthia which was resistant to various antimicrobial agents, and also Bacteroides spp. which was resistant to many β-lactams.