Factors associated with functional recovery and home discharge in stroke patients admitted to a convalescent rehabilitation ward

Aims: This study aimed to determine the predictive factors for functional recovery and home discharge in stroke patients receiving in-hospital rehabilitation. Methods: This study included a consecutive series of 174 stroke patients (average age 73.0 +/- 10.8) admitted to the convalescent rehabilitation ward at Azumino Red Cross Hospital in Japan after acute rehabilitation. The main outcome measures were functional recovery (functional independence measure [FIM] at discharge and Montebello rehabilitation factor score [MRFS]) and home discharge. Results: Total FIM improved from 72.6 +/- 27.6 to 87.7 +/- 29.9 during the hospital stay (P < 0.001). The average MRFS was 0.30 +/- 0.28. Of the 174 patients, 151 were discharged home (87%). Age, stroke type, premorbid independence, motor FIM, and cognitive FIM at admission showed a significant association with FIM at discharge, while age, premorbid independence, motor FIM at admission, and cognitive FIM at admission were statistically significant predictors of MRFS. Female sex, not living with family, premorbid independence, and neglect were negatively associated with home discharge. Conclusions: Premorbid disability and cognitive dysfunction at admission were both negatively associated with functional recovery and home discharge in patients undergoing inpatient stroke rehabilitation.ArticleGERIATRICS & GERONTOLOGY INTERNATIONAL. 12(2):215-222 (2012)journal articl

Recent Topics in the Studies of Laboratory of Nutrition, Tohoku University : Newly Clarified Function of Vitamin K

Vitamin K (VK) is essential for blood coagulation and bone metabolism in mammals as a Gla-protein activating factor, i.e., VK acts as a cofactor in the posttranslational synthesis of γ-carboxyglutamic acid (Gla) from glutamic acid (Glu) residues in the nascent proteins. Menaquinone-4 (MK-4) is one of the VK_2 analogues, and is well known to have bioactivity in the suppression of bone resorption through apoptosis of osteoclast cells, thus MK-4 is now also used clinically as a therapeutic drug for the osteoporosis. Besides of these well-known functions, MK-4 is strongly presumed to have other novel functions because we have gradually recognized that MK-4 accumulates in various tissues of germfree animals fed an MK-4-free diet. Accordingly, we have focused on clarification of the mechanism of MK-4 formation in several tissues, using both in vitro tissue homogenates (bovine, rats, mice, chicken) and in vivo experiments with rats and mice. To elucidate the biological role of MK-4 production, we used germfree rats to eliminate MK-n synthesized by intestinal flora. Our in vivo results indicate that MK-4 is produced in diverse tissues from ingested vitamin K analogues, including vitamin K_1, MK-n (MK-6, MK-7, and MK-10); and VK_3 without enzymatic participation of microorganisms in the intestine. In addition to the liver and bone, VK is found in the brain, heart, testis, kidney, pancreas and salivary glands mainly as menaquinone-4 (MK-4). However, the physiological role of MK-4 in these various organs has not been fully understood yet. In the present study we identified genes of which expression is changed in testis under vitamin K deficient condition using DNA microarray. The genes involved in the biosynthesis pathway of cholesterol and steroid hormone were decreased in vitamin K deficient group. The amount of Cyp11a (P450scc) mRNA, rate-limiting enzyme for testosterone synthesis, was positively correlated with the concentration of MK-4 in testis. Moreover, the concentration of testosterone in plasma and testis was decreased in vitamin K deficient group compared with the control and vitamin K supplemented groups. These results suggests that vitamin K is involved in steroid production in testis through the regulation of Cyplla

Comparison of FGF1 (aFGF) Expression between the Dorsal Motor Nucleus of Vagus and the Hypoglossal Nucleus of Rat

Neurons in the dorsal motor nucleus of the vagus (DMNV) are more severely affected by axonal injury than most other nerves, such as those of the hypoglossal nucleus. However, the mechanism underlying such a response remains unclear. In this study, we compared the expression of fibroblast growth factor 1 (FGF1), a neurotrophic factor, between the DMNV and the hypoglossal nucleus by RT-PCR and immunohistochemical analyses. RT-PCR showed that the level of FGF1 mRNA expression in the DMNV was lower than that in the hypoglossal nucleus (P<0.01). Immunohistochemistry revealed that FGF1 was localized to neurons. FGF1-positive neurons in large numbers were evenly distributed in the hypoglossal nucleus, whereas FGF1-positive neurons were located in the lateral part of the DMNV. Double immunostaining for FGF1 and choline acetyltransferase demonstrated that 22.7% and 78% of cholinergic neurons were positive for FGF1 in the DMNV and hypoglossal nucleus, respectively. A tracing study with cholera toxin B subunit (CTb) demonstrated that cholinergic neurons sending their axons from the DMNV to the superior laryngeal nerve were FGF1-negative. The results suggest that the low expression of FGF1 in the DMNV is due to severe damage of neurons in the DMNV

Prediction of age and brachial-ankle pulse-wave velocity using ultra-wide-field pseudo-color images by deep learning

This study examined whether age and brachial-ankle pulse-wave velocity (baPWV) can be predicted with ultra-wide-field pseudo-color (UWPC) images using deep learning (DL). We examined 170 UWPC images of both eyes of 85 participants (40 men and 45 women, mean age: 57.5 ± 20.9 years). Three types of images were included (total, central, and peripheral) and analyzed by k-fold cross-validation (k = 5) using Visual Geometry Group-16. After bias was eliminated using the generalized linear mixed model, the standard regression coefficients (SRCs) between actual age and baPWV and predicted age and baPWV from the UWPC images by the neural network were calculated, and the prediction accuracies of the DL model for age and baPWV were examined. The SRC between actual age and predicted age by the neural network was 0.833 for all images, 0.818 for central images, and 0.649 for peripheral images (all P < 0.001) and between the actual baPWV and the predicted baPWV was 0.390 for total images, 0.419 for central images, and 0.312 for peripheral images (all P < 0.001). These results show the potential prediction capability of DL for age and vascular aging and could be useful for disease prevention and early treatment

リポポリサッカライドの外因性投与はコリン欠乏 L-アミノ酸置換食誘発脂肪性肝炎モデルマウスにおいて肝線維化を促進する

Various rodent models have been proposed for basic research; however, the pathogenesis of human nonalcoholic steatohepatitis (NASH) is difficult to closely mimic. Lipopolysaccharide (LPS) has been reported to play a pivotal role in fibrosis development during NASH progression via activation of toll-like receptor 4 (TLR4) signaling. This study aimed to clarify the impact of low-dose LPS challenge on NASH pathological progression and to establish a novel murine NASH model. C57BL/6J mice were fed a choline-deficient l-amino-acid-defined (CDAA) diet to induce NASH, and low-dose LPS (0.5 mg/kg) was intraperitoneally injected thrice a week. CDAA-fed mice showed hepatic CD14 overexpression, and low-dose LPS challenge enhanced TLR4/NF-κB signaling activation in the liver of CDAA-fed mice. LPS challenge potentiated CDAA-diet-mediated insulin resistance, hepatic steatosis with upregulated lipogenic genes, and F4/80-positive macrophage infiltration with increased proinflammatory cytokines. It is noteworthy that LPS administration extensively boosted pericellular fibrosis with the activation of hepatic stellate cells in CDAA-fed mice. Exogenous LPS administration exacerbated pericellular fibrosis in CDAA-mediated steatohepatitis in mice. These findings suggest a key role for LPS/TLR4 signaling in NASH progression, and the authors therefore propose this as a suitable model to mimic human NASH.博士（医学）・甲第738号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

First-order phase transition to a nonmagnetic ground state in nonsymmorphic NbCrP

We report the discovery of a first-order phase transition at around 125 K in NbCrP, which is a nonsymmorphic crystal with the Pnma space group. From the resistivity, magnetic susceptibility, and nuclear magnetic resonance measurements using crystals made by the Sn-flux method, the high-temperature (HT) phase is characterized to be metallic with a non-negligible magnetic anisotropy. The low-temperature (LT) phase is also found to be a nonmagnetic metallic state with a crystal of lower symmetry. In the LT phase, the spin susceptibility is reduced by ∼30% from that in the HT phase, suggesting that the phase transition is triggered by the electronic instability. The possible origin of the phase transition in NbCrP is discussed based on the electronic structure by comparing it with those in other nonsymmorphic compounds, RuP and RuAs

Survey of imaging dose in HDR brachytherapy

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was ≤75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed

ラットを用いた非アルコール生脂肪肝炎におけるアンジオテンシンⅡ受容体拮抗薬とリファキシミン併用薬投与による肝線維化抑制効果の検討

The progression of nonalcoholic steatohepatitis (NASH) is complicated. The multiple parallel-hits theory is advocated, which includes adipocytokines, insulin resistance, endotoxins, and oxidative stress. Pathways involving the gut-liver axis also mediate the progression of NASH. Angiotensin-II receptor blockers (ARB) suppress hepatic fibrosis via the activation of hepatic stellate cells (HSCs). Rifaximin, a nonabsorbable antibacterial agent, is used for the treatment of hepatic encephalopathy and has been recently reported to improve intestinal permeability. We examined the inhibitory effects on and mechanism of hepatic fibrogenesis by combining ARB and rifaximin administration. Fischer 344 rats were fed a choline-deficient/l-amino acid-defined (CDAA) diet for 8 weeks to generate the NASH model. The therapeutic effect of combining an ARB and rifaximin was evaluated along with hepatic fibrogenesis, the lipopolysaccharide-Toll-like receptor 4 (TLR4) regulatory cascade, and intestinal barrier function. ARBs had a potent inhibitory effect on hepatic fibrogenesis by suppressing HSC activation and hepatic expression of transforming growth factor-β and TLR4. Rifaximin reduced intestinal permeability by rescuing zonula occludens-1 (ZO-1) disruption induced by the CDAA diet and reduced portal endotoxin. Rifaximin directly affect to ZO-1 expression on intestinal epithelial cells. The combination of an ARB and rifaximin showed a stronger inhibitory effect compared to that conferred by a single agent. ARBs improve hepatic fibrosis by inhibiting HSCs, whereas rifaximin improves hepatic fibrosis by improving intestinal permeability through improving intestinal tight junction proteins (ZO-1). Therefore, the combination of ARBs and rifaximin may be a promising therapy for NASH fibrosis.博士（医学）・甲第780号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

スルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討

Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.博士（医学）・甲第707号・平成31年3月15日© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0