Modelling the invasion of human small intestinal epithelial-like cells by Salmonella enterica Typhimurium and Listeria monocytogenes using Bayesian inference.

To develop a mechanistic bacterial dose-response model, based on the concept of Key Events Dose-Response Framework (KEDRF), this study aimed to investigate the invasion of intestinal model cells (Caco-2) by Salmonella Typhimurium and Listeria monocytogenes and described the behaviour of both pathogens as a mathematical model using Bayesian inference. Monolayer-cultured Caco-2 cells (approximately 105 cells) were co-cultured with various concentrations (103 -107 colony forming unit [CFU] ml-1 ) of Salm. Typhimurium and L. monocytogenes for up to 9 h to investigate the invasion of the pathogens into the Caco-2 cells. While an exposure of ≥103 CFU ml-1 of Salm. Typhimurium initiated the invasion of Caco-2 cells within 3 h, much less exposure (102 CFU ml-1 ) of L. monocytogenes was sufficient for invasion within the same period. Furthermore, while the maximum number of invading Salm. Typhimurium cells reached by approximately 103 CFU cm-2 for 6-h exposure, the invading maximum numbers of L. monocytogenes cells increased by approximately 106 CFU cm-2 for the same exposure period. The invasion kinetics of both the pathogens was successfully described as an asymptotic exponential mathematical model using Bayesian inference. The developed pathogen invasion model allowed the estimation of probability of Salm. Typhimurium and L. monocytogenes infection, based on the physiological natures of digestion process, which was comparable to the published dose-response relationship. The invasion models developed in the present study will play a key role in the development of an alternative pathogen dose-response model based on KEDRF concept.

Atomic step-and-terrace surface of polyimide sheet for advanced polymer substrate engineering.

Typical thermostable and flexible polyimide polymers exhibit many excellent properties such as strong mechanical and chemical resistance. However, in contrast to single-crystal substrates like silicon or sapphire, polymers mostly display disordered and rough surfaces, which may result in instability and degradation of the interfaces between thin films and polymer substrates. As a step toward the development of next-generation polymer substrates, we here report single-atom-layer imprinting onto the polyimide sheets, resulting in an ultrasmooth 0.3 nm high atomic step-and-terrace surface on the polyimides. The ultrasmooth polymer substrates are expected to be applied to the fabrication of nanostructures such as superlattices, nanowires, or quantum dots in nanoscale-controlled electronic devices. We fabricate smooth and atomically stepped indium tin oxide transparent conducting oxide thin films on the imprinted polyimide sheets for future use in organic-based optoelectronic devices processed with nanoscale precision. Furthermore, toward 2D polymer substrate nanoengineering, we demonstrate nanoscale letter writing on the atomic step-and-terrace polyimide surface via atomic force microscopy probe scratching.

The Relation between Hamstring Strain Injury and Physical Characteristics of Japanese Collegiate Sepak Takraw Players.

The aim of this study was to investigate the injuries in Japanese collegiate sepak takraw players. We primarily focused on hamstring strain injury (HSI), and investigated the associated physical characteristics. The study included 77 Japanese collegiate sepak takraw players who were interviewed; data were collected regarding injuries sustained by them during the game within the past year. The hip range of motion (ROM) was measured. The total number of injuries was 48 in a year. The rate of HSI was the highest (31.3%) among all the injuries. All HSIs occurred in the dominant leg because of the sunback spike. Using the Mann-Whitney U test, significant differences in age and sport-related experience were observed between the injured group and uninjured group. Upon using logistic regression analysis, the presence of a HSI was found to be associated with the sport-related experience (adjusted odds ratio [OR], 0.30; 95% confidence interval [CI], 0.12-0.77) and the hip extension ROM (adjusted OR, 0.81; 95% CI, 0.66-0.99) after adjusting for sex, sport-related experience, and the hip ROM. HSI is the most common injury in Japanese collegiate sepak takraw players. Short sport-related experience and small hip extension ROM are related with the occurrence of HSI.

Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis.

Thymic stromal lymphopoietin (TSLP) has been suggested recently to play an important role in the pathophysiology of rheumatoid arthritis (RA). However, there is little information on serum TSLP concentrations in RA and its clinical significance. The present study investigated whether serum TSLP concentrations were affected in patients with RA. Using an enzyme-linked immunosorbent assay (ELISA), we measured TSLP concentrations in the serum obtained from 100 patients with RA, 60 patients with osteoarthritis (OA) and 34 healthy volunteers. We also investigated the correlation between serum TSLP concentrations and clinical parameters of disease activity in RA [disease activity score using 28 joint counts (DAS28)-C-reactive protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI]), patient's/-physician's Visual Analogue Scale (VAS), swollen joints count, tender joints count, CRP, ESR and matrix metalloproteinase-3 (MMP-3) concentrations]. In addition, we investigated the correlation between serum TSLP concentrations and anti-citrullinated peptide antibody (ACPA) and serum tumour necrosis factor (TNF)-α. Serum TSLP levels in patients with RA were significantly higher than those in patients with OA and in healthy volunteers. Interestingly, serum TSLP concentrations were correlated significantly with ACPA titres, but not with other clinical parameters. There was a significant increase in serum TSLP concentrations in patients with RA, which was correlated positively with serum ACPA titres. These findings suggest that in patients with RA, TSLP may play a role in ACPA production by B cells.

Influence of Ankle Braces on the Maximum Strength of Plantar and Toe Flexor Muscles.

This study sought to investigate the influence of ankle braces on maximum strength of plantar and toe flexor muscles. 21 healthy participants volunteered, and their maximum isometric toe flexor muscle strength (TFS), plantar flexor muscle strength (PFS) and passive range of motion of the ankle joint (ROM) were measured. TFS, PFS and ROM were compared among barefoot as a control (BAR), ankle support (SUP) and ankle splint (SPL) conditions. TFS was significantly lower in SPL (90.7±32.5 N, p<0.0001) compared to BAR (117.3±39.5 N) and it was significantly lower in SPL than in SUP (110.5±36.7 N, p=0.0001), whereas it was not significantly different between SUP and BAR (p=0.2587). On the contrary, PFS and ROM were significantly lower in SUP (p=0.0087 for PFS; p=0.0095 for ROM) and SPL (p<0.0001 for PFS; p<0.0001 for ROM) compared to BAR, and they were significantly lower in SPL than in SUP (p=0.0073 for PFS; p<0.0001 for ROM). The ankle support could provide ankle joint stabilization without a large decrease in the muscle strength of the foot. The proper use of an ankle brace is required to prevent major impairment of the muscle functions of the ankle-foot complex.

Radiological abnormalities and low back pain in gymnasts.

Several studies have shown a higher prevalence of radiological abnormalities among gymnasts. However, the types of radiological abnormalities associated with low back pain (LBP) have not been clarified. The hypothesis was that significant relationships between radiological abnormalities and LBP may be revealed by discriminating between the types of MRI abnormalities while considering confounding factors. The subjects were 104 Japanese collegiate gymnasts (men, 70; women, 34). The presence of LBP was evaluated using the questionnaire developed by Osaka City University (OCU Test). Magnetic resonance imaging (MRI) abnormalities were evaluated using T1- and T2-weighted MRI. The prevalence of more than 1 MRI abnormality in gymnasts was 47.1% (49/104). The chi-square test showed that the incidence of lumbar disc degeneration (LDDG) and limbus vertebra was significantly greater in gymnasts with LBP than in gymnasts without LBP. By using logistic regression analysis to analyze the concomitant environmental variables, only LDDG (odds ratio, 2.70; 95% confidence interval, 1.10-6.66) was selected as a statistically significant variable accounting for LBP. In conclusion, LDDG is a predictor for LBP in Japanese collegiate gymnasts.

ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

Insulinoma may mask the existence of Type 1 diabetes.

BACKGROUND: Insulinoma is a tumour of insulin-producing cells of the pancreas and is known to be one of the causes of hypoglycaemia. Usually, appropriate removal of the insulinoma results in normalization of blood glucose levels. However, we found novel cases of insulinoma, in which hyperglycaemia developed soon after resection of the insulinoma. CASE REPORT: We encountered two patients with repeated hypoglycaemia caused by insulinoma. Following removal of the insulinoma, unanticipated hyperglycaemia was observed in both patients. Thereafter, their blood tests revealed low levels of serum C-peptide and high titres of anti-glutamic acid decarboxylase antibody, indicating concomitant Type 1 diabetes. Indeed, histological examination of the resected specimen revealed that one patient showed insulitis in non-tumorous pancreatic tissue in which ß-cells had already disappeared. Moreover, inflammatory cells infiltrated the insulinoma, as if it were insulitis of Type 1 diabetes, suggesting the existence of anti-islet autoimmunity. CONCLUSION: These are first cases of insulinoma associated with underlying Type 1 diabetes. Physicians should be aware of the possibility that insulinoma may mask Type 1 diabetes, and measurement of anti-islet autoantibodies may be helpful to find underlying Type 1 diabetes, such as in these cases. It is pathologically interesting that the immune cell infiltration into insulinoma may be suggestive of anti-islet autoimmunity.

COL11A1 gene is associated with limbus vertebra in gymnasts.

Several studies have shown higher frequencies of radiological abnormalities among gymnasts. Recently, the gene encoding the α1 chain of type XI collagen, (COL11A1) (rs 1676486), was associated with lumbar disc herniation in the Japanese population. We hypothesized that there was a significant relationship between abnormal magnetic resonance imaging (MRI) findings of the lumbar spine and the COL11A1 4603C/T gene polymorphism in collegiate gymnasts. Our study participants included 103 Japanese collegiate gymnasts (70 men and 33 women). Radiological abnormalities were evaluated using T1- and T2-weighted MRI. Genotyping for COL11A1 was performed for all the participants. By using logistic regression analysis, we observed significant associations between limbus vertebra and age (adjusted odds ratio=0.51, 95% confidence interval: 0.27-0.96), sporting experience (adjusted odds ratio=1.49, 95% confidence interval: 1.14-1.94), and a TT genotype (adjusted odds ratio=7.83, 95% confidence interval: 1.33-46.03). We conclude that a TT genotype of COL11A1 polymorphism may be a significant risk factor for limbus vertebra in Japanese collegiate gymnasts.

[Maxillary and mandibular fractures. Treatment concepts in maxillofacial surgery]. / Frakturen von Maxilla und Mandibula. Kieferchirurgische Behandlungskonzepte.

Maxillary and mandibular fractures are a relatively frequent occurrence due to the exposed location of the jaws and are caused mainly by acts of violence, traffic and recreational accidents. Mandibular fractures can be treated conservatively with dental splints and intermaxillary fixation. Since Michelet, miniplate osteosynthesis via intraoral access has become the method of choice. Champy showed that the monocortical fixation of miniplates at the level of the linea obliqua results in stable osteosynthesis, despite postoperative micro-movements in the fracture gap, and postulated the principle of dynamic compression. Dislocated fractures of the mandibular collum are treated with stable osteosynthesis via an intra- or extraoral approach, while fractures of the mandibular joint are usually treated conservatively and early functional rehabilitation is favored. For mandibular fractures, the principle of load-bearing and load-sharing should be considered, i.e. in the case of sufficient bone and uncomplicated fractures, the bone can bear most of the force, such that miniplates are sufficient (load-sharing). If bones are weakened by atrophy or in the case of infected, comminuted or defect fractures osteosynthesis plates must bear the load alone (load-bearing).

Changes in acyl ghrelin, des-acyl ghrelin, and ratio of acyl ghrelin to total ghrelin with short-term refeeding in female inpatients with restricting-type anorexia nervosa.

Restricting type of anorexia nervosa (AN-R) is a serious disorder affecting adolescents and young adults and decreases quality of life over a long period. Successful weight restoration is an important prognostic factor for disease outcome; however, the underlying mechanism of refeeding resistance, a core psychopathology relevant to 'ambivalent' eating behaviors, remains unclear in this disorder. Ghrelin plays an important role in the regulation of growth hormone release, appetite, and energy metabolism. However, the early progress of these patients and changes in the levels of acyl ghrelin and des-acyl ghrelin during treatment were not reported. The purpose of this study was to determine the changes in ghrelin levels (acyl and des-acyl) during early treatment. As a result, des-acyl ghrelin in AN-R patients is higher than in control subjects before the therapy, but it decreases with treatment. The plasma des-acyl ghrelin level in AN-R patients started decreasing more rapidly and in early stage of the hospitalization than ever reported, and after 8 weeks, it is significantly lower than in control subjects. It means that des-acyl ghrelin is sensitive and changeable with their nutrition state. Furthermore, the ratio of the acyl ghrelin to total ghrelin increases with 8 weeks treatment. Eight weeks after, energy intake of the AN-R patients is recovered near the normal range with a daily energy intake of 1 700+/-93.54 kcal. These findings may be valuable for future AN-R treatments in order to increase acyl ghrelin and decrease des-acyl ghrelin, thereby influencing the refeeding outcome.

Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel neuraminidase inhibitor laninamivir in rats.

CS-8958, a prodrug of laninamivir (R-125489), is currently under development as an inhaled anti-influenza drug. In this study, the pharmacokinetics and disposition of CS-8958 were characterized in rats. After intratracheal administration of 14C-CS-8958, radioactivity was retained over long periods in the target tissues (trachea and lung) as its active metabolite R-125489 - 19.12% of the dose was retained in the lung at 24 h. After intratracheal administration of CS-8958, plasma R-125489 concentration was slowly eliminated, and its half-life (14.1 h) was considerably longer than that after intravenous administration of R-125489. The radioactivity of intratracheally administered 14C-CS-8958 was mainly excreted into the urine (67.5% of dose), and this excretion lasted over long periods. R-125489 accounted for most of the urinary radioactivity recovered after 24 h. These results demonstrated that CS-8958 administered intratracheally to rats was converted/hydrolysed to R-125489 in the target tissues, and that the R-125489 was slowly excreted into the urine via an absorption rate-limiting process. Such distinctive pharmacokinetics attributed to the slow release of R-125489 suggests the potential for a long-acting anti-influenza drug.

Relationship between Histological Grade and Histopathological Appearance in Canine Mammary Carcinomas.

Canine mammary carcinomas are common tumours in female dogs and histopathological examination has an important role in identifying whether they are benign or malignant. The latest and most commonly used histological grading system was established by Peña et al. (2013) and is based on the extent of tubule formation, nuclear pleomorphism and number of mitoses. Before the establishment of this grading system, tumour size and classical histological indicators of malignancy such as lymphovascular invasion, infiltration into surrounding tissue, necrosis and presence of a micropapillary pattern were important predictors of biological behaviour. However, the system of Peña et al. does not consider tumour size or these histological features. Clarifying the association of these features and histological grade, especially in grade II and III carcinomas, is important. In this study, we confirmed that the system of Peña et al. is effective for predicting biological behaviour and that evaluation of histological features of malignancy reinforced histological grade, as determined by the system of Peña et al., especially in grade II carcinomas.

Antibody-mediated bacteriorhodopsin orientation for molecular device architectures.

A rational method for constructing highly oriented films of purple membrane (PM) has been established by using two kinds of bispecific antibodies with different antigen-binding sites, one binding to a specific side of bacteriorhodopsin and the other to a phospholipid hapten. A hapten monolayer deposited on a metal electrode was treated with a bispecific antibody solution and incubated with a PM suspension to produce a highly oriented PM film, as confirmed by electron microscopy in which an immunogold labeling technique was used. This antibody-mediated PM monolayer was then used in the construction of a light-sensing photoelectric device. A comparison of the two incorporated PM monolayers showed that highly efficient photocurrents were produced by the PM monolayer whose unidirectionally oriented cytoplasmic surface faces the electrode.

Quantum conversion and image detection by a bacteriorhodopsin-based artificial photoreceptor.

A thin film (50 to 500 angstroms thick) comprising fragments of bacteriorhodopsin (bR)-containing purple membrane was formed on an SnO(2) conductive electrode by the Langmuir-Blodgett method. The film was put into contact with a thin, aqueous electrolyte gel to construct an electrochemical sandwich-type photocell with a junction structure SnO(2)/bR/electrolyte/Au electrode. Under visible light irradiation, the bR-based photocell produced an efficient rectified photocurrent that proved to have unique differential responsivity to light intensity, which is characteristic of in vivo biological photoreceptors. An artificial photoreceptor comprising a pixel network of the bR photocell was fabricated in an attempt to study image-detecting and processing abilities of bR.

Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.

Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.

Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure.

Prediction of calving time in Holstein dairy cows by monitoring the ventral tail base surface temperature.

Dystocia adversely affects the health of calves and their dams. The aim of this study was to determine whether the ventral tail base surface temperature (ST) could be used to predict calving time in dairy cows. Pregnant Holstein cows were enrolled during the warm season (daily average air temperature 10-20°C; n=13) and cool season (daily average air temperature<10°C; n=22) in Hokkaido, Japan, and a wearable wireless ST sensor was attached to the surface of the ventral tail base of each cow 9-12days before the predicted calving date. The ventral tail base ST was measured every 2min until 24h after calving. Hourly maximum ventral tail base ST values were used in the analysis and changes in ventral tail base ST were expressed as residual temperatures (RTs) to exclude any circadian effects using the formula: RT=actual ST-mean ST for the same hour on the previous 3 days. In both seasons, there was a continual decrease in ventral tail base RT from approximately 24h before calving compared with the control ventral tail base RT from 120 to 97h before calving. The areas under the receiver operating characteristic curves (ROC-AUCs) for ventral tail base RT as a predictor of calving were 0.88-0.95. ROC-AUCs as a predictor of calving within 24h were higher in the warm season than in the cool season. These findings demonstrate that calving time in dairy cows can be predicted by monitoring ventral tail base ST with a wearable wireless sensor, but seasonal variability affects the accuracy of prediction of calving time.

Leptin- or troglitazone-induced lipopenia protects islets from interleukin 1beta cytotoxicity.

Interleukin 1beta (IL-1beta)-induced beta cell cytotoxicity has been implicated in the autoimmune cytotoxicity of insulin-dependent diabetes mellitus. These cytotoxic effects may be mediated by nitric oxide (NO). Since long-chain fatty acids (FFA), like IL-1beta, upregulate inducible nitric oxide synthase and enhance NO generation in islets, it seemed possible that islets might be protected from IL-1beta-induced damage by lowering their lipid content. We found that IL-1beta-induced NO production varied directly and islet cell viability inversely with islet triglyceride (TG) content. Fat-laden islets of obese rats were most vulnerable to IL-1beta, while moderately fat-depleted islets of food-restricted normal rats were less vulnerable than those of free-feeding normal rats. Severely lipopenic islets of rats made chronically hyperleptinemic by adenoviral leptin gene transfer resisted IL-1beta cytotoxicity even at 300 pg/ml, the maximal concentration. Troglitazone lowered islet TG in cultured islets from both normal rats and obese, leptin-resistant rats and reduced NO production and enhanced cell survival. We conclude that measures that lower islet TG content protect against IL-1beta-induced NO production and cytotoxicity. Leptin or troglitazone could provide in vivo protection against insulin-dependent diabetes mellitus.