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[Purpose] The characteristics of neck and shoulder pain (NSP) in different age populations have not been sufficiently examined. Therefore, the purpose of this study was to compare and verify the cervicothoracic spinal alignment and neck flexor muscle endurance of young and older adult females with and without NSP. [Participants and Methods] We assessed 72 female participants (39 young participants, 33 elderly participants, 43 NSP, 29 non-NSP) aged 18-82 years who were recruited for this study. Cervicothoracic spinal alignment measurements were obtained with forward head alignment (FHA) along with the upper thoracic angle. The neck flexor endurance test was performed. [Results] There were no significant age-by-group interactions for any of the assessment variables. However, the upper thoracic angle and neck flexor muscle endurance showed significant effects in the groups. Age also had significant effects on FHA and upper thoracic angle. [Conclusion] These results suggested that the neck flexor muscle endurance was more appropriate as an evaluation tool for older adult females with NSP. It was also suggested that the cervical flexor muscle endurance and upper thoracic angle were more appropriate as evaluation tools for young adult females with NSP.

Recent clinical practice guidelines for chronic pain indicate, with a high evidence level, that the combination of exercise and cognitive behavioral therapy (CBT) is effective. The purpose of this study was to evaluate the effectiveness of an exercise facilitation method in combination with CBT using the “Ikiiki Rehabilitation Notebook” for patients with intractable chronic pain. “Ikiiki” means active in Japanese. A total of 22 cases with chronic low back (n = 13), lower extremity (n = 8), or neck (n = 1) pain were treated using this notebook. Two cases dropped out, leaving 22 cases. Each case was evaluated in terms of the numerical rating scale (NRS) of the pain, activities of daily living (ADL), pain catastrophizing scale (PCS), and quality of life (QOL) at pretreatment and post-treatment. The endpoint of the method was to achieve the long-term goals set by the patients. The mean treatment period was 11.2 months. The outcomes were as follows: improvement of presenteeism: nine cases; enhanced participation in hobbies: seven cases; improved school attendance: two cases; return to work: one case; improvement of self-care and/or self-efficacy: three cases. The NRS, ADL, PCS, and QOL were significantly improved after the treatment. This method is possibly valuable for educating patients about the cause and treatment of chronic pain and actively facilitating exercise and social participation. Further studies are needed to investigate the effectiveness of using this notebook for the patient with intractable chronic pain.

Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjögren-Larsson syndrome (SLS) is one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. In this study, we found that Aldh3a2 is expressed in oligodendrocytes and neurons in the mouse brain, and neurons of Aldh3a2 knockout (KO) mice exhibited impaired metabolism of the long-chain base, a component of sphingolipids. Aldh3a2 KO mice showed several abnormalities corresponding to SLS symptoms in behavioral tests, including increased paw slips on a balance beam and light-induced anxiety. In their brain tissue, 2-hydroxygalactosylceramide, an important lipid for myelin function and maintenance, was reduced by the inactivation of fatty acid 2-hydroxylase. Our findings provide important new insights into the molecular mechanisms responsible for neural pathogenesis caused by lipid metabolism abnormalities.-Kanetake, T., Sassa, T., Nojiri, K., Sawai, M., Hattori, S., Miyakawa, T., Kitamura, T., Kihara, A. Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.

Although very few studies have addressed the molecular and cellular mechanisms underlying the development of biliary tract cancer (BTC), several lines of evidence suggest a role for the erbB receptor family. Overexpression and activation of erbB2 has been reported in a significant percentage of human BTC. Further, we previously reported that overexpression of erbB2 basal epithelial cells of the biliary tract (BK5.erbB2 mouse) led to the development of BTC. However, the mechanisms by which erbB2 overexpression led to the spontaneous development of tumors specifically in the biliary tract are not completely understood. The goals of the current study were to (1) determine whether a cooperative relationship between bile acid exposure and erbB2 activation exists during biliary tract carcinogenesis and (2) to characterize the mechanism(s) underlying bile acid-mediated biliary tract carcinogenesis in cells with activated erbB2. In this study, we demonstrated that the secondary conjugated bile acid, taurochenodeoxycholic acid (TCDC), increased proliferation of primary cultured gallbladder epithelial cells from BK5.erbB2 mice and human BTC cells. TCDC treatment activated EGFR/erbB2 and downstream signaling molecules in both primary cultured cells and human BTC cells. TCDC also increased the expression of epidermal growth factor receptor (EGFR) ligands and TACE activity in human BTC cells. Inhibition of src activation led to attenuation of bile-induced upregulation of TACE activity as well as signaling through the EGFR/erbB2, suggesting that during the development of BTC erbB2 overexpression/activation accelerates the bile acid-induced signaling cascade: bile acid src TACE EGFR/erbB2 downstream signaling. We also provide direct evidence that bile acids possess tumor promoting capacity in epithelial cells overexpressing erbB2 using the two-stage skin carcinogenesis model. Collectively these findings suggest cooperative roles for bile acid and erbB2 activation in epithelial cell proliferation; bile acid appears to accelerate erbB2-induced pro-tumorigenic activities in the biliary tract and skin. © 2013 Wiley Periodicals, Inc.

The erbB family of receptor tyrosine kinases are known to play important roles in normal epithelial development and epithelial neoplasia. Considerable evidence also suggests that signaling through the epidermal growth factor receptor (EGFR) plays an important role in multistage skin carcinogenesis in mice; however, less is known about the role of erbB2. In this study, to further examine the role of both erbB2 and EGFR in epithelial carcinogenesis, we examined the effect of a dual erbB2/EGFR tyrosine kinase inhibitor, GW2974, given in the diet on skin tumor promotion during two-stage carcinogenesis in wild-type and BK5.erbB2 mice. In BK5.erbB2 mice, erbB2 is overexpressed in the basal layer of epidermis and leads to heightened sensitivity to skin tumor development. GW2974 effectively inhibited skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in wild-type and BK5.erbB2 mice, although a more marked effect was seen in BK5.erbB2 mice. In addition, this inhibitory effect was reversible when GW2974 treatment was withdrawn. GW2974 inhibited 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation, which correlated with reduced activation of both the EGFR and erbB2. These results support the hypothesis that both the EGFR and erbB2 play an important role in the development of skin tumors during two-stage skin carcinogenesis, especially during the tumor promotion stage. Furthermore, the marked sensitivity of BK5.erbB2 mice to the inhibitory effects of GW2974 during tumor promotion suggest greater efficacy for this compound when erbB2 is overexpressed or amplified as an early event in the carcinogenic process. Cancer Prev Res; 3(8); 940–52. ©2010 AACR.

This paper proposes a robotic walker system with standing, walking and seating assistance function. Our system focuses on domestic use for aged person who needs nursing in their daily life. Our key ideas are two topics. The first topic is combination of standing assistance function and walking assistance function. In previous works, many assistance devices are specialized in only “standing-up operation” or “walking operation”. However, in their daily life, elderly people need standing, walking and seating assistance continuously by the same device. Therefore, our developing assistance system can support both operations by a small sized mechanism which is easy to use in the home. The second topic is a seating position adjustment assistance. From questionnaires of nursing specialists, a seating position adjustment requires the elderly people to walk backward and it is difficult operation for them. Furthermore, in many cases, a failure of this operation causes a fracture which has high risk to fall into bedridden life. Thus, our developing system can assist the aged users to adjust the seating position safety. The performance of our proposed system is verified by experiments using our prototype.

OBJECTIVE—Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance RESULTS—Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 ± 62 vs. 121 ± 55 pg/ml, P < 0.001; urinary IL-18 97 ± 159 vs. 47 ± 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA1c (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary β-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042). CONCLUSIONS—Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.

Background Annual urinary screening is conducted at municipal kindergartens, elementary schools, and junior high schools in Ikeda City, Osaka, Japan (Ikeda City School System), and the results are reviewed by a general physician, but standards for when to recommend specialist referral have not been clear. Methods In all children attending the Ikeda City School System in 2012, dipstick urinalysis of a first-morning urine specimen was recommended once or twice, and if a second urinalysis showed proteinuria (≥1+), the urinary protein/creatinine ratio was measured. If this showed ≥0.2 g/g of creatinine (g/gCr), it was recommended that the child be evaluated by a specialist at Ikeda City Hospital. Results Urinary screening was performed in about 20% (388) of kindergarten, about 90% (5363) of elementary school, and about 86% (2523) of junior high school children living in Ikeda City. Urine samples were obtained from 387, 5349, and 2476 children, respectively. The urinary protein/creatinine ratio was ≥0.2 g/gCr in 13 children, including 1 elementary and 12 junior high children. In these 13 children, chronic nephritic syndrome (CNS) was suspected in 6 junior high school children, and of these, this was a new finding in 5, and renal biopsy was indicated in 3. In Ikeda City, the prevalence of CNS in elementary school children was

The incidence of esophageal adenocarcinoma (EAC) is rising rapidly throughout the Western world, and is associated with gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE). BE is intestinal metaplasia of squamous esophageal epithelium, important clinically due to the fact that it increases an individual's chance of progression to EAC 30 to 125-fold higher than people without BE. Despite its clinical importance, the molecular pathogenesis of BE is poorly understood. One limitation in the study of BE pathogenesis has been the lack of suitable experimental models. There is a critical need to develop good preclinical models of BE. ErbB2 was reported to be amplified and overexpressed in BE, EAC, and esophageal squamous cell carcinoma (ESCC). However, the role of erbB2 in the development and progression of esophageal cancer is still unknown. In this study, we utilized BK5.erbB2 mice, in which erbB2 is overexpressed in epithelial cells under the control of the bovine keratin 5 promoter to determine whether the interaction between erbB2 and bile acids is important in the etiology of esophageal cancers. BK5.erbB2 mice (2 months of age, n=8) and age matched wild type mice (n=10) were treated with porcine bile extract (10mg/mouse in 200μL water), taurochenodeoxycholate (TCDC) (0.1μmol/mouse in 200μL water), or water control, 3 times weekly for 14 weeks by gavage. In the BK5.erbB2 mice, exophytic tumors in the forestomach, which has the same histological structure of esophagus, were observed in 20%, 33%, and 0% of mice treated with bile extract, TCDC, and water control, respectively. No tumors were observed in wild type mice. All tumors observed in BK5.erbB2 mice were diagnosed as SCC. Western blotting analysis demonstrated that the bile acid treatment increased the levels of p-EGFR, p-MAPK, and p-Akt in the forestomachs of the BK5.erbB2 mice. Furthermore, CDX2 (a marker of BE) was significantly expressed in BK5.erbB2 mice treated with bile extract or TCDC. No development of intestinal metaplasia in forestomach was found. We further investigated using a surgically manipulated reflux model. Eleven 7 week-old BK5.erbB2 and 5 wild type mice were given an esophagogastroduodenostomy. Mice were sacrificed at post-operative week 8, and examined histologically. Hyperkeratosis and intestinal metaplasia were observed at the anastomosis sites in both BK5.erbB2 and wild type mice. These histological changes were more prominent in BK5.erbB2 mice. Interestingly, dysplastic lesions were observed only in BK5.erbB2 mice. These results indicate that more persistent exposure of bile via surgery induce the development of not only SCC, but also precancerous lesions of adenocarcinoma in the esophagus/forestomach of BK5.erbB2 mice. The interaction between erbB2 and bile acids is important in esophageal tumor formation and intestinal metaplasia. A surgical model using BK5.erbB2 mice could possibly be a promising model for the study of the development of EAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1331. doi:1538-7445.AM2012-1331

Esophageal cancer is considered to be one of the most lethal cancers, with a 5-year survival rate of approximately 23% to 50% for patients, even after complete resection with lymph node dissection. There are two common forms of esophageal cancer: squamous cell carcinomas (ESCCs) and adenocarcinomas (EACs). It has been shown that the initial step in the development of EACs is the transformation of normal stratified squamous epithelium in the lower esophagus to metaplastic specialized columnar epithelium (SCE), a pathological condition caused by chronic gastroesophageal reflux of gastric acid and bile known as Barrett's esophagus (BE), and it is possible that this condition also leads to the development of ESCCs as well. Although it has been reported that erbB2 is strongly expressed in SCE, EACs, and ESCCs, the role of erbB2 in the development and progression of esophageal cancer is still unknown. Furthermore, the contribution of bile acids in the etiology of esophageal cancer has not been explored. In this study, to determine whether interaction between erbB2 and bile acids is important in the etiology of esophageal cancers, we utilized BK5.erbB2 mice, in which erbB2 is overexpressed in epithelial cells under the control of the bovine keratin 5 promoter. Eight two-month-old homozygous BK5.erbB2 mice and 8 wild type mice were initiated with N-nitrosomethylbenzylamine (NMBA, 50μg/mouse in 200μL water, twice weekly for 3 consecutive weeks). Mice were then treated with porcine bile extract (10mg/mouse in 200μL water, 3 times weekly for 4 weeks) by gavage. Mice were sacrificed 24 hours after the last treatment and histopathological analyses in the esophagus, forestomach, squamocolumnar junction within the glandular stomach, and other tissues were performed. In wild type mice, only 20% of mice treated with NMBA/bile extract developed small papillomas in the forestomach and squamocolumnar junction at the stomach. In BK5.erbB2 mice, 50% of mice treated with bile extract alone developed significant hyperplasia, 63% of mice treated with NMBA alone developed papillomas, and 100% of mice treated with NMBA/bile extract developed large SCCs in these areas. BK5.erbB2 mice treated with bile extract also showed significantly elevated levels of cell proliferation as determined by 5-bromo-2′-deoxyuridine incorporation in esophagus and forestomach compared to wild type mice. These results indicate that bile acids may play an important role in the development of stomach/esophageal tumors where erbB2 is overexpressed and/or activated. In this regard, bile acids may promote the development of these tumors. Furthermore, these studies demonstrate the utility of the BK5.erbB2 mouse as a novel model for human stomach and esophageal cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4176.

塩酸ミノサイクリン (MINO, 日本レダリー, 東京) を用いて歯周炎の局所治療法を確立するための研究を行なってきた。本研究は, MINOを2% (力価) に含有する軟膏製剤 (LS-007) を臨床的に用い, その有効性, 安全性ならびに有用性をもとに用法を検討したものである。4mm以上のポケットを有する辺縁性歯周炎患者45名の119歯を被験歯とし, LS-007とそのプラセボ, および市販のミノマイシン錠 (日本レダリー) を用い, 微生物学的および臨床的に用法を検討した。その結果, LS-007の局所投与は歯周病治療において, 臨床的有効性, 安全性および有用性があると結論した。

The use of antiplatelet therapy (APT) and/or anticoagulant therapy (ACT) continues to increase due to the aging population. Because the management of patients with acute cholecystitis receiving APT/ACTis still unclear, surgeons are sometimes faced with the difficult decision to delay surgery. We aimed to analyze characteristics and surgical risks of patients who underwent emergency cholecystectomy for acute cholecystitis without discontinuing APT. We conducted a retrospective review of 113 patients between 2006 and 2014. Treatment outcomes among 13 patients who underwent cholecystectomy without discontinuing APT (the cAPT group), 11 patients who discontinued APT and ACT (the D group), and 89 patients who did not receive preoperative APT and/or ACT (the No APT group) were compared. There were no significant differences in intraoperative blood loss, conversion to open surgery, and bleeding-related complications. However, the incidence of intraoperative blood transfusion was higher in the cAPT group (P = 0.04). They presented with severe local inflammation; thus, it was difficult to stop bleeding from the gallbladder bed. Hemostatic tools for liver surgery were used to control bleeding. Emergency cholecystectomy was tolerable for patients with acute cholecystitis while continuing APT. However, in case of severe local inflammation, there is a greater risk for massive hemorrhage.