Anti-Inflammatory Actions of Expectorants in a Rat Carrageenan-Induced Footpad Edema Model.

S-Carboxymethyl-L-cysteine (SCMS) exhibits sputum-regulating and anti-inflammatory actions. Previous studies reported the anti-inflammatory effects of SCMS on chronic inflammatory diseases, but no study has examined these effects on acute inflammatory diseases. In this study, we investigated the anti-inflammatory effects of SCMS in a rat carrageenan-induced footpad edema model, which is routinely used as an acute inflammation model. Expectorants were administered to rats with footpad edema induced by subcutaneously administering 1%λ-carrageenan to the footpad of the left posterior limb, and the dose dependency of the anti-inflammatory effects was evaluated. As a result, even when the dose of SCMS was increased to 400 mg/kg, there were no inhibitory effects on edema. Furthermore, we examined the inhibitory effects of other expectorants (ambroxol hydrochloride, N-acetyl-L-cysteine, L-cysteine ethylester hydrochloride, and L-cysteine methylester hydrochloride), which were reported to exhibit anti-inflammatory effects on chronic inflammation, on edema. However, none of these expectorants inhibited edema.

Change in sense of food safety associated with social connectedness and information sources-A 10-year longitudinal survey before and after the Fukushima nuclear power plant accident.

OBJECTIVES: This study analyzes the change in the sense of food safety over time, from 2 years before to 8 years after the Fukushima accident in 2011, and its association with social connectedness using cohort data, taking into account regional differences in Fukushima Prefecture. STUDY DESIGN: Repeated cross-sectional data from Fukushima Prefectural Government from 2009 to 2018 were used. METHODS: We randomly selected 1300 people every fiscal year (FY). The survey gathered data on age, gender, occupation, residential region, and the explanatory variables 'sense of social connectedness' and 'recovery-related information source' (information source). The prefecture was divided into three regions for the survey-Hamadori region, where the nuclear power plant is located, Nakadori region, where the air dose rate after the earthquake was high, and in Aizu, far from the nuclear power station but has suffered from harmful rumors. RESULTS: Focusing on FY 2014, when the sense of safety first showed recovery, we performed a binominal logistic regression analysis with 'sense of safety' as the outcome and 'sense of social connectedness' and 'information source' as the explanatory variables. The sense of safety significantly decreased in all regions in 2011 relative to earlier years. The sense of food safety decreased markedly in Hamadori and Nakadori but started to improve 3 years after the earthquake and reached the pre-earthquake level in 2018. The effect sizes were larger in the Hamadori region and in Nakadori than in Aizu. In FY 2014, multivariate analysis found that a sense of food safety was significantly positively associated with a sense of social connectedness, whereas the use of information from newspapers and TV and word of mouth was negatively associated. CONCLUSION: Although the recovery of a sense of food safety may take some time, a focus on social connectedness during recovery and scrutiny of information sources may facilitate recovery. Health communication has an important role when the provider sends information intelligibly and the recipient can distinguish good news from bad and link it to self-determination. It is necessary to improve literacy.

Cultural identity, leadership and well-being: how indigenous storytelling contributed to well-being in a New Zealand provincial rugby team.

OBJECTIVES: The purpose of the article was to explore the application and interpretation of indigenous stories introduced in 2015-2017 in relation to the identity and leadership (well-being elements) of players and coaches of a men's provincial rugby team in Aotearoa/New Zealand (NZ). STUDY DESIGN: The study utilised a Kaupapa Maori case study approach and indigenous forms of storytelling (purakau, whakatauki) to encourage participants to share their narratives and experiences of how the inclusion of Maori knowledge in a team context influenced their sense of identity and leadership and thus well-being on and off the field. METHODS: Semi-structured, one-on-one, interviews alongside focus group discussions generated the data (narratives) collected. Data were thematically analysed, utilising aspects of an indigenous model of Health Promotion known as Te Pae Mahutonga. Specifically, the cultural identity affirmation (Mauri Ora) and leadership (Nga Manukura) elements were illustrated as these were applicable to high performance sport contexts. RESULTS: Analysis revealed that the team narrative, values and expectations were enhanced by embracing Maori stories (purakau) and symbols. In particular, this enhanced the cultural identity, sense of belonging, leadership and well-being of a number of team members on and off-field. Neither the players nor coaches disclosed any negative impacts to their well-being from incorporating indigenous storytelling (purakau, whakatauki) into their team building practices and culture. CONCLUSIONS: Sport-related research and practices that are informed by indigenous knowledge and values can benefit the well-being of indigenous people (in this case Maori), collectives (rugby team) and individuals (researchers, players and coaches). Further research exploring how indigenous knowledge is integrated into sport-related contexts is needed to understand whether the well-being of a wider range of teams and individuals (women, non-indigenous) may benefit from the inclusion of indigenous knowledge, values and practices.

Sagittal alignment and mobility of the thoracolumbar spine are associated with radiographic progression of secondary hip osteoarthritis.

OBJECTIVE: To identify predictors of radiographic progression of hip osteoarthritis (OA) over 12 months among functional hip impairments and spinal alignment and mobility. DESIGN: Fifty female patients with secondary hip OA, excluding those with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA over 12 months (>0.5 mm in JSW) as dependent variable, logistic regression analyses were performed to identify predictors for hip OA progression among functional impairments of the hip and spine with and without adjustment for age, body mass index (BMI), and minimum JSW at baseline. The independent variables were hip pain, Harris hip score (HHS), hip morphological parameters, hip passive range of motion (ROM) and muscle strength, and alignment and mobility of the thoracolumbar spine at baseline. RESULTS: Twenty-one (42.0%) patients demonstrated radiographic progression of hip OA. Multivariable logistic regression analysis showed that larger anterior inclination of the spine in standing position (adjusted OR [95% CI], 1.37 [1.04-1.80]; P = 0.028) and less thoracolumbar spine mobility (adjusted OR [95% CI], 0.96 [0.92-0.99]; P = 0.037) at baseline were statistically significantly associated with radiographic progression of hip OA, even after adjustment for age, BMI, and minimum JSW. CONCLUSIONS: The findings suggest that spinal alignment and mobility should be considered when assessing risk and designing preventive intervention for radiographic progression of secondary hip OA.

Daily cumulative hip moment is associated with radiographic progression of secondary hip osteoarthritis.

OBJECTIVE: To investigate whether higher daily cumulative hip moment at baseline is associated with subsequent radiographic progression of hip osteoarthritis (OA) over 12 months. DESIGN: Fifty patients with secondary hip OA, excluding patients with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA (>0.5 mm/year in JSW) as dependent variable (yes/no), univariable and multivariable logistic regression analyses were performed to assess the association between load-related parameters during gait (i.e., peak hip moment, hip moment impulse, and daily cumulative hip moment [product of hip moment impulse and mean steps/day]) and hip OA progression with and without adjustment for age, body weight, and minimum JSW. RESULTS: Of the 50 patients (47.4 ± 10.7 years old), 21 (42.0%) were classified into the progression group. The higher daily cumulative hip moment in the frontal plane at baseline was statistically significantly associated with radiographic progression of hip OA (adjusted odds ratio (OR) [95% confidence interval (CI)], 1.34 [1.06-1.70]; P = 0.013). The higher daily cumulative hip moment in the sagittal plane was also approaching significance in its association with hip OA progression (adjusted OR, 1.80 [0.99-3.26]; P = 0.052). CONCLUSIONS: In the female patients with secondary hip OA, higher daily cumulative hip moment, particularly in the frontal plane, was a predictor of radiographic progression of hip OA over 12 months. Reduction in daily cumulative hip moment by modification in gait and physical activity may potentially slow hip OA progression.

A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components.

Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration.

Mutation of DNASE1 in people with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extremely high immunoglobulin G titer against nucleosomal antigens. These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.

Association between Reduction of Muscle Mass and Faster Declines in Global Cognition among Older People: A 4-Year Prospective Cohort Study.

OBJECTIVES: A few studies reported that both decrease and increase in body mass index (BMI) were associated with the development of dementia in later life. However, it is unclear what changes in body composition are associated with cognitive decline. This study investigated the longitudinal influences of changes in body composition on cognitive function among community-dwelling adults. DESIGN, SETTING AND PARTICIPANTS: This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in National Institute for Longevity Sciences - Longitudinal Study of Aging. MEASUREMENTS: Cognitive function was assessed using the MMSE. Body composition was measured by a dual-energy X-ray absorptiometry system. Then, BMI, fat mass index (FMI), fat-free mass index (FFMI), and muscle mass index (MMI) were calculated. The changes in body composition over 6 years (second wave to fifth wave) were calculated, and three groups were created: decreased group, decrease of >5%; stable group, change within 5%, and increased group, increase of >5%. In statistical analysis, a linear mixed model was applied by sex to investigate the influences of body composition changes on cognitive function over 4 years (fifth wave to seventh wave). RESULTS: This study analyzed 515 participants (mean age, 67.05 years; 53.4% men). Men with decreased group in FFMI and MMI exhibited faster declines in MMSE scores than those with stable group (ß [95% CI]: FFMI, -0.293 [-0.719 to -0.020]; MMI, -0.472 [-0.884 to -0.059]). In women, there was no significant association between body composition changes and cognitive functions. CONCLUSIONS: Decrease in fat-free mass and muscle mass is associated with faster cognitive declines in men. These results suggest the importance of continuous monitoring of muscle mass to prevent cognitive decline in later life.

A model to predict the frequency of integration of fitness-related QTLs from cultivated to wild soybean.

With the proliferation of genetically modified (GM) products and the almost exponential growth of land use for GM crops, there is a growing need to develop quantitative approaches to estimating the risk of escape of transgenes into wild populations of crop relatives by natural hybridization. We assessed the risk of transgene escape by constructing a population genetic model based on information on fitness-related QTLs obtained from an F (2) population of wild soybean G. soja × cultivated soybean Glycine max. Simulation started with ten F (1) and 990 wild soybeans reproducing by selfing or outcrossing. Seed production was determined from the genetic effects of two QTLs for number of seeds (SN). Each seed survived winter according to the maternal genotype at three QTLs for winter survival (WS). We assumed that one neutral transgene was inserted at various sites and calculated its extinction rate. The presence of G. max alleles at SN and WS QTLs significantly decreased the probability of introgression of the neutral transgene at all insertion sites equally. The presence of G. max alleles at WS QTLs lowered the risk more than their presence at SN QTLs. Although most model studies have concentrated only on genotypic effects of transgenes, we show that the presence of fitness-related domestication genes has a large effect on the risk of transgene escape. Our model offers the advantage of considering the effects of both domestication genes and a transgene, and they can be widely applied to other wild × crop relative complexes.

Cross-Sectional Associations of Sarcopenia and Its Components with Neuropsychological Performance among Memory Clinic Patients with Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The association of sarcopenia with cognitive function in its specific domains remains poorly understood. OBJECTIVES: To investigate the association of sarcopenia and its components with neuropsychological performance among patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). DESIGN: Cross-sectional design. SETTING: A memory clinic in Japan. PARTICIPANTS: The study included 497 MCI/684 AD patients aged 65-89 years. MEASUREMENTS: Patients were assessed for muscle mass by bioelectrical impedance analysis, muscle strength by hand grip strength (HGS), and physical performance by timed up and go test (TUG). Sarcopenia was defined as presence of both low muscle strength and low muscle mass. The patients underwent neuropsychological tests, including logical memory, frontal lobe assessment battery, word fluency test, Raven's colored progressive matrices, digit span, and the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog). RESULTS: The prevalence of sarcopenia in men and women was 24.1% and 19.5%, respectively. In multiple regression analyses adjusting for confounders, unlike in men, sarcopenia was associated with memory function in women (ADAS-cog, memory domain, coefficient = 1.08, standard error (SE) = 0.36), which was thought likely due to the relationship between HGS and memory function (immediate recall of logical memory, coefficient = 0.07, SE = 0.03; ADAS-cog, memory domain, coefficient = -0.10, SE = 0.03). Of the components of sarcopenia in both sexes, HGS and TUG were associated with visuospatial function and frontal lobe function, respectively. CONCLUSIONS: The specific association of sarcopenia and its components with cognitive domains may provide the key to elucidating the muscle-brain interactions in AD.

Expansion of iNKT Cells Promotes Liver Repair Following Hepatic Ischemia Reperfusion Injury.

BACKGROUND/AIM: Invariant natural killer T (iNKT) cells are involved in the initiation and resolution of inflammatory responses. We previously reported that activated iNKT cells facilitate liver repair after hepatic ischemia reperfusion (I/R) injury by accelerating macrophage polarization during the early phase of hepatic I/R injury. Upon activation with α-galactosylceramide (α-GalCer), iNKT cell numbers transiently decrease before increasing within 72 h of stimulation. In the present study, we examined the role of expanded hepatic iNKT cells in the late phase of hepatic I/R injury. MATERIALS AND METHODS: iNKT cells were activated by intraperitoneal injection of α-GalCer in male C57/BL6 mice at the induction of hepatic ischemia followed by reperfusion. RESULTS: Numbers of activated hepatic iNKT cells immediately diminished after hepatic I/R and reached minimal levels at 24 h and 48 h post-reperfusion. Numbers of hepatic iNKT cells then increased at 72 h and 96 h post-reperfusion to levels approximately 2-fold higher than in mice that underwent a sham operation. Liver repair as demonstrated by decreased necrotic area and increased expression of proliferating cell nuclear antigen (PCNA) was enhanced in α-GalCer-treated mice at 96 h post-reperfusion. Interleukin (IL)-13 production by proliferating iNKT cells was observed at 96 h post-reperfusion, which was associated with enhanced liver repair and increased numbers of reparative macrophages. CONCLUSION: Repopulation of hepatic iNKT cells promotes liver repair by stimulating macrophage phenotype switching in the late phase of hepatic I/R injury.

Development of an application tool to support returnees in Fukushima.

To promote radiation protection and health promotion among returning residents (returnees) in coastal areas of Fukushima, eHealth principles were used to develop a new application tool (app) that can record radiation exposure and health status while providing comprehensive support to returnees. Intended users are returnees and health and welfare workers. After assessing their needs, a flowchart and prototype for operational logic were created using commercially available software tools. Professional developers will focus on improving the user interface and ensuring data security. The finished app will be compatible with mobile telephones and tablets. Utility and ease of use are paramount to serve returnees of all ages effectively.

The origin and fate of morphological intermediates between wild and cultivated soybeans in their natural habitats in Japan.

The spread of transgenes into the genome of wild soybean is a concern when transgenic and wild soybeans are planted sympatrically. The objectives of this study were to investigate the origin and fate of morphological intermediates between wild and cultivated soybeans in their natural habitats in Japan. Twenty nuclear microsatellite and two chloroplast dCAPS markers were used to evaluate genetic variation of 468 wild, 17 intermediate, and 12 cultivated soybean samples collected from six sites between 2003 and 2006. Allelic differentiation of microsatellite markers between wild and cultivated soybeans was sufficient to detect their hybrids. Based on levels of observed heterozygosity, intermediate soybean plants were from two generations: either F(1) or an early segregating generation. Genetic admixture analysis and parentage assignment analysis revealed that the parents of all intermediate soybean plants could be assigned to a particular wild soybean plant and late-maturing cultivar. The chloroplast DNA haplotypes revealed that all intermediate soybean plants originated from gene flow from cultivated to wild soybeans at all sites. Based on monitoring at both the phenotypic and molecular levels, hybrids quickly disappeared from natural habitats, and secondary gene flow from these plants to wild soybean was not detected. Thus, while gene flow from transgenic soybean into wild soybean can occur, gene introgression appears to be rare in natural habitats in Japan. This is the first report on the detection of gene flow from cultivated to wild soybean at the molecular level.

Insulin-mediated regulation of decidual protein induced by progesterone (DEPP) in adipose tissue and liver.

We analyzed the profile of the genes expressed in human adipose tissue and identified the fat-derived molecules, adiponectin and aquaporin 7, which modulate glucose and lipid metabolism. The same Bodymap analysis revealed abundant expression of the decidual protein induced by progesterone (DEPP) in the white adipose tissue. Northern blot analysis confirmed that human DEPP mRNA was highly expressed in white adipose tissue. Mouse DEPP mRNA was detected in heart, lung, skeletal muscle, and white adipose tissue under feeding state. In contrast, under fasting state, mouse DEPP mRNA was enhanced in lung, skeletal muscle, and white adipose tissue and it appeared also in the liver and kidney, suggesting up regulation of DEPP by fasting. Because fasting-induced DEPP expression was observed in insulin-sensitive organs, we investigated the regulation of DEPP in white adipose tissue and liver. During adipogenesis of mouse 3T3-L1 cells, DEPP mRNA increased in a differentiation-dependent manner similar to adiponectin and aquaporin 7. Treatment of cultured 3T3-L1 mature adipocytes, rat H4IIE, and human HepG2 hepatoma cells with insulin significantly decreased DEPP mRNA levels in dose- and time-dependent manners. IN VIVO experiments showed significant decrease of hepatic and adipose DEPP mRNA levels in refed mice, compared to fasted animals, and also showed significant increase in DEPP mRNA in streptozotocin-induced insulin-deficient diabetic mice. These results indicate that DEPP is a novel insulin-regulatory molecule expressed abundantly in insulin-sensitive tissues including white adipose tissue and liver.

Hypermethylation-mediated reduction of WWOX expression in intraductal papillary mucinous neoplasms of the pancreas.

We have previously shown that WW domain-containing oxidoreductase (WWOX) has tumour-suppressing effects and that its expression is frequently reduced in pancreatic carcinoma. In this study, we examined WWOX expression in intraductal papillary mucinous neoplasm of the pancreas (IPMN) to assess the function of WWOX in pancreatic duct tumourigenesis using immunohistochemistry and methylation-specific polymerase chain reaction analysis. Among 41 IPMNs including intraductal papillary mucinous adenomas (IPMAs) and intraductal papillary mucinous carcinomas (IPMCs), loss or reduced WWOX immunoreactivity was detected in 3 (15%) of 20 IPMAs and 17 (81%) of 21 IPMCs. In addition, hypermethylation of the WWOX regulatory site was detected in 1 (33%) of 3 WWOX(-) IPMAs and 9 (53%) of 17 WWOX(-) IPMCs, suggesting that hypermethylation may possibly be important in the suppression of WWOX expression. Reduction of WWOX expression was significantly correlated with a higher Ki-67 labelling index but was not correlated with the ssDNA apoptotic body index. Interestingly, decreased WWOX expression was significantly correlated with loss of SMAD4 expression in these IPMNs. The results indicate that downregulation of WWOX expression by the WWOX regulatory region hypermethylation is critical for transformation of pancreatic duct.

N-acetylhistidine isolated from frog heart.

A diazo-positive comitpound was found in an extract of frog heart. This substance showed a negative ninhydrin reaction and had on a paper chromatogram developed with a phenol-hydrochloric acid solvent system a higher R(F) than carnosine. The substance, isolated by chrolnatography, was identified as N-acetyl-L-histidine.

The effect of posttranslational modifications on the interaction of Ras2 with adenylyl cyclase.

Ras proteins undergo a series of posttranslational modifications that are critical for their cellular function. These modifications are necessary to anchor Ras proteins to the membrane. Yeast Ras2 proteins were purified with various degrees of modification and examined for their ability to activate their effector, adenylyl cyclase. The farnesylated intermediate form of Ras2 had more than 100 times higher affinity for adenylyl cyclase than for the unprocessed form. The subsequent palmitoylation reaction had little effect. In contrast, palmitoylation was required for efficient membrane localization of the Ras2 protein. These results indicate the importance of farnesylation in the interaction of Ras2 with its effector.

Polyamines inhibit the protein kinase 380--catalyzed phosphorylation of eukaryotic initiation factor 2 alpha.

Polyamines putrescine, spermidine, and spermine specifically inhibit the PK 380--catalyzed phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha). Since te PK 380--dependent phosphorylation of eIF-2 alpha inhibits the initiation or protein synthesis, the possibility exists that the polyamines enhance protein synthesis by inhibiting the phosphorylation of eIF-2 alpha by PK 380.

[Aortic valve replacement through right thoracotomy; report of a case].

A 78-year-old female was admitted to our hospital with a diagnosis of severe aortic valve regurgitation. She had had dyspnea on effort and syncope twice in 5 months. She had also suffered from right pneumonia 8 years before, and her respiratory function was severely constrictive. Chest X-ray showed her mediastinum significantly shifted toward the right side. Chest computed tomography (CT) revealed the main pulmonary artery, right atrium (RA) and right pulmonary veins also shifted toward the right. We planned right thoracotomy at 4th intercostals space to obtain a good surgical field. A cardiopulmonary bypass was established by RA appendage drainage and femoral artery perfusion. Aortic valve replacement(AVR) was performed successfully after aortic clamp. Though defibrillator pads were placed on her back and the anterior wall of the left chest during operation, no ventricular fibrillation occurred. AVR via right thoracotomy is considered to be a good option for such a mediastinum shifted case.

[Infective endocarditis with acute embolism to the lower extremity artery caused by a vegetation: report of a case].

Successful surgical treatment of a case of infective endocarditis with embolism to a lower extremity artery is reported. A 71-year-old man was referred to our hospital for the treatment of infective endocarditis. Echocardiography showed a vegetation on the non-coronary cusp of the aortic valve measuring 19 mm in diameter. We planned surgical treatment, including aortic valve replacement, however, embolism of a lower extremity artery by the vegetation occurred during the waiting period for the operation. We removed the offending vegetation from the popliteal artery and replaced the peccant aortic valve with a prosthetic valve in separate operations. The postoperative course was uneventful and the patient was transferred to another hospital on the 33rd day after the valve replacement surgery.