Preparatory Knee Flexion-Extension Movements Enhance Rapid Sidestepping Performance in Collegiate Basketball Players.

Lower-limb weight-bearing load distribution in stationary standing influences the timing of rapid first step initiation of importance for functional movement activities and agility performance in sports. This study investigated the effect of pre-step lower-limb loading and unloading with preparatory knee flexion-extension movements on sidestepping performance in fifteen male collegiate basketball players. Participants performed two-choice (step limb) reaction time sidestepping under two conditions: without preparatory movements before the go cue (no-prep-NP) and with continuous alternating knee extension and flexion movements (prep-P). The reaction signal was provided at the beginning of knee extension and flexion and during these movements which corresponded with the largest and smallest loading instants and the transition states between those instants. Sidestepping performance was assessed with three-dimensional kinematic data and ground reaction forces. Step initiation onset time was significantly faster by 13-15% than the NP condition when initiated in the knee flexion phase (p ≤ 0.028, r ≥ 0.70), whereas step-limb unloading interval from step initiation to step lift-off was significantly faster by 12-15% in the knee extension phase (p ≤ 0.01, r ≥ 0.74). The preparatory movements significantly shortened step lift-off by 10-12% (p ≤ 0.013, r ≥ 0.73) and step duration by 17-21% (p < 0.001, r ≥ 0.85) with 19-22% faster step velocity (p < 0.001, r ≥ 0.84), which resulted in 14-15% shorter overall time to step landing (p < 0.001, r ≥ 0.84), irrespective of the loading phases. These results indicated that lower-limb loading with pre-step knee flexion facilitated faster step initiation, while lower-limb unloading with knee extension facilitated faster step-limb unloading, both resulting in faster step lift-off. Bilateral knee flexion-extension movements as a preparatory action could be utilized by invasion sports players to facilitate reactive stepping performance for more effective movement initiation.

Comparison of the proteomes in sera between healthy Thoroughbreds and Thoroughbreds with respiratory disease associated with transport using mass spectrometry-based proteomics.

In the past decade, mass spectrometry has become an important technology for protein identification. Recent developments in mass spectrometry allow a large number of identifications in samples; therefore, mass-spectrometry-based techniques have been applied to the discovery of biomarkers. Here, we conducted a proteomic study to compare the proteomes in sera between healthy Thoroughbreds and Thoroughbreds with respiratory disease associated with transport (RDT). We found that four proteins, apolipoprotein F, lipopolysaccharide binding protein, lysozyme and protein S100-A8, were upregulated, while keratin 1 was downregulated in the RDT group. It is assumed that inflammation and immune response are involved in the changes of these proteins. The findings suggested that these proteins are potentially useful for elucidating the mechanism of development of RDT.

An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury.

Preventing clinical drug-induced liver injury (DILI) remains a major challenge, because DILI develops via multifactorial mechanisms. Immune and inflammatory reactions are considered important mechanisms of DILI; however, biomarkers from in vitro systems using immune cells have not been comprehensively studied. The aims of this study were (1) to identify promising biomarker genes for predicting DILI in an in vitro coculture model of peripheral blood mononuclear cells (PBMCs) with a human liver cell line, and (2) to evaluate these genes as predictors of DILI using a panel of drugs with different clinical DILI risk. Transcriptome-wide analysis of PBMCs cocultured with HepG2 or differentiated HepaRG cells that were treated with several drugs revealed an appropriate separation of DILI-positive and DILI-negative drugs, from which 12 putative biomarker genes were selected. To evaluate the predictive performance of these genes, PBMCs cocultured with HepG2 cells were exposed to 77 different drugs, and gene expression levels in PBMCs were determined. The MET proto-oncogene receptor tyrosine kinase (MET) showed the highest area under the receiver-operating characteristic curve (AUC) value of 0.81 among the 12 genes with a high sensitivity/specificity (85/66%). However, a stepwise logistic regression model using the 12 identified genes showed the highest AUC value of 0.94 with a high sensitivity/specificity (93/86%). Taken together, we established a coculture system using PBMCs and HepG2 cells and selected biomarkers that can predict DILI risk. The established model would be useful in detecting the DILI potential of compounds, in particular those that involve an immune mechanism.

Percent reduction of the ulcer size at 4 weeks is a predictor of the complete healing of endoscopic submucosal dissection-induced gastric ulcers.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is widely used as a treatment modality for gastric mucosal neoplasia. While proton pump inhibitors (PPIs) have been used for the control of artificial ulcers created by ESD (ESD-ulcers), complete healing of the ulcers is not always achieved in all the cases. The purpose of this study was to identify the clinical factors that are predictive of refractory ESD-ulcers. PATIENTS AND METHODS: We recruited 90 patients with 102 artificial ulcers that formed after the patients underwent ESD for gastric tumours. All the patients received a 20-mg capsule of esomeprazole daily until the 56th day after ESD, and underwent endoscopy at 1, 4, 6 and 8 weeks after the ESD. We analyzed the clinical factors that were associated with the complete healing at 8 weeks after the ESD (CH-8w). The ulcers in the scar stage were defined as the complete healing in this study. RESULTS: Of the 102 ESD-ulcers, 16.7% failed to show complete healing after the 8 weeks of PPI therapy. Univariate analysis identified the percent reduction of the ulcer size at 4 weeks after ESD (PR-4w) as being significantly associated with CH-8w. Multivariate analysis identified ulcer location in the lower-third of the stomach and PR-4w > 95% as being independently correlated with the CH-8w (odds ratio = 4.86 and 7.89, respectively). Analysis of the area under the receiver operating characteristic (AUROC) curve demonstrated that the AUROC curve of PR-4w for predicting the CH-8w was 0.78. CONCLUSION: Based on the results of our study, endoscopic observation at 4 weeks after ESD would help in the early identification of refractory ESD-ulcers.

Distribution of regulatory T cells in inflammatory colorectal polyps of miniature dachshunds.

Inflammatory colorectal polyp (ICRP) is an emerging disease in Miniature Dachshunds (MDs). Animals with this disease exhibit multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Macrophages in polypoid lesions have been described to play an important role in neutrophil infiltration in the lesion by producing IL-8. In contrast, IL-10, an anti-inflammatory cytokine, was also reported to be upregulated in polypoid lesions, but its significance in the pathogenesis of ICRP has not been clarified. Regulatory T cells (Tregs) are the main source of IL-10 production and contribute to the maintenance of intestinal homeostasis. Therefore, the objective of this research was to compare the distribution of Tregs in polypoid lesions of ICRPs and the association between the distribution and expression of pro- or anti-inflammatory cytokines. Tissue biopsy specimens of polypoid lesions were collected from 28 MDs with ICRP. Those of macroscopically non-polypoid colonic mucosa from 24 MDs with ICRPs and 21 control dogs were further included as controls. Real-time quantitative polymerase chain reaction was used to quantify gene expression of IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22, IFN-γ, TNF-α, TGF-ß, and forkhead box protein P3 (Foxp3) in each tissue sample. The numbers of Foxp3-positive cells (Tregs) and ionized calcium binding adapter molecule 1 (Iba-1)-positive cells (macrophages) were determined by immunohistochemistry. The gene expression of IL-1ß, IL-6, IL-8, TNF-α, IFN-γ, IL-17, IL-10, TGF-ß, and Foxp3 was significantly upregulated in polypoid lesions relative to control levels. The numbers of Foxp3-positive Tregs and Iba-1-positive macrophages were significantly increased in polypoid lesions compared to those in the non-polypoid colonic mucosa of MDs with ICRPs and control dogs. The upregulation of IL-10 was moderately correlated with the distribution of Tregs in polypoid lesions from MDs with ICRPs. In addition, the relative upregulation of IL-1ß, IL-6, and IL-8 in polypoid lesions, compared to expression in non-polypoid colonic mucosa of MDs with ICRPs, was significantly greater than that of IL-10. These results indicate that increases in Treg numbers and anti-inflammatory cytokines in polypoid lesions comprise reactive changes in response to the inflammation, which warrants further investigation.

Histopathologic Features of Colorectal Adenoma and Adenocarcinoma Developing Within Inflammatory Polyps in Miniature Dachshunds.

Biopsy samples of colorectal polyps were collected and examined from 67 Miniature Dachshund dogs (including 35 cases with an additional biopsy). Histopathologic diagnoses of the initial biopsy samples were "inflammatory polyp" in 52 cases (78%), "adenoma" in 10 cases (15%), and "adenocarcinoma" in 5 cases (8%). Eight of 10 cases (80%) diagnosed as adenoma also had inflammatory polyp lesions in the same specimen. A second biopsy was performed in 25 cases (48%) initially diagnosed with inflammatory polyp. Pathologic diagnoses for the second biopsy were inflammatory polyp in 11 cases (44%), adenoma in 9 cases (36%), and adenocarcinoma in 5 cases (20%). The number of beta-catenin-positive nuclei in epithelial cells was significantly higher in adenoma (46%) and adenocarcinoma (75%) as compared with inflammatory polyp (6%). Normal epithelial cells and hyperplastic goblet cells in inflammatory polyps showed homogeneous positive cytoplasmic immunoreactivity for adenomatous polyposis coli (APC) antigen. However, APC expression was decreased in areas of intense nuclear beta-catenin expression in adenoma and adenocarcinoma lesions. Foci of cytokeratin 5/6-positive squamous cell-like neoplastic cells showed intense beta-catenin nuclear expression that was similar to squamous morules described in human colorectal tumors. The results of the present study suggest that the inflammatory polyp in Miniature Dachshunds is a progressive disease that may develop into adenoma and/or adenocarcinoma. In addition, immunohistochemical findings suggest that aberrations of APC and beta-catenin expression may be involved in tumor development within the inflammatory polyp lesions.

Association between endoscopic findings related to colonic diverticula and bowel habits: A multicenter study in Japan.

BACKGROUND AND AIM: Few studies have shown the associations between colonic diverticula and endoscopic findings such as location, inflammation, number of diverticula, sigmoid colon rigidity, and bowel habits. METHODS: Japanese subjects who underwent total colonoscopies at six centers in Japan from November 2015 to October 2016 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale. Location and number of diverticula, inflammation, and sigmoid colon rigidity were evaluated from endoscopy results. RESULTS: A total of 762 subjects (486 men and 276 women [ratio, 1.76:1]) whose mean age was 65.5 ± 11.4 years were evaluated. In multivariate analysis, presence of constipation was associated with a significantly lower likelihood of left-sided colonic diverticula (odds ratio = 0.40, 95% confidence interval 0.20-0.82, P = 0.012), whereas right-sided and bilateral-sided colonic diverticula, multiple colonic diverticula, inflammation findings, and sigmoid colon rigidity were not related to bowel habits. CONCLUSIONS: Among endoscopic findings related to colonic diverticula and bowel habits, only left-sided colonic diverticula were inversely associated with constipation, whereas inflammation findings, multiple diverticula, and sigmoid colon rigidity were not related to bowel habits. However, the association of inflammation findings with colonic diverticula and bowel habits should be further studied. Investigation of changes in left-sided colonic diverticula may lead to new treatments for constipation.

Factors associated with poor therapeutic response in outpatients with irritable bowel syndrome: a multicenter study in Japan.

BACKGROUND: Some patients with irritable bowel syndrome (IBS) show poor response to treatment. However, risk factors associated with poor therapeutic response have not been determined. METHODS: This multicenter trial evaluated consecutive outpatients with IBS undergoing treatment for more than 1 month. Mental health status and physical function were evaluated using the Japanese version of the SF-8. Therapeutic response was evaluated using the IBS severity index-Japanese version (IBS-SIJ). Patients with IBS-SIJ scores ≥175 were defined as poor responders to treatment, whereas those with IBS-SIJ scores <175 were defined as good responders. The demographic and clinical characteristics of these two groups, along with medications, were compared. RESULTS: The study enrolled 131 participants, 75 with IBS-SIJ scores ≥175-56 with IBS-SIJ scores <175. Multiple logistic regression analysis showed that female sex [odds ratio (OR) 2.67, 95 % confidence interval (CI) 1.19-5.97, p = 0.0167] and mental component summary (MCS) of the SF-8 <40 (OR 2.58, 95 % CI 1.12-5.97, p = 0.0263) were independent risk factors for poor therapeutic response in patients with IBS. CONCLUSIONS: Lower MCS and female sex were risk factors for poor therapeutic response in patients with IBS. Ascertaining the mechanisms by which lower MCS and female sex are associated with poor therapeutic response in IBS may help design better treatments (Trial registration number: UMIN000016804).

Polymorphisms of nucleotide-binding oligomerization domain 2 (NOD2) gene in miniature dachshunds with inflammatory colorectal polyps.

Inflammatory colorectal polyps (ICRPs) frequently occur in miniature dachshunds (MDs) in Japan, typically form multiple polyps with severe neutrophil infiltration. ICRPs are speculated as a novel, breed-specific canine inflammatory bowel disease. Pattern recognition receptors (PRRs) play an important role in the differentiation of pathogens from commensal bacteria and food antigens, and polymorphisms of various PRRs have been shown to be associated with human and canine IBD. We recently reported that the reactivity of nucleotide-binding oligomerization domain 2 (NOD2), toll-like receptor (TLR) 1/2, TLR2, and TLR2/6 are greater in ICRP-affected MDs than that in controls. Therefore, this study was aimed to investigate single nucleotide polymorphisms (SNPs) of PRRs associated with ICRPs in MDs. Mutational analysis of canine NOD2, TLR1, TLR2, and TLR6 genes was performed with six ICRP-affected MDs, five control MDs, and five healthy beagles. The mutational analysis identified 13 non-synonymous SNPs in NOD2, TLR1, TLR2, and TLR6 genes, of which six SNPs in NOD2 exon 3 were further analyzed in an association study using 63 ICRP-affected MDs, 82 control MDs, and 237 control dogs of various breeds. Four of the SNPs (A1532G, T1573C, C1688G, and G1880A of the NOD2 gene) were in Hardy-Weinberg equilibrium and in complete linkage disequilibrium in MDs, and their minor allele frequencies were significantly lower in ICRP-affected MDs than in control MDs (0.016 vs. 0.140, P=0.0002). The calculated inheritance model was an additive model (odds ratio=0.10, 95% confidence interval=0.02-0.45, P=0.0001), which indicates that the haplotype with minor alleles in these SNPs (A, T, C, and G in A1532G, T1573C, C1688G, and G1880A) possess a protective effect regarding the development of ICRPs. However, these SNPs were not specific for MDs, although the minor allele frequencies of these SNPs in control MDs were significantly lower than in other breed dogs. These results suggest that the identified four SNPs (A1532G, T1573C, C1688G, and G1880A in the NOD2 gene) may play a role in the pathogenesis of ICRPs in MDs. Because the majority of MDs and other breed dogs do not have the protective alleles, their absence may not be a specific cause of ICRPs in MDs but rather contribute to the development of inflammation.

Association between the location of diverticular disease and the irritable bowel syndrome: a multicenter study in Japan.

OBJECTIVES: No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS). METHODS: We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. RESULTS: Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. CONCLUSIONS: Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).

Metabolic factors accelerate colorectal adenoma recurrence.

BACKGROUND: Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors. METHODS: We analyzed the medical records of 43,195 patients who had undergone colonoscopy between January 2005 and December 2011 at 5 hospitals in Japan. Of these, the data of 1111 patients who had undergone removal of adenomas at the first screening colonoscopy, and then been followed up by colonoscopy 1 year and 2 years later were analyzed. RESULTS: The following 8 factors were demonstrated with a multivariate analysis as being associated with colorectal adenomas recurrence: for adenoma-related factors, 5 factors (villous features, grade of dysplasia, location and size of the largest removed adenoma, and number of the removed adenomas) were identified; for metabolic factors and other factors, 3 factors (age, body mass index (BMI), and fasting blood glucose (FBG)) were identified. A risk score (0-10 points) was developed based on these 8 factors. The risk of adenoma recurrence increased as the risk score increased. When the risk score was ≥3 (3-10) points, the odds ratio relative to <3 (0-2) points was 7.07 (95% CIs 5.30-9.43). CONCLUSIONS: In addition to adenoma-related factors (villous features, grade of dysplasia, location, size and number), 3 factors (age, BMI and FBG) were demonstrated to influence the recurrence rate of colorectal adenoma. When the risk score was ≥3, the risk of recurrence was significantly elevated.

Visceral obesity as a risk factor for left-sided diverticulitis in Japan: a multicenter retrospective study.

BACKGROUND/AIMS: Left-sided diverticulitis is increasing in Japan, and many studies report that left-sided diverticulitis is more likely to be severe. Therefore, it is important to identify the features and risk factors for left-sided diverticulitis. We hypothesized that left-sided diverticulitis in Japan is related to obesity and conducted a study of the features and risk factors for this disorder in Japan. METHODS: Right-sided diverticulitis and left-sided diverticulitis patients (total of 215) were compared with respect to background, particularly obesity-related factors to identify risk factors for diverticulitis. RESULTS: There were 166 (77.2%) right-sided diverticulitis patients and 49 (22.8%) left-sided diverticulitis patients. The proportions of obese patients (body mass index ≥25 kg/m(2), p=0.0349), viscerally obese patients (visceral fat area ≥100 cm(2), p=0.0019), patients of mean age (p=0.0003), and elderly patients (age ≥65 years, p=0.0177) were significantly higher in the left-sided-diverticulitis group than in the right-sided-diverticulitis group. The proportion of viscerally obese patients was significantly higher in the left-sided-diverticulitis group than in the left-sided-diverticulosis group (p=0.0390). CONCLUSIONS: This study showed that obesity, particularly visceral obesity, was a risk factor for left-sided diverticulitis in Japan.

[Disseminated varicella-zoster virus infection complicated with severe abdominal pain and colonic pseudo-obstruction].

A 48-year-old man was admitted to our hospital complaining of acute severe abdominal pain and constipation. He had received bone marrow transplantation for acute myelogenous leukemia 5 months previously and immunosuppressant treatment for chronic graft-versus-host disease. Abdominal X-ray and CT scan films revealed his large intestine widely dilated and filled with air, and colonic pseudo-obstruction was diagnosed. It was difficult to ascertain the cause of the symptoms until 6 days after onset of the abdominal pain when disseminated zoster eruption appeared over his whole body. It was disseminated varicella-zoster and complicated with colonic pseudo-obstruction. He was treated with acyclovir. It is important to suspect disseminated varicella-zoster and treat early immunocompromised patients complaining of severe acute abdominal pain and colonic pseudo-obstruction.