Dissociation between implicit and explicit responses in postconditioning UCS revaluation after fear conditioning in humans

PubMed Central

Schultz, Douglas H.; Balderston, Nicholas L.; Geiger, Jennifer A.; Helmstetter, Fred J.

2014-01-01

The nature of the relationship between explicit and implicit learning is a topic of considerable debate. In order to investigate this relationship we conducted two experiments on postconditioning revaluation of the unconditional stimulus (UCS) in human fear conditioning. In Experiment 1, the intensity of the UCS was decreased following acquisition for one group (devaluation) and held constant for another group (control). A subsequent test revealed that even though both groups exhibited similar levels of UCS expectancy, the devaluation group had significantly smaller conditional skin conductance responses. The devaluation effect was not explained by differences in the explicit estimates of UCS probability or explicit knowledge that the UCS intensity had changed. In Experiment 2, the value of the UCS was increased following acquisition for one group (inflation) and held constant for another group (control). Test performance revealed that UCS inflation did not alter expectancy ratings, but the inflation group exhibited larger learned skin conductance responses than the control group. The inflation effect was not explained by differences in the explicit estimates of UCS probability or explicit knowledge that the UCS intensity had changed. The SCR revaluation effect was not dependent on explicit memory processes in either experiment. In both experiments we found differences on an implicit measure of learning in the absence of changes in explicit measures. Together, the differences observed between expectancy measures and skin conductance support the idea that these responses might reflect different types of memory formed during the same training procedure and be supported by separate neural systems. PMID:23731073

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

PubMed

Bartolucci, Jorge; Verdugo, Fernando J; González, Paz L; Larrea, Ricardo E; Abarzua, Ema; Goset, Carlos; Rojo, Pamela; Palma, Ivan; Lamich, Ruben; Pedreros, Pablo A; Valdivia, Gloria; Lopez, Valentina M; Nazzal, Carolina; Alcayaga-Miranda, Francisca; Cuenca, Jimena; Brobeck, Matthew J; Patel, Amit N; Figueroa, Fernando E; Khoury, Maroun

2017-10-27

Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients. Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10 6 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography ( P =0.0167 versus baseline) and cardiac MRI ( P =0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P =0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class ( P =0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire ( P <0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy. Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs. URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777. © 2017 The Authors.

Combination of Azathioprine and Aminosalicylate Treatment Prevent Risk of Cardiovascular Disease in Women with Ulcerative Colitis by Reducing Inflammation.

PubMed

dos Santos, Lana Claudinez; Costa, Aline Villela; Lopes, Lorrayne Gonçalves; Leonel, Alda Jusceline; Aguilar, Edenil Costa; Noviello, Maria de Lourdes Meirelles; Ferrari, Maria de Lourdes de Abreu; Alvarez-Leite, Jacqueline I

2015-08-07

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with involvement of the immune system. Chronic inflammatory diseases have been associated with increased risk of cardiovascular disease (CVD) but few studies have assessed this risk in patients with UC and the influence of drug treatment. Thus, we evaluated the risk of development of CVD in women with UC in clinical remission, considering the drug treatment. Twenty-one women with UC participated in this study: 12 used aminosalicylates (ASA group) and 9 used azathioprine added to aminosalicylates (AZA+ASA group). The healthy control group was matched for age. We evaluated blood pressure, body composition, and biochemical and immunological parameters. Compared to the respective control group, the UC groups showed expansion of body fat and less lean body mass. Blood pressure, pro-inflammatory cytokines, nitric oxide, C reactive protein, erythrocyte sedimentation rate (ESR), and anti-oxidized LDL antibodies were higher in UC groups. Only AZA+ASA group showed increased anti-inflammatory cytokines (IL-10 and TGF-β). Framingham scores showed higher risk of CVD in UC groups. UC groups were compared and women treated with azathioprine showed reduction of total protein, globulin, ESR, and lymphocytes, with increased IL-6, TNF, IL-10, and TGF-β. Our data suggest that women with UC in clinical remission have a higher risk for development of atherosclerosis and CVD when compared to the control group, while women treated with azathioprine seem more protected than those treated only with aminosalicylates, due to better regulation of the inflammatory process.

Effects of indigo naturalis on colonic mucosal injuries and inflammation in rats with dextran sodium sulphate-induced ulcerative colitis.

PubMed

Wang, Yunliang; Liu, Lijuan; Guo, Yi; Mao, Tangyou; Shi, Rui; Li, Junxiang

2017-08-01

The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair.

Comparison of clinicopathologic characteristics of urothelial carcinoma between patients after renal transplantation and on dialysis.

PubMed

Zhang, Bo; Shen, Cheng; Han, Wen-ke; Yu, Wei

2014-09-15

Urothelial carcinoma (UC) is a common complication after renal replacement therapy (RRT) among Chinese end-stage renal disease (ESRD) patients. It is unclear whether there are any differences in the clinicopathologic characteristics of UC between renal transplantation (RT) and dialysis patients; such differences could impact RRT modality selection. We retrospectively reviewed clinicopathologic data for 27 RT patients and 40 dialysis patients who were diagnosed with UC in our center to explore differences in the clinicopathologic characteristics of UC and prognoses between the two groups. The median follow-up period was 92 months (2-137) for the RT group and 71 months (18-155) for the dialysis group. The demographic and baseline data showed no significant differences between the two groups. Upper urinary tract UC (UUC) occurred more frequently in the RT group (22 UUCs in 39 UCs), whereas bladder UC (BUC) predominated in the dialysis group (33 BUCs in 49 UCs) (P=0.025). The pathologic grading in the RT group was significantly higher than that in the dialysis group (P=0.046 for WHO1973 grading, P=0.026 for WHO2004 grading), whereas the difference in tumor stage was not significant (P=0.089). The RT group manifested a higher recurrence rate than the dialysis group (P=0.024). However, the overall and cancer-specific survival rates between the two groups were not significantly different (P=0.239 and P=0.818, respectively). Certain traits of UC, including tumor site, pathologic grading, and recurrence-free survival, were notably different between RT and dialysis patients, but the overall and cancer-specific survival rates were similar.

Moxibustion inhibits interleukin-12 and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis

PubMed Central

Wang, Xiao-Mei; Lu, Yuan; Wu, Lu-Yi; Yu, Shu-Guang; Zhao, Bai-Xiao; Hu, Hong-Yi; Wu, Huan-Gan; Bao, Chun-Hui; Liu, Hui-Rong; Wang, Jin-Hai; Yao, Yi; Hua, Xue-Gui; Guo, Hui-Ying; Shen, Li-Rong

2012-01-01

AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12). CONCLUSION: HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response. PMID:23239920

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

PubMed Central

Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

2018-01-01

Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating the microglial reaction in the peri-infarct cortex. PMID:29568282

[Effect of Electroacupuncture Stimulation of "Guanyuan" (CV 4) and "Zusanli" (ST 36) on Spleen Lymphocytes Treg/Th 17 Immune Balance in Ulcerative Colitis Mice].

PubMed

Wang, Cheng-yu-lin; Zeng, Lin-lan; Geng, Yu; Wang, Xiang; Zhang, He-jiao; Yang, Hui; Wu, Qiao- feng; Yu, Shu-guang

2016-02-01

To observe the effect of electroacupuncture (EA) intervention on spleen T-helper 17 (Th 17) and regulatory T (Treg) cell levels in mice with ulcerative colitis (UC), so as to reveal its mechanisms underlying improvement of UC. METHODS Kunming mice were randomized into control, UC model and EA groups, with 8 mice in each group. The UC model was established by giving the mice with 3% Dextran Sulfate Sodium (DSS) for 5 days. EA (15 Hz/25 Hz, 0.1-0.2 mA) was applied at "Guanyuan" (CV 4) and bilateral "Zusanli" (ST 36, used alternatively) for 10 min, once a day for 5 days. The animals' disease activity index [DAl, = (body weight index score + stool score + bleeding score)/3; 0-4 points] were calculated. The pathological changes of colon tissues were observed by light microscopy after H. E. stain, and spleen Treg (CD⁴⁺ CD²⁵⁺ Foxp³⁺ Treg) and Th 17 (CD³⁺ CD⁸⁺ IL-17⁺ Th 17) lymphocyte levels were determined by flow cytometry. Compared to the control group, the DAl score and the ratio of Th 17/CD⁸⁺ T cells were significantly increased, while the ratio of Treg/CD⁴⁺ T cells obviously decreased in the model group (P < 0.05). After EA intervention, the increased DAI score and the ratio of Th 17/CD⁸⁺ T cells and the decreased Treg/CD⁴⁺ T cells were reversed (P < 0.05), and the inflammatory cell infiltration degree of the colon tissue was attenuated. EA intervention can improve the, UC rats' symptoms of activity state, bloody or viscidity stool and colonic inflammation, probably by regulating the balance between the spleenic Treg and Th 17 lymphocytes.

Relationship between serum interleukin-17 level and inflammatory bowel disease.

PubMed

Liu, Q L; Huang, L; Zhao, Q J; Li, Q; He, Z

2016-01-01

By detecting expression of interleukin (IL)-17A, IL-10 and interferon-γ (IFN-γ) in serum of inflammatory bowel disease (IBD) patients, this study aims to analyze the effects of these factors on the pathogenesis of IBD. According to illness status, selected patients were divided into Crohn’s disease (CD) group (28 patients), ulcerative colitis (UC) group (74 patients) and normal control group (36 patients); enzymelinked immunosorbent assay (ELISA) was used to detect IL-17A, IL-10 and IFN-γ levels in serum; immunohistochemical assay was used to detect local IL-17A expression in the colonic mucosa of each group. Clinical results showed that IL-17A content of the UC group and CD group was significantly higher than that of the normal control group (p less than 0.05); IL-17A content of the CD group was higher than that of the UC group (p>0.05). The UC group had the highest IL-10 content, and the difference between the UC group and other two groups had statistical significance (p less than 0.05); the difference of IL-10 content between UC group and normal control group had no statistical significance (p>0.05). There was no significant difference of IFN-γ level between the CD group and the UC group and normal control group (p>0.05), and no significant difference of IFN-γ level was shown between the CD group and the UC group (p>0.05). Both the CD and UC groups showed IL-17A positive staining in cytoplasm of lymphocyte, however no positive staining was found in any layer of intestinal mucosa of the normal control group. IL-17A was locally expressed in the colon of IBD patients in remission; furthermore, it also had high expression in serum; thus, there still existed high expression of pro-inflammatory factor, which might be related to relapse of IBD. Therefore, prevention of IL-17A may become a feasible therapy for IBD in the future.

Effects of indigo naturalis on colonic mucosal injuries and inflammation in rats with dextran sodium sulphate-induced ulcerative colitis

PubMed Central

Wang, Yunliang; Liu, Lijuan; Guo, Yi; Mao, Tangyou; Shi, Rui; Li, Junxiang

2017-01-01

The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair. PMID:28781623

Comparison of ultra-congruent mobile- and fixed-bearing navigation-assisted total knee arthroplasty with minimum 5-year follow-up.

PubMed

Kim, Seong Hwan; Lim, Jung-Won; Ko, Young-Bong; Song, Min-Gu; Lee, Han-Jun

2016-11-01

The purpose of this study was to compare the midterm outcomes between fixed and mobile ultra-congruent (UC) bearings in total knee arthroplasty (TKA). This is a retrospective matched-pairs case-control study of patients who underwent primary navigation-assisted TKA with a minimum 5-year follow-up. A total of 182 cases involved the fixed UC bearing system as Group 1 and 101 cases involved mobile UC bearing system group as Group 2. After 1:1 matching, 73 knees in each group were enrolled. Clinical and radiographic outcomes were evaluated. The overall survival was 143 of 146 cases (97.9 %) at final follow-up, and 72 of 73 cases (96.3 %) in Group 1 and 71 of 73 cases (95.8 %) in Group 2 at final follow-up based on an endpoint of revision surgery. The reasons of revision TKA were periprosthetic fracture in Group 1, infection and bearing dislocation in Group 2. There was no statistical difference in Hospital for Special Surgery (HSS) scores, Knee Society Scores (KSS), WOMAC index score evaluations between groups. This study demonstrated that the fixed-bearing UC prosthesis could provide satisfactory performance compared with that of the mobile-bearing UC prosthesis with minimum 5-year follow-up. The fixed-bearing UC prosthesis could be considered in navigation-assisted TKA with theoretical advantages of UC design. IV.

Associations between STAT3 rs744166 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis.

PubMed

Zhang, Jixiang; Wu, Jianhong; Peng, Xiulan; Song, Jia; Wang, Jun; Dong, Weiguo

2014-01-01

Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11-1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). This meta-analysis indicates that carriers of the STAT3 rs744166 'A' allele have a significantly greater risk of CD and UC, especially among Caucasians.

Associations between STAT3 rs744166 Polymorphisms and Susceptibility to Ulcerative Colitis and Crohn's Disease: A Meta-Analysis

PubMed Central

Peng, Xiulan; Song, Jia; Wang, Jun; Dong, Weiguo

2014-01-01

Background Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. Materials and Methods Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. Results Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11–1.30, I 2 = 0%, P unadjusted<0.00001, P Bonferroni<0.00005, P FDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I 2 = 1%, P unadjusted = 0.001, P Bonferroni = 0.005, P FDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). Conclusion This meta-analysis indicates that carriers of the STAT3 rs744166 ‘A’ allele have a significantly greater risk of CD and UC, especially among Caucasians. PMID:25286337

Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

PubMed

Deparle, L A; Gupta, R C; Canerdy, T D; Goad, J T; D'Altilio, M; Bagchi, M; Bagchi, D

2005-08-01

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis.

PubMed

Zhu, Mingming; Xu, Xitao; Nie, Fang; Tong, Jinlu; Xiao, Shudong; Ran, Zhihua

2011-08-01

The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC. All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials. Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60-5.18) and remission rate (OR, 2.04; 95% CI, 1.36-3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44-31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22-29.90). The incidence of mild-moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04-0.60). Few severe adverse events were observed. Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

The UAS control segment architecture: an overview

NASA Astrophysics Data System (ADS)

Gregory, Douglas A.; Batavia, Parag; Coats, Mark; Allport, Chris; Jennings, Ann; Ernst, Richard

2013-05-01

The Under Secretary of Defense (Acquisition, Technology and Logistics) directed the Services in 2009 to jointly develop and demonstrate a common architecture for command and control of Department of Defense (DoD) Unmanned Aircraft Systems (UAS) Groups 2 through 5. The UAS Control Segment (UCS) Architecture is an architecture framework for specifying and designing the softwareintensive capabilities of current and emerging UCS systems in the DoD inventory. The UCS Architecture is based on Service Oriented Architecture (SOA) principles that will be adopted by each of the Services as a common basis for acquiring, integrating, and extending the capabilities of the UAS Control Segment. The UAS Task Force established the UCS Working Group to develop and support the UCS Architecture. The Working Group currently has over three hundred members, and is open to qualified representatives from DoD-approved defense contractors, academia, and the Government. The UCS Architecture is currently at Release 2.2, with Release 3.0 planned for July 2013. This paper discusses the current and planned elements of the UCS Architecture, and related activities of the UCS Community of Interest.

Reduced risk of UC in families affected by appendicitis: a Danish national cohort study.

PubMed

Nyboe Andersen, Nynne; Gørtz, Sanne; Frisch, Morten; Jess, Tine

2017-08-01

The possible aetiological link between appendicitis and UC remains unclear. In order to investigate the hereditary component of the association, we studied the risk of UC in family members of individuals with appendicitis. A cohort of 7.1 million individuals was established by linkage of national registers in Denmark with data on kinship and diagnoses of appendicitis and UC. Poisson regression models were used to calculate first hospital contact rate ratios (RR) for UC with 95% CIs between individuals with or without relatives with a history of appendicitis. During 174 million person-years of follow-up between 1977 and 2011, a total of 190 004 cohort members developed appendicitis and 45 202 developed UC. Individuals having a first-degree relative with appendicitis before age 20 years had significantly reduced risk of UC (RR 0.90; 95% CI 0.86 to 0.95); this association was stronger in individuals with a family predisposition to UC (RR 0.66; 95% CI 0.51 to 0.83). Individuals with a first-degree relative diagnosed with appendicitis before age 20 years are at reduced risk of UC, particularly when there is a family predisposition to UC. Our findings question a previously hypothesised direct protective influence of appendicitis on inflammation of the large bowel. Rather, genetic or environmental factors linked to an increased risk of appendicitis while being protective against UC may explain the repeatedly reported reduced relative risk of UC in individuals with a history of appendicitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?

PubMed

Balci, Ugur; Ozer, Kutan; Gorgel, Sacit Nuri; Sefik, Ertugrul; Girgin, Cengiz; Dincel, Cetin

2013-10-01

The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.

[Role of hippocampal neuronal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia].

PubMed

Ming, Hong; Chen, Rui; Wang, Jing; Ju, Jingmei; Sun, Li; Zhang, Guoxing

2014-12-01

To investigate the role of hippocampal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia. 45 ICR male mice were randomly divided into 3 groups: the unhandled control group (UC group, n = 15), the chronic intermittent hypoxia (CIH group, n = 15) and the pretreatment memantine group (MEM group, n = 15). CIH and MEM mice were subjected to intermittent hypoxia while UC mice to room air for 8 h per day during 4 weeks. Mice in the MEM group were pretreated with memantine (5 mg/kg) by intraperitoneal injection before the cycle started, and those in the UC group and the CIH group were treated with same volume of physiological saline. Neurobehavioral assessments were performed by Open filed and Morris water maze, [Ca²⁺]i in hippocampal neurons was evaluate by flow cytometry, and the expression of cleaved caspase-3, phospho-ERK1/2 in hippocampus were detected by Western blotting. Compared with the UC group, CIH mice displayed markedly more locomotor activity (P < 0.05) in Open filed test, longer mean escape latency (P < 0.05), less number of times of crossing the platform (P < 0.01) and less percentage of time in target quadrant (P < 0.01). Furthermore, exposure to CIH enhanced [Ca²⁺]i (vs. UC mice, 155 ± 12 vs. 92 ± 8, P < 0.01), and up-regulated the expression of cleaved caspase-3 (P < 0.01), but down-regulated the level of phospho-ERK1/2 (P < 0.05) in the hippocampus. Pre-treatment with memantine significantly decreased hyperlocomotion (P < 0.05), attenuated memory deficit (P < 0.05), mitigated [Ca²⁺]i (vs. CIH mice, 90 ± 8 vs. 155 ± 12, P < 0.01), decrease the expression of cleaved caspase-3 (P < 0.01), but increased the level of phospho-ERK1/2(P < 0.05) comparing to the CIH group. The neurobehavioral impairments induced by CIH are mediated, at least in part, by intracellular calcium concentration overload, neuron apoptosis, dephosphorylation of ERK1/2, which can be attenuated by memantine. Memantine may have a therapeutic effect in the neurocognitive impairment associated with OSAHS.

Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α

PubMed Central

Liu, Chang; Tang, Xiaojun; Feng, Ruihai; Yao, Genhong; Chen, Weiwei; Li, Wenchao; Liang, Jun; Feng, Xuebing

2018-01-01

Objective To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF-α in vitro to explore their effects on osteogenesis. Results The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF-α-treated CIA groups, compared with control mice (P < 0.001). Micro-CT showed that CIA mice developed osteoporosis at 12 weeks after immunization. The bone morphology parameters were partially improved in UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity (P < 0.001) and reduced mRNA and protein levels of osteogenic marker genes (P < 0.05) in CIA mice compared with DBA/1 mice. UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF-α level was decreased significantly in the UC-MSC group. The osteogenesis was reduced with the addition of TNF-α in vitro. Conclusion This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α. PMID:29853911

Professional charges not reimbursed to dentists in the U.S.: evidence from Medical Expenditure Panel Survey, 1996.

PubMed

Chattopadhyay, A; Slade, G D; Caplan, D J

2009-12-01

This cross-sectional study examined professional charges not paid to dentists. This analysis used logistic regression in SUDAAN examining the 1996 MEPS data from 12,931 adults. Among people incurring dental care charges, 13.6% had more than $50 of unpaid charge (UC). The percapita UC was $53.30. Total UC was higher for highest income group [45.4% of total] compared to lowest income group [26.0%]. The percapita UC of $76.70 for low income group was significantly greater than for high income group ($47.80, P < 0.01). More Medicaid recipients (52% vs. non-recipients: 12%) incurred at least $50 in UC (P < 0.01). Adjusted odds of incurring UC were greater for those employed (OR = 1.3, 95% CI: 1.0-1.7), and for those with private insurance (OR: 1.5, CI: 1.3-1.9). Number of dental procedure types modified the association between Medicaid recipient and UC (OR = 13.6 for Medicaid recipients undergoing multiple procedure types; OR: 2.3 for Medicaid non-recipients with multiple procedure types; OR: 1.9 for Medicaid recipients receiving single dental procedure. Having private insurance, being unemployed and being Medicaid insured undergoing multiple procedure were strongest predictors of UC.

Improving Work Outcomes of Dysthymia (Persistent Depressive Disorder) in an Employed Population

PubMed Central

Adler, David A.; Lerner, Debra; Visco, Zachary L.; Greenhill, Annabel; Chang, Hong; Cymerman, Elina; Azocar, Francisca; Rogers, William H.

2015-01-01

Objective To test the effectiveness of a work-focused intervention (WFI) on the work outcomes of employed adults with dysthymia. Method This subgroup analysis from a randomized controlled trial compares an initial sample of 167 employees (age ≥ 45 years), screened for dysthymia using the PC-SAD without current major depressive disorder randomized to WFI (n=85) or usual care (UC) (n=82). Study sites included 19 employers and five additional organizations. Telephone-based WFI counseling (eight, twice monthly 50-minute sessions) provided work coaching and modification, care coordination and cognitive-behavioral therapy (CBT). Adjusted mixed effects models compared the WFI versus UC group pre-intervention to four-month post-intervention change in at-work limitations measured by the Work Limitations Questionnaire. Secondary outcome analysis compared the change in self-reported absences and depression symptom severity (PHQ-9 scores). Results Work productivity loss scores improved 43.0% in the WFI group vs. 4.8% in UC (difference in change P < 0.001). Absence days declined by 58.3% in WFI vs. 0.0% in UC (difference in change P = .09). Mean PHQ-9 depression symptom severity declined 44.2% in WFI vs. 5.3% in UC (difference in change P < 0.001). Conclusion At four months, the WFI was more effective than UC on two of the three outcomes. It could be an important mental and functional health improvement resource for the employed dysthymic population. PMID:25892151

Improving work outcomes of dysthymia (persistent depressive disorder) in an employed population.

PubMed

Adler, David A; Lerner, Debra; Visco, Zachary L; Greenhill, Annabel; Chang, Hong; Cymerman, Elina; Azocar, Francisca; Rogers, William H

2015-01-01

To test the effectiveness of a work-focused intervention (WFI) on the work outcomes of employed adults with dysthymia. This subgroup analysis from a randomized controlled trial compares an initial sample of 167 employees (age: ≥45 years), screened for dysthymia using the PC-SAD without current major depressive disorder randomized to WFI (n=85) or usual care (UC) (n=82). Study sites included 19 employers and five additional organizations. Telephone-based WFI counseling (eight, twice monthly 50-min sessions) provided work coaching and modification, care coordination and cognitive behavioral therapy. Adjusted mixed effects models compared the WFI vs. UC group preintervention to 4-month postintervention change in at-work limitations measured by the Work Limitations Questionnaire. Secondary outcome analysis compared the change in self-reported absences and depression symptom severity (Patient Health Questionnaire PHQ-9 scores). Work productivity loss scores improved 43.0% in the WFI group vs. 4.8% in UC (difference in change: P<.001). Absence days declined by 58.3% in WFI vs. 0.0% in UC (difference in change: P=.09). Mean PHQ-9 depression symptom severity declined 44.2% in WFI vs. 5.3% in UC (difference in change: P<.001). At 4 months, the WFI was more effective than UC on two of the three outcomes. It could be an important mental and functional health improvement resource for the employed dysthymic population. Copyright © 2015 Elsevier Inc. All rights reserved.

Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners.

PubMed

Bennett, A L; Buckton, S; Lawrance, I; Leong, R W; Moore, G; Andrews, J M

2015-12-01

Current models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non-specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed. © 2015 Royal Australasian College of Physicians.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.

PubMed

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-10-01

Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[Clinical analysis of cutaneous manifestations and related factors in patients with ulcerative colitis].

PubMed

Tian, Y; Li, J X; Wang, H H; Li, R Y; Liu, X G

2016-07-01

To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors. Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study. Skin disorders were confirmed by the dermatologists. Clinical data were collected and compared between patients with and without cutaneous manifestations. Among the total 373 UC patients, there were 34 cases (9.1%) with cutaneous manifestations, including 11 pyoderma gangrenosum, 8 erythema nodosum, 6 eczema, 3 psoriasis, 2 pemphigus, 1 granulomatous cheilitis, 1 ichthyosis, 1 acne rosacea, and 1 impetigo. The skin manifestations may occur after the diagnosis, simultaneously or even before the diagnosis of UC, which were 24, 7 and 3 patients respectively. The mean age in patients with skin lesions was (47.2±12.1) years, male to female ratio 0.79∶1. More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0%(17/34) vs 25.1%(85/339), P=0.01]. In addition, the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5%(26/34) vs 54.6%(185/339), P=0.04]. The cutaneous manifestations associated with UC are polymorphic, erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients. Skin lesions occur concurrently, pre or post the diagnosis of UC. Skin lesions in UC patients suggest more severe disease activity. Clinicians need to pay more attention to this group.

Exploring Productivity Outcomes from a Brief Intervention for At-Risk Drinking in an Employee Assistance Program

PubMed Central

Osilla, Karen Chan; Cruz, Erin dela; Miles, Jeremy N.V.; Zellmer, Steven; Watkins, Katherine; Larimer, Mary E.; Marlatt, G. Alan

2009-01-01

Brief intervention (BI) research has traditionally examined alcohol and drug use outcomes; however it is unknown whether BIs can also impact on-the-job productivity. This exploratory study examines changes in workplace productivity and related costs for clients receiving a BI for at-risk drinking in the employee assistance program (EAP). Participants were 44 clients attending the EAP for behavioral health concerns, screened for at-risk drinking, assigned to BI+Usual Care (n=25) or UC alone (n=19), and who completed 3-month follow-up. Absenteeism, presenteeism, and productivity costs were derived as outcomes. At follow-up, participants in the BI+UC group had improved productivity when at work (presenteeism) compared to the UC group. The estimated cost savings from improved productivity for the BI+UC group was $1200 per client over the UC group. Groups did not differ by absenteeism (missed days of work). Preliminary evidence suggests the broad impact BIs may have. Implications for future BI research are discussed. PMID:19897312

A randomised translational trial of lifestyle intervention using a 3-tier shared care approach on pregnancy outcomes in Chinese women with gestational diabetes mellitus but without diabetes.

PubMed

Yang, Xilin; Tian, Huiguang; Zhang, Fuxia; Zhang, Cuiping; Li, Yi; Leng, Junhong; Wang, Leishen; Liu, Gongshu; Liu, Gongsu; Dong, Ling; Yu, Zhijie; Hu, Gang; Chan, Juliana Cn

2014-10-28

There are no randomised controlled trials to demonstrate whether lifestyle modifications can improve pregnancy outcomes of gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group's (IADPSG) criteria. We tested the effectiveness of lifestyle modifications implemented in a 3-tier's shared care (SC) on pregnancy outcomes of GDM. Between December 2010 and October 2012, we randomly assigned 700 women with IADPSG-defined GDM but without diabetes at 26.3 (interquartile range: 25.4-27.3) gestational weeks in Tianjin, China, to receive SC or usual care (UC). The SC group received individual consultations and group sessions and performed regular self-monitoring of blood glucose compared to one hospital-based education session in the UC group. The outcomes were macrosomia defined as birth weight ≥ 4.0 kg and the pregnancy-induced hypertension (PIH). Women in the SC (n = 339) and UC (n = 361) groups delivered their infants at similar gestational weeks. Birth weight of infants in the SC group was lower than that in the UC group (3469 vs. 3371 grams, P = 0.021). The rate of macrosomia was 11.2% (38/339) in the SC group compared to 17.5% (63/361) in the UC group with relative risk (RR) of 0.64 (95% CI: 0.44-0.93). The rate of PIH was 8.0% (27/339) in the SC compared to 4.4% (16/361) in the UC with RR of 1.80 (0.99-3.28). Apgar score at 1 min < 7 was lower but preeclampsia was higher in the SC than in the UC. Lifestyle modifications using a SC system improved pregnancy outcomes in Chinese women with GDM. Clinicaltrials.gov; NCT01565564.

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults

PubMed Central

Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina

2017-01-01

Background Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods One hundred seven frail, obese older adults were randomized into the control (N = 27), diet (N = 26), exercise (N = 26), and diet-exercise (N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). Results UcOC increased in the diet group (36 ± 11.6%) but not in the other groups (P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months (P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only (R2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2 = 0.140 and 0.107) and diet-exercise (∆R2 = 0.427 and 0.243) groups (P < 0.05 for all). Conclusions Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107. PMID:28951766

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.

PubMed

Colleluori, Georgia; Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina; Villareal, Dennis T

2017-01-01

Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. One hundred seven frail, obese older adults were randomized into the control ( N = 27), diet ( N = 26), exercise ( N = 26), and diet-exercise ( N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). UcOC increased in the diet group (36 ± 11.6%) but not in the other groups ( P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months ( P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only ( R 2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆ R 2 = 0.140 and 0.107) and diet-exercise (∆ R 2 = 0.427 and 0.243) groups ( P < 0.05 for all). Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

Randomized Trial of Family Therapy versus Non-Family Treatment for Adolescent Behavior Problems in Usual Care

PubMed Central

Hogue, Aaron; Dauber, Sarah; Henderson, Craig E.; Bobek, Molly; Johnson, Candace; Lichvar, Emily; Morgenstern, Jon

2014-01-01

Objective A major focus of implementation science is discovering whether evidence-based approaches can be delivered with fidelity and potency in routine practice. This randomized trial compared usual care family therapy (UC-FT), implemented without a treatment manual or extramural support as the standard-of-care approach in a community clinic, to non-family treatment (UC-Other) for adolescent conduct and substance use disorders. Method The study recruited 205 adolescents (mean age 15.7 years; 52% male; 59% Hispanic American, 21% African American) from a community referral network, enrolling 63% for primary mental health problems and 37% for primary substance use problems. Clients were randomly assigned to either the UC-FT site or one of five UC-Other sites. Implementation data confirmed that UC-FT showed adherence to the family therapy approach and differentiation from UC-Other. Follow-ups were completed at 3, 6, and 12 months post-baseline. Results There was no between-group difference in treatment attendance. Both conditions demonstrated improvements in externalizing, internalizing, and delinquency symptoms. However, UC-FT produced greater reductions in youth-reported externalizing and internalizing among the whole sample, in delinquency among substance-using youth, and in alcohol and drug use among substance-using youth. The degree to which UC-FT outperformed UC-Other was consistent with effect sizes from controlled trials of manualized family therapy models. Conclusions Non-manualized family therapy can be effective for adolescent behavior problems within diverse populations in usual care, and it may be superior to non-family alternatives. PMID:25496283

Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn’s Colitides

PubMed Central

Korolkova, Olga Y; Myers, Jeremy N; Pellom, Samuel T; Wang, Li; M’Koma, Amosy E

2015-01-01

BACKGROUND As accessible diagnostic approaches fail to differentiate between ulcerative colitis (UC) and Crohn’s colitis (CC) in one-third of patients with predominantly colonic inflammatory bowel disease (IBD), leading to inappropriate therapy, we aim to investigate the serum cytokine levels in these patients in search of molecular biometric markers delineating UC from CC. METHODS We measured 38 cytokines, chemokines, and growth factors using magnetic-bead-based multiplex immunoassay in 25 UC patients, 28 CC patients, and 30 controls. Our results are compared with those from a review of current literature regarding advances in serum cytokine profiles and associated challenges preventing their use for diagnostic/prognostic purposes. RESULTS Univariate analysis showed statistically significant increases of eotaxin, GRO, and TNF-α in UC patients compared to controls (Ctrl); interferon γ, interleukin (IL)-6, and IL-7 in CC group compared to Ctrl; and IL-8 in both UC and CC versus Ctrl. No cytokines were found to be different between UC and CC. A generalized linear model identified combinations of cytokines, allowing the identification of UC and CC patients, with area under the curve (AUC) = 0.936, as determined with receiver operating characteristic (ROC) analysis. CONCLUSIONS The current knowledge available about circulating cytokines in IBD is often contradictory. The development of an evidence-based tool using cytokines for diagnostic accuracy is still preliminary. PMID:26078592

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

PubMed

Bauer, Victoria; Goodman, Nancy; Lapin, Brittany; Cooley, Camille; Wang, Ed; Craig, Terri L; Glosner, Scott E; Juhn, Mark S; Cappelleri, Joseph C; Sadosky, Alesia B; Masi, Christopher

2018-06-01

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

Exploring productivity outcomes from a brief intervention for at-risk drinking in an employee assistance program.

PubMed

Osilla, Karen Chan; dela Cruz, Erin; Miles, Jeremy N V; Zellmer, Steven; Watkins, Katherine; Larimer, Mary E; Marlatt, G Alan

2010-03-01

Brief intervention (BI) research has traditionally examined alcohol and drug use outcomes; however it is unknown whether BIs can also impact on-the-job productivity. This exploratory study examines changes in workplace productivity and related costs for clients receiving a BI for at-risk drinking in the employee assistance program (EAP). Participants were 44 clients attending the EAP for behavioral health concerns, screened for at-risk drinking, assigned to BI+Usual Care (n=25) or UC alone (n=19), and who completed 3-month follow-up. Absenteeism, presenteeism, and productivity costs were derived as outcomes. At follow-up, participants in the BI+UC group had improved productivity when at work (presenteeism) compared to the UC group. The estimated cost savings from improved productivity for the BI+UC group was $1200 per client over the UC group. Groups did not differ by absenteeism (missed days of work). Preliminary evidence suggests the broad impact BIs may have. Implications for future BI research are discussed. Copyright 2009 Elsevier Ltd. All rights reserved.

Effect of a Food Supplement Containing L-Methionine on Urinary Tract Infections in Pregnancy: A Prospective, Multicenter Observational Study.

PubMed

Passaro, Mario; Mainini, Giampaolo; Ambrosio, Francesco; Sgambato, Raimondo; Balbi, Giancarlo

2017-06-01

Adjuvants or alternatives to antibiotics in urinary tract infections (UTIs) during pregnancy seem advisable because of possible fetal stress. The present study assessed the effectiveness of a food supplement containing L-methionine and Hibiscus sabdariffa L. and Boswellia serrata Roxb. extracts as a treatment for symptomatic UTIs in pregnancy. Pregnant patients with symptomatic cystitis were screened for UTIs in three different clinical centers. Those unwilling to take antibiotics were offered two alternative treatments: (A) a 1-week treatment with the food supplement or (B) a week in which they were advised to increase their fluid consumption to more than 1.5 L daily. After 1 week, group B patients who still had positive urine cultures (UCs) or had no UC performed took the food supplement for an additional week. UCs were performed on all patients at the first visit (w0) and on most of them at 7 days (w1). Patients who were still positive at w1 or had no UC performed at w1 had UC performed 14 days (w2) thereafter. Of 264 pregnant women enrolled, 216 joined group A, while 48 joined group B. At w1, 70.0% of group A patients and 43.2% of those in group B had negative UCs (p = 0.003). The reduction of bacterial load was 42.2% ± 8.0% and 4.5% ± 9.2%, respectively (p < 0.0001). At w1, symptoms disappeared in 135 patients (62.5%) in group A and 22 patients (45.8%) in group B (p = 0.03). At w2, 30 of 32 group B patients who switched to taking the supplement for the second week had negative UCs, including 20 who had been positive at w1. At w2, all group A patients had negative UCs. No side effects were reported. The food supplement provided effective treatment and might be an adjuvant or alternative to antibiotic therapy of symptomatic UTI in pregnancy.

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

PubMed Central

Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying

2016-01-01

Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton’s jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC-MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM-DiI-labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Significance Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called “no-option” patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation. PMID:27334487

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia.

PubMed

Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying; Lü, Shuang-Hong; Zhang, Xiao-Zhong

2016-08-01

: Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton's jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC-MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM-DiI-labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called "no-option" patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation. ©AlphaMed Press.

Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

PubMed

Tsai, Hsin-Lin; Chang, Jei-Wen; Wu, Tsai-Hun; King, Kuang-Liang; Yang, Ling-Yu; Chan, Yu-Jiun; Yang, An-Hang; Chang, Fu-Pang; Pan, Chin-Chen; Yang, Wu-Chang; Loong, Che-Chuan

2014-07-15

To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

Fabrication and modeling of electrochemical double-layer capacitors using carbon nano-onion electrode structures

NASA Astrophysics Data System (ADS)

Parigi, Fabio

Electrochemical capacitors or ultracapacitors (UCs) that are commercially available today overcome battery limitations in terms of charging time (from tens of minutes to seconds) and limited lifetime (from a few thousand cycles up to more than one million) but still lack specific energy and energy density (2-5% of a lithium ion battery). The latest innovations in carbon nanomaterials, such as carbon nanotubes as an active electrode material for UCs, can provide up to five times as much energy and deliver up to seven times more power than today's activated carbon electrodes. Further improvements in UC power density have been achieved by using state-of-the-art carbon nano-onions (CNOs) for ultracapacitor electrodes. CNO UCs could exhibit up to five times the power density of single-wall CNT UCs and could substantially contribute to reducing the size of an energy storage system as well as the volume and weight, thus improving device performance. This dissertation describes the fabrication of CNO electrodes as part of an UC device, the measurement and analysis of the new electrode's performance as an energy storage component, and development of a new circuit model that accurately describes the CNO UC electrical behavior. The novel model is based on the impedance spectra of CNO UCs and cyclic voltammetry measurements. Further, the model was validated using experimental data and simulation. My original contributions are the fabrication process for reliable and repeatable electrode fabrication and the modeling of a carbon nano-onion ultracapacitor. The carbon nano-onion ultracapacitor model, composed of a resistor, an inductor, a capacitor (RLC), and a constant phase element (CPE), was developed along with a parameter extraction procedure for the benefit of other users. The new model developed, proved to be more accurate than previously reported UC models.

Umbilical cord mesenchymal stromal cell transplantations: A systemic analysis of clinical trials.

PubMed

Can, Alp; Celikkan, Ferda Topal; Cinar, Ozgur

2017-12-01

The advances and success of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in experimental disease animal models have fueled the development of targeted therapies in humans. The therapeutic potential of allogeneic transplantation of UC-MSCs has been under examination since 2009. The purpose of this systematic analysis was to review the published results, limitations and obstacles for UC-MSC transplantation. An extensive search strategy was applied to the published literature, 93 peer-reviewed full-text articles and abstracts were found published by early August 2017 that investigated the safety, efficacy and feasibility of UC-MSCs in 2001 patients with 53 distinct pathologies including many systemic/local, acute/chronic conditions. Few data were extracted from the abstracts and/or Chinese-written articles (n = 7, 8%). Importantly, no long-term adverse effects, tumor formation or cell rejection were reported. All studies noted certain degrees of therapeutic benefit as evidenced by clinical symptoms and/or laboratory findings. Thirty-seven percent (n = 34) of studies were found published as a single case (n = 10; 11%) or 2-10 case reports (n = 24; 26%) with no control group. Due to the nature of many stem cell-based studies, the majority of patients also received conventional therapy regimens, which obscured the pure efficacy of the cells transplanted. Randomized, blind, phase 1/2 trials with control groups (placebo-controlled) showed more plausible results. Given that most UC-MSC trials are early phase, the internationally recognized cell isolation and preparation standards should be extended to future phase 2/3 trials to reach more convincing conclusions regarding the safety and efficacy of UC-MSC therapies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Relationship and significance between anti-β2-glycoproteinI antibodies and platelet activation state in patients with ulcerative colitis

PubMed Central

Gao, Yan-Hang; Gao, Pu-Jun; Wang, Chun-Guang; Wang, Xiao-Cong; Piao, Yun-Feng

2008-01-01

AIM: To study the relationship between anti-β2-glycoprotein I (aβ2GPI) antibodies and platelet activation state in patients with ulcerative colitis (UC) and its significance. METHODS: Peripheral blood samples were collected from 56 UC patients (34 males and 22 females, aged 43.5 years, range 21-66 years), including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GPI was measured by ELISA. The platelet activation markers, platelet activation complex-I (PAC-I) and P-selectin (CD62P) were detected by flow cytometry. RESULTS: The A value for IgG aβ2GPI in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups (0.50 ± 0.13 and 0.22 ± 0.14, P < 0.01). There was a significant difference between the two groups (P < 0.01). The A value for IgM aβ2GPI in the active and remittent UC groups was 0.43 ± 0.13 and 0.38 ± 0.12, significantly higher than that in the control group (0.20 ± 0.12, P < 0.01). However, there was no significant difference between the two groups (P > 0.05). The PAC-I positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group (6.3% ± 1.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). The CD62P positive rate for the active and remittent UC groups was 45.0% ± 8.8% and 31.9% ± 7.8% respectively, significantly higher than that for the control group (9.2% ± 2.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). In the active UC group, the more severe the state of illness was, the higher the A value for IgG aβ2GPI was, and the positive rate for PAC-I and CD62P was positively correlated with the state of illness (Faβ2GPI = 3.679, P < 0.05; FPAC-I (%) = 5.346, P < 0.01; and FCD62P (%) = 5. 418, P < 0.01). Meanwhile, in the same state of illness, the A value for IgG aβ2GPI was positively correlated to the positive rates for PAC-I and CD62P. CONCLUSION: aβ2GPI level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC. PMID:18205270

Relationship and significance between anti-beta2-glycoprotein I antibodies and platelet activation state in patients with ulcerative colitis.

PubMed

Gao, Yan-Hang; Gao, Pu-Jun; Wang, Chun-Guang; Wang, Xiao-Cong; Piao, Yun-Feng

2008-02-07

To study the relationship between anti-beta2-glycoprotein I (abeta2GPI) antibodies and platelet activation state in patients with ulcerative colitis (UC) and its significance. Peripheral blood samples were collected from 56 UC patients (34 males and 22 females, aged 43.5 years, range 21-66 years), including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of abeta2GPI was measured by ELISA. The platelet activation markers, platelet activation complex-I (PAC-I) and P-selectin (CD62P) were detected by flow cytometry. The A value for IgG abeta2GPI in the active UC group was 0.61 +/- 0.13, significantly higher than that in the remittent UC and control groups (0.50 +/- 0.13 and 0.22 +/- 0.14, P < 0.01). There was a significant difference between the two groups (P < 0.01). The A value for IgM abeta2GPI in the active and remittent UC groups was 0.43 +/- 0.13 and 0.38 +/- 0.12, significantly higher than that in the control group (0.20 +/- 0.12, P < 0.01). However, there was no significant difference between the two groups (P > 0.05). The PAC-I positive rate for the active and remittent UC groups was 30.6% +/- 7.6% and 19.6% +/- 7.8% respectively, significantly higher than that for the control group (6.3% +/- 1.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). The CD62P positive rate for the active and remittent UC groups was 45.0% +/- 8.8% and 31.9% +/- 7.8% respectively, significantly higher than that for the control group (9.2% +/- 2.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). In the active UC group, the more severe the state of illness was, the higher the A value for IgG abeta2GPI was, and the positive rate for PAC-I and CD62P was positively correlated with the state of illness (Fabeta2GPI = 3.679, P < 0.05; FPAC-I (%) = 5.346, P < 0.01; and FCD62P (%) = 5. 418, P < 0.01). Meanwhile, in the same state of illness, the A value for IgG abeta2GPI was positively correlated to the positive rates for PAC-I and CD62P. abeta2GPI level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC.

Appendectomy, smoking habits and the risk of developing ulcerative colitis: a case control study in private practice setting.

PubMed

de Saussure, Philippe; Clerson, Pierre; Prost, Pierre-Louis; Truong Tan, Nghiep; Bouhnik, Yoram; Gil-Rch

2007-05-01

The strongest environmental factors identified for ulcerative colitis (UC) are cigarette smoking and appendectomy. However, most studies have been performed using case-controls from hospital-based populations. The purpose of this study was to compare the history of previous appendectomy and smoking habits in a group of patients with UC and a control group, followed by gastroenterologists in private practice. We performed a case control study in which 100 physicians recruited UC-patients and age and sex matched controls. Data were collected during a single visit. Based on a standardized questionnaire, UC patients and controls were divided into never, former or current smokers, and into subjects with or without a previous history of appendectomy. One hundred and ninety eight age- and sex-matched pairs of UC patients and controls were included. The prevalence of appendectomy in the UC-patients and control group was 12% and 46%, respectively. The pairwise-matched OR of ulcerative colitis for previous appendectomy was 0.10 (95% CI, 0.05-0.21) (P<0.0001). The OR for former and never smokers versus current smokers was 2.40 (95% CI 1.31-4.38) (P=0.004). In UC-patients, the OR of family history of UC compared with controls was 2.80 (95% CI, 1.01-7.77) (P=0.048). This case-control study confirmed a strong negative correlation between both appendectomy and tobacco smoking, and ulcerative colitis in patients followed-up by gastroenterological practitioners.

A 24-week randomised controlled trial comparing usual care and metabolic-based diet plans in obese adults.

PubMed

McDoniel, S O; Hammond, R S

2010-10-01

Usual care (UC) practice for weight management often includes providing standardised, ad libitum, low-calorie nutrition plans. However, weight loss using such plans appears comparable with metabolic-based diet (MD) plans that are closer to resting energy expenditure (REE) level. In addition, MD plans are approximately 250-750 kcal/day higher in caloric values compared with UC plans. Therefore, the purpose of this study was to compare weight loss and eating behaviour differences between UC and MD plans. Seventy-four obese (30.0-51.7 kg/m(2) ) adults (21-67 years) voluntarily participated in a 24-week randomised study. UC men and women received a fixed, ad libitum, 1600 and 1200 kcal/day nutrient plan, respectively. MD participants received an individualised treatment plan based from measured REE. Bodyweight and eating behaviours (i.e. intake, restraint and uncontrolled eating) were assessed over time. Intent-to-treat analysis indicated no significant difference in weight loss (UC: -5.7 ± 6.3% vs. MD: -5.3 ± 7.1% p = 0.67) between groups over time. There was no difference in daily energy intake (UC: 2490 ± 576 kcal/day vs. MD: 2525 ± 475 kcal/day) at 24 weeks between groups. Both groups experienced a significant improvement (p < 0.05) in eating dietary restraint and uncontrolled eating yet there was no difference between groups. From this study, UC calorie plans do not generate more weight loss or improve eating behaviours in comparison with MD calorie plans. As treatment effects are comparable, clinicians can select UC or MD plan options based on clinician and patient preference. © 2010 Blackwell Publishing Ltd.

Suprapubic tube versus urethral catheter drainage after robot-assisted radical prostatectomy: a systematic review and meta-analysis.

PubMed

Jian, Zhongyu; Feng, Shijian; Chen, Yuntian; Wei, Xin; Luo, Deyi; Li, Hong; Wang, Kunjie

2018-01-05

Prostate cancer is one of the most common cancers in the elderly population. The standard treatment is radical prostatectomy (RARP). However, urologists do not have consents on the postoperative urine drainage management (suprapubic tube (ST)/ urethral catheter (UC)). Thus, we try to compare ST drainage to UC drainage after robot-assisted radical prostatectomy regarding to comfort, recovery rate and continence using the method of meta-analysis. A systematic search was performed in Dec. 2017 on PubMed, Medline, Embase and Cochrane Library databases. The authors independently reviewed the records to identify studies comparing ST with UC of patients underwent RARP. Meta-analysis was performed using the extracted data from the selected studies. Seven studies, including 3 RCTs, with a total of 946 patients met the inclusion criteria and were included in our meta-analysis. Though there was no significant difference between the ST group and the UC group on postoperative pain (RR1.73, P 0.20), our study showed a significant improvement on bother or discomfort, defined as trouble in hygiene and sleep, caused by catheter when compared two groups at postoperative day (POD) 7 in ST group (RR2.05, P 0.006). There was no significant difference between the ST group and UC group on urinary continence (RR0.98, P 0.74) and emergency department visit (RR0.61, P 0.11). The rates of bladder neck contracture and other complications were very low in both groups. Compared to UC, ST showed a weak advantage. So it might be a good choice to choose ST over RARP.

Enterohepatic helicobacter in ulcerative colitis: potential pathogenic entities?

PubMed

Thomson, John M; Hansen, Richard; Berry, Susan H; Hope, Mairi E; Murray, Graeme I; Mukhopadhya, Indrani; McLean, Mairi H; Shen, Zeli; Fox, James G; El-Omar, Emad; Hold, Georgina L

2011-02-23

Changes in bacterial populations termed "dysbiosis" are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC. A dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p<0.0001). PCR and FISH results were concordant in 74 (67.9%) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR. Helicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable interrogation of pathogenicity against established criteria.

Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin

Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted intomore » the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.« less

Biological effects of low-level laser irradiation on umbilical cord mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Chen, Hongli; Wang, Hong; Li, Yingxin; Liu, Weichao; Wang, Chao; Chen, Zhuying

2016-04-01

Low-level laser irradiation (LLLI) can enhance stem cell (SC) activity by increasing migration and proliferation. This study investigated the effects of LLLI on proliferation, enzymatic activity, and growth factor production in human umbilical cord mesenchymal SCs (hUC-MSCs) as well as the underlying mechanisms. hUC-MSCs were assigned to a control group (non-irradiation group) and three LLLI treatment groups (635 nm group, 808 nm group, and 635/808 nm group). Laser power density and energy density of 20 mW/cm2 and 12 J/cm2, respectively, were used for each experiment. The proliferation rate was higher in the 635 nm as compared to the other groups. LLLI at 808 nm did not induce cell proliferation. ROS levels in cells exposed to 635, 808, and 635/808 nm radiation were increased by 52.81%, 26.89%, and 21.15%, respectively, relative to the control group. CAT, tGPx, and SOD activity was increased. LLLI at 808 nm increased the levels of IL-1, IL-6, and NFκB but not VEGF. LLLI improved hUC-MSCs function and increased antioxidant activity. Dual-wavelength LLLI had more potent effects on hUC-MSCs than single-wavelength treatment. LLLI has potential applications in the preconditioning of hUC-MSCs in vitro prior to transplantation, which could improve the regenerative capacity of cells.

Biological effects of low-level laser irradiation on umbilical cord mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Hongli; Wang, Hong; Li, Yingxin, E-mail: yingxinli2005@126.com

2016-04-15

Low-level laser irradiation (LLLI) can enhance stem cell (SC) activity by increasing migration and proliferation. This study investigated the effects of LLLI on proliferation, enzymatic activity, and growth factor production in human umbilical cord mesenchymal SCs (hUC-MSCs) as well as the underlying mechanisms. hUC-MSCs were assigned to a control group (non-irradiation group) and three LLLI treatment groups (635 nm group, 808 nm group, and 635/808 nm group). Laser power density and energy density of 20 mW/cm{sup 2} and 12 J/cm{sup 2}, respectively, were used for each experiment. The proliferation rate was higher in the 635 nm as compared to themore » other groups. LLLI at 808 nm did not induce cell proliferation. ROS levels in cells exposed to 635, 808, and 635/808 nm radiation were increased by 52.81%, 26.89%, and 21.15%, respectively, relative to the control group. CAT, tGPx, and SOD activity was increased. LLLI at 808 nm increased the levels of IL-1, IL-6, and NFκB but not VEGF. LLLI improved hUC-MSCs function and increased antioxidant activity. Dual-wavelength LLLI had more potent effects on hUC-MSCs than single-wavelength treatment. LLLI has potential applications in the preconditioning of hUC-MSCs in vitro prior to transplantation, which could improve the regenerative capacity of cells.« less

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis.

PubMed

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-10-27

Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. © European Crohn’s and Colitis Organisation (ECCO) 2017.

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis

PubMed Central

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-01-01

Abstract Background and Aims Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Methods Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Results Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Conclusions Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. PMID:28981629

Evaluation of a multiplex PCR assay for detection of cytomegalovirus in stool samples from patients with ulcerative colitis

PubMed Central

Nahar, Saifun; Iraha, Atsushi; Hokama, Akira; Uehara, Ayako; Parrott, Gretchen; Ohira, Tetsuya; Kaida, Masatoshi; Kinjo, Tetsu; Kinjo, Takeshi; Hirata, Tetsuo; Kinjo, Nagisa; Fujita, Jiro

2015-01-01

AIM: To evaluate a multiplex PCR assay for the detection of bacterial and viral enteropathogens in stool samples from patients with ulcerative colitis (UC). METHODS: We prospectively analyzed 300 individuals, including immunocompetent patients, immunocompromised patients, and patients with UC. Stool samples were collected from the recto-sigmoid region of the colon by endoscopy. The samples were qualitatively analyzed for bacterial and viral enteropathogens with a multiplex PCR assay using a Seeplex® Kit. Additional clinical and laboratory data were collected from the medical records. RESULTS: A multiplex PCR assay detected 397 pathogens (191 bacteria and 206 viruses) in 215 samples (71.7%). The most frequently detected bacteria were Escherichia coli H7, 85 (28.3%); followed by Aeromonas spp., 43 (14.3%); and Clostridium perfringens, 36 (12.0%) samples. The most prevalent viruses were Epstein-Barr virus (EBV), 90 (30.0%); followed by human herpes virus-6 (HHV-6), 53 (17.7%); and cytomegalovirus (CMV), 37 (12.3%) samples. The prevalence rate of CMV infection was significantly higher in the immunocompromised group than in the immunocompetent group (P < 0.01). CMV infection was more common in patients with UC (26/71; 36.6%) than in the immunocompetent patients excluding UC (6/188; 3.2%) (P < 0.01). CMV infection was more prevalent in UC active patients (25/58; 43.1%) than in UC inactive patients (1/13; 7.7%) (P < 0.05). Among 4 groups which defined by the UC activity and immunosuppressive drugs, the prevalence rate of CMV infection was highest in the UC active patients with immunosuppressive drugs (19/34; 55.8%). Epstein-Barr virus (EBV) infection was more common in the immunocompromised patients excluding UC (18/41; 43.9%) than in the immunocompetent patients excluding UC (47/188; 25.0%) (P < 0.05). The simultaneous presence of CMV and EBV and/or HHV6 in UC active patients (14/58; 24.1%) was greater than in immunocompromised patients excluding UC (5/41; 12.2%) (P < 0.05). CONCLUSION: The multiplex PCR assay that was used to analyze the stool samples in this study may serve as a non-invasive approach that can be used to exclude the possibility of CMV infection in patients with active UC who are treated with immunosuppressive therapy. PMID:26640344

Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat.

PubMed

Wu, Wen-Jin; Yan, Ru; Li, Ting; Li, Ya-Ping; Zhou, Rui-Na; Wang, Yi-Tao

2017-02-23

Rhubarb (Rhei Rhizoma et Radix) is used for the treatment of digestive diseases in traditional medicinal practice in China. Recent studies also support its beneficial activities in alleviating ulcerative colitis (UC). This study aimed to characterize the oral pharmacokinetics of rhubarb anthraquinones, the main bioactive components of this herb, in the experimental chronic colitis rat model induced by dextran sulfate sodium (DSS) and to identify the factors causing the pharmacokinetic alterations. Rats received drinking water (normal group) or 5% DSS for the first 7 days and 3% DSS for additional 14 days (UC group). On day 21 both groups received an oral dose of the rhubarb extract (equivalent to 5.0g crude drug/kg body weight). Plasma anthraquinone aglycones levels were determined directly by an LC-MS/MS method and the total of each anthraquinone (aglycone+conjugates) was quantified after β-glucuronidases hydrolysis. Rhubarb anthraquinones predominantly existed as conjugates in plasma samples from both groups and only free aloe-emodin, rhein and emodin were detected. Compared to the normal rats, both C max and AUC of the three free anthraquinones were increased, while the systemic exposure (AUC) of the total (aglycone+conjugates) of most anthraquinones decreased by UC accompanied by the disappearance of multiple-peak phenomenon in the plasma concentration-time profiles. Gut bacteria from UC rats exhibited a decreased activity in hydrolyzing anthraquinone glycosides to form respective aglycone and there were significant decreases in microbial β-glucosidases and β-glucuronidases activities. Moreover, the intestinal microsomes from UC rats catalyzed glucuronidation of free anthraquinones with higher activities, while the activities of hepatic microsomes were comparable to normal rats. The decreases of β-glucuronidases activity in DSS-induced chronic rat colitis should mainly account for the decreases in systemic exposure and abrogation of enterohepatic recirculation of most rhubarb anthraquinones after oral intake. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq.

PubMed

Maeda, Shingo; Tomiyasu, Hirotaka; Tsuboi, Masaya; Inoue, Akiko; Ishihara, Genki; Uchikai, Takao; Chambers, James K; Uchida, Kazuyuki; Yonezawa, Tomohiro; Matsuki, Naoaki

2018-04-27

Invasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC. Total RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks. Differential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E 2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property. Our data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC.

A three-stage birandom program for unit commitment with wind power uncertainty.

PubMed

Zhang, Na; Li, Weidong; Liu, Rao; Lv, Quan; Sun, Liang

2014-01-01

The integration of large-scale wind power adds a significant uncertainty to power system planning and operating. The wind forecast error is decreased with the forecast horizon, particularly when it is from one day to several hours ahead. Integrating intraday unit commitment (UC) adjustment process based on updated ultra-short term wind forecast information is one way to improve the dispatching results. A novel three-stage UC decision method, in which the day-ahead UC decisions are determined in the first stage, the intraday UC adjustment decisions of subfast start units are determined in the second stage, and the UC decisions of fast-start units and dispatching decisions are determined in the third stage is presented. Accordingly, a three-stage birandom UC model is presented, in which the intraday hours-ahead forecasted wind power is formulated as a birandom variable, and the intraday UC adjustment event is formulated as a birandom event. The equilibrium chance constraint is employed to ensure the reliability requirement. A birandom simulation based hybrid genetic algorithm is designed to solve the proposed model. Some computational results indicate that the proposed model provides UC decisions with lower expected total costs.

The Effects of Partnered Exercise on Physical Intimacy in Couples Coping with Prostate Cancer

PubMed Central

Lyons, Karen S.; Winters-Stone, Kerri M.; Bennett, Jill A.; Beer, Tomasz M.

2015-01-01

Objective The study examined whether couples coping with prostate cancer participating in a partnered exercise program - Exercising Together (ET) - experienced higher levels of physical intimacy (i.e., affectionate & sexual behavior) than couples in a usual care (UC) control group. Method Men and their wives (n=64 couples) were randomly assigned to either the ET or UC group. Couples in the ET group engaged in partnered strength-training twice weekly for six months. Multilevel modeling was used to explore the effects of ET on husband and wife engagement in both affectionate and sexual behaviors over time. Results Controlling for relationship quality, wives in ET showed significant increases in engagement in affectionate behaviors compared to wives in UC. No intervention effects were found for husbands. Conclusion Couple-based approaches to physical intimacy, after a cancer diagnosis, that facilitate collaborative engagement in non-sexual physical activities for the couple have potential to be effective for wives. More research is needed in this area to determine couples most amenable to such exercise strategies, optimal timing in the cancer trajectory, and the benefits of combining partnered exercise with more traditional relationship-focused strategies. PMID:26462060

Telemonitoring of CPAP therapy may save nursing time.

PubMed

Anttalainen, Ulla; Melkko, Sari; Hakko, Sirkka; Laitinen, Tarja; Saaresranta, Tarja

2016-12-01

Telemonitoring might enhance continuous positive airway pressure (CPAP) adherence and save nursing time at the commencement of CPAP therapy. We tested wireless telemonitoring (ResTraxx Online System®, ResMed) during the habituation phase of the CPAP therapy in obstructive sleep apnea syndrome (OSAS). In total, 111 consecutive OSAS patients were enrolled. After CPAP titration, patients were followed with the telemonitoring (TM, N = 50) or the usual care (UC, N = 61). The TM group used fixed pressure CPAP device with and the UC group similar device without wireless telemonitoring. Patients and study nurses were unblinded. The evaluated end-points were hours of CPAP use >4 h/day, mask leak <0.4 L/s, and AHI <5/h. Nursing time including extra phone calls, visits, and telemonitoring time was recorded during the habituation phase. CPAP adherence was controlled in the beginning and at the end of the habituation phase and after 1-year of use. TM and UC groups did not differ in terms of patient characteristics. The average length of the habituation phase was 4 weeks in the TM group and fixed 3 months in the UC group. Median nursing time was 39 min (range 12-132 min) in the TM group and shorter compared to that of 58 min (range 40-180 min) (p < 0.001) per patient in the UC group. Both treatment groups had high CPAP usage hours (>4 h/day) and the change in usage at the end of the habituation phase did not differ between the groups (p = 0.39). Patients in both groups were equally satisfied with the treatment protocol. CPAP adherence (6.4 h in TM vs. 6.1 h in UC group, p = 0.63) and residual AHI (1.3 in TM vs. 3.2 in UC group, p = 0.04) were good in both groups at 1-year follow-up. Wireless telemonitoring of CPAP treatment could be relevant in closing the gap between the increasing demand and available health-care resources. It may save nursing time without compromising short- or long-term effectiveness of CPAP treatment in OSAS.

Regional Neuroplastic Brain Changes in Patients with Chronic Inflammatory and Non-Inflammatory Visceral Pain

PubMed Central

Hong, Jui-Yang; Labus, Jennifer S.; Jiang, Zhiguo; Ashe-Mcnalley, Cody; Dinov, Ivo; Gupta, Arpana; Shi, Yonggang; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R.; Tillisch, Kirsten; Mayer, Emeran A.

2014-01-01

Regional cortical thickness alterations have been reported in many chronic inflammatory and painful conditions, including inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), even though the mechanisms underlying such neuroplastic changes remain poorly understood. In order to better understand the mechanisms contributing to grey matter changes, the current study sought to identify the differences in regional alterations in cortical thickness between healthy controls and two chronic visceral pain syndromes, with and without chronic gut inflammation. 41 healthy controls, 11 IBS subjects with diarrhea, and 16 subjects with ulcerative colitis (UC) underwent high-resolution T1-weighted magnetization-prepared rapid acquisition gradient echo scans. Structural image preprocessing and cortical thickness analysis within the region of interests were performed by using the Laboratory of Neuroimaging Pipeline. Group differences were determined using the general linear model and linear contrast analysis. The two disease groups differed significantly in several cortical regions. UC subjects showed greater cortical thickness in anterior cingulate cortical subregions, and in primary somatosensory cortex compared with both IBS and healthy subjects. Compared with healthy subjects, UC subjects showed lower cortical thickness in orbitofrontal cortex and in mid and posterior insula, while IBS subjects showed lower cortical thickness in the anterior insula. Large effects of correlations between symptom duration and thickness in the orbitofrontal cortex and postcentral gyrus were only observed in UC subjects. The findings suggest that the mechanisms underlying the observed gray matter changes in UC subjects represent a consequence of peripheral inflammation, while in IBS subjects central mechanisms may play a primary role. PMID:24416245

The Effectiveness and Cost-Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial.

PubMed

Eldabe, Sam; Thomson, Simon; Duarte, Rui; Brookes, Morag; deBelder, Mark; Raphael, Jon; Davies, Ed; Taylor, Rod

2016-01-01

Patients with "refractory angina" (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health-related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost-effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42-month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow-up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Hybrid constructs for tridimensional correction of the thoracic spine in adolescent idiopathic scoliosis: a comparative analysis of universal clamps versus hooks.

PubMed

Ilharreborde, Brice; Even, Julien; Lefevre, Yan; Fitoussi, Franck; Presedo, Ana; Penneçot, Georges-François; Mazda, Keyvan

2010-02-01

Retrospective study of prospectively collected data. Compare Universal Clamps (UCs) and hooks for the thoracic correction of adolescent idiopathic scoliosis (AIS). In scoliosis surgery, sagittal correction is as important as frontal correction due to the risk of junctional kyphosis. Compared to all-screw constructs, hybrid constructs with lumbar pedicle screws and thoracic hooks or sublaminar wires have been shown to achieve similar coronal correction while providing superior postoperative thoracic kyphosis. The authors used a novel sublaminar thoracic implant, the UC with improvements over sublaminar wires. Hybrid constructs using thoracic UCs were compared to those with thoracic hooks. This series involved 150 patients treated for AIS with hybrid constructs. A total of 75 consecutive patients operated from 2001 to 2003, who had thoracic hooks with in situ contouring, distraction, and compression (Group 1), were compared to 75 consecutive patients operated from 2004 to 2006, who had thoracic UCs with posteromedial translation (Group 2). All had intraoperative somatosensory/motor-evoked potential monitoring and at least 2-years follow-up. Except for follow-up (longer in Group 1), the 2 groups were similar before surgery. The UCs achieved better thoracic coronal correction (P < 0.001), Cincinnati index (P < 0.001), kyphosis (P = 0.02), and apical rotation (P < 0.001). In normokyphotic or hypokyphotic patients, the UC corrected thoracic kyphosis by 11.2 degrees (55%) versus 0.4 degrees (2%) achieved by hooks (P < 0.0001). These differences were stable at last follow-up. There were no intraoperative complications or changes in somatosensory/motor-evoked potentials. UC reduced operative time by 20% (60 minutes; P < 0.001) and blood loss by 23% (250 mL; P < 0.001). Although both of these hybrid constructs efficaciously corrected the coronal and axial deformities in AIS, the results of the UC technique were superior to those achieved with hooks in all 3 planes, especially the sagittal plane. Moreover, the UC technique is straightforward and safe, reducing both operative duration and blood loss.

Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial.

PubMed

Palmer, Jaclyn Bradley; Lane, Deforia; Mayo, Diane; Schluchter, Mark; Leeming, Rosemary

2015-10-01

To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist-selected recorded music intraoperatively (n=69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n=70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n=68). The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P<.001) in anxiety scores preoperatively (mean changes [and standard deviation: -30.9 [36.3], -26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P=.018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable. © 2015 by American Society of Clinical Oncology.

Internet-orientated Assessment of QOL and Actual Treatment Status in Japanese Patients with Inflammatory Bowel Disease: The 3I survey.

PubMed

Matsumoto, Takayuki; Yanai, Shunichi; Toya, Yosuke; Ueno, Masato; Nakamura, Shotaro

2015-06-01

This survey aimed to compare actual lifestyle factors and QOL between Japanese IBD patients and healthy Japanese controls, by questionnaire using an internet-web system. Through the internet-web system, we asked 464 patients with Crohn's disease [CD], 360 patients with ulcerative colitis [UC], and 4100 healthy controls to answer a questionnaire including an eight-item short-form health survey [SF-8]. The survey was conducted until data had been accumulated from the predetermined numbers of patients [120 patients each with CD and UC] and healthy controls [240 subjects]. QOL assessment by SF-8 revealed scores for six of the eight subscale items and the summary score for the mental component to be significantly lower in the CD and UC groups than in controls. There was a significant negative correlation between each SF-8 score and the degree of CD and UC symptoms. The marriage rate in adult patients was significantly lower in the CD than in the UC group or the controls. The mean annual income and the employment rate were significantly lower in the CD than in the UC group or the controls. CD patients receiving biologicals were more frequently satisfied with the efficacy of treatment than UC patients were with their treatment regimens [56% vs 29%]. Actual lifestyle factors and QOL appear to be impaired in Japanese patients with IBD, especially those with CD. The subjective efficacy of biologicals might be greater in CD than in UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers

PubMed Central

2013-01-01

Background UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. Methods This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. Results After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. Conclusions Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities. PMID:24153020

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.

PubMed

Lugo, James P; Saiyed, Zainulabedin M; Lau, Francis C; Molina, Jhanna Pamela L; Pakdaman, Michael N; Shamie, Arya Nick; Udani, Jay K

2013-10-24

UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities.

Screening of the optimized prescription from Suqingwan in terms of its therapeutic effect on DSS-induced ulcerative colitis by its regulation of inflammatory and oxidative mediators.

PubMed

Shao, Jingxuan; Liu, Zhihui; Wang, Lin; Song, Zehai; Chang, Hang; Han, Na; Yin, Jun

2017-04-18

Suqingwan (SQW), a traditional Chinese medicine used for treating ulcerative colitis (UC), is composed of 13 kinds of Traditional Chinese medicines (TCMs). According to TCM theory, we investigated whether a simplified prescription composed of the herbs with some functions, would have similar effects to SQW and examined its potential treatment mechanism of action. We categorized the herbs in SQW into four groups according to their traditional functions and used an orthogonal experimental design to obtain nine separated prescriptions (SPs) of SQW. A dextran sulfate sodium (DSS)-induced UC mouse model was used to evaluate the anti-ulcer colitis effects of the nine SPs and the calculated prescription (CP) was obtained based on the orthogonal t values of the disease activity index (DAI) of the nine SPs. The effect of the CP and SP8 were verified in the DSS-induced UC model, and the DAI and histopathology of the UC mice were examined. Myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4 and IL-10 of the mice in SP8 were investigated to explore the mechanism of action of the optimized prescription with regard to anti-inflammatory and anti-oxidation effects. Among the 9 SPs, separate prescription 6, 7 and 8 (SP6, SP7 and SP8) and the SQW formulation all significantly reduced the DAI of the UC mice and, in particular, SP8 had an effect similar to SQW, which consists of Sanguisorba officinalis L., Rehmannia glutinosa Libosch. and four other herbal medicines. In a further investigation, SP8 was found to improve the ulcerative colitis in mice in terms of both clinical symptoms and histopathology. The mortality of mice in the SP8 group was 33.3%, better than CP based on the orthogonal t values (83.3%). SP8 could also reduce the levels of TNF-α, IL-1β, IL-6, MPO and MDA and increase the levels of IL-4 and IL-10 in colon tissue of UC mice in comparison with those of the model group (p<0.05). An optimized prescription (SP8) from SQW was obtained based on an orthogonal experimental design, which involved 6 herbal medicines, with significantly fewer herbs than in the original prescription. SP8 displayed a similar anti-ulcerative colitis activity to SQW, and its in vivo mechanism of action is related to up-regulation of anti-inflammatory cytokines and down-regulation of pro-inflammatory and oxidative factors. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Are HLA-DR or TAP genes genetic markers of severity in ulcerative colitis?

PubMed

Heresbach, D; Alizadeh, M; Reumaux, D; Colombel, J F; Delamaire, M; Danze, P M; Gosselin, M; Genetet, B; Bretagne, J F; Semana, G

1996-12-01

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n = 91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n = 200) were included. HLA-DRB1*03 was less frequent in UC patients than in healthy controls (8% vs 28%, PC < 0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively, (PC < 0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.

IL-23R mutation is associated with ulcerative colitis: A systemic review and meta-analysis.

PubMed

Peng, Ling-Long; Wang, Ying; Zhu, Feng-Ling; Xu, Wang-Dong; Ji, Xue-Lei; Ni, Jing

2017-01-17

Since a genome-wide association study revealed that Interleukin-23 receptor (IL-23R) gene is a candidate gene for Ulcerative Colitis (UC), many studies have investigated the association between the IL-23R polymorphisms and UC. However, the results were controversial. The aim of the study was to determine whether the IL-23R polymorphisms confer susceptibility to UC. A systematic literature search was carried out to identify all potentially relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. A total of 33 studies in 32 articles, including 10,527 UC cases and 15,142 healthy controls, were finally involved in the meta-analysis. Overall, a significant association was found between all UC cases and the rs11209026A allele (OR = 0.665, 95% CI = 0.604~0.733, P < 0.001). Similarly, meta-analyses of the rs7517847, rs1004819, rs10889677, rs2201841, rs11209032, rs1495965, rs1343151 and rs11465804 polymorphisms also indicated significant association with all UC (all P < 0.05). Stratification by ethnicity revealed that the rs11209026, rs7517847, rs10889677, rs2201841 andrs11465804 polymorphisms were associated with UC in the Caucasian group, but not in Asians, while the rs1004819 and rs11209032 polymorphisms were found to be related to UC for both Caucasian and Asian groups. However, subgroup analysis failed to unveil any association between the rs1495965 and rs1343151 polymorphisms and UC in Caucasians or Asians. The meta-analysis suggests significant association between IL-23R polymorphisms and UC, especially in Caucasians.

IL-23R mutation is associated with ulcerative colitis: A systemic review and meta-analysis

PubMed Central

Peng, Ling-Long; Wang, Ying; Zhu, Feng-Ling; Xu, Wang-Dong; Ji, Xue-Lei; Ni, Jing

2017-01-01

Objectives Since a genome-wide association study revealed that Interleukin-23 receptor (IL-23R) gene is a candidate gene for Ulcerative Colitis (UC), many studies have investigated the association between the IL-23R polymorphisms and UC. However, the results were controversial. The aim of the study was to determine whether the IL-23R polymorphisms confer susceptibility to UC. Methods A systematic literature search was carried out to identify all potentially relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. Results A total of 33 studies in 32 articles, including 10,527 UC cases and 15,142 healthy controls, were finally involved in the meta-analysis. Overall, a significant association was found between all UC cases and the rs11209026A allele (OR = 0.665, 95% CI = 0.604~0.733, P < 0.001). Similarly, meta-analyses of the rs7517847, rs1004819, rs10889677, rs2201841, rs11209032, rs1495965, rs1343151 and rs11465804 polymorphisms also indicated significant association with all UC (all P < 0.05). Stratification by ethnicity revealed that the rs11209026, rs7517847, rs10889677, rs2201841 andrs11465804 polymorphisms were associated with UC in the Caucasian group, but not in Asians, while the rs1004819 and rs11209032 polymorphisms were found to be related to UC for both Caucasian and Asian groups. However, subgroup analysis failed to unveil any association between the rs1495965 and rs1343151 polymorphisms and UC in Caucasians or Asians. Conclusions The meta-analysis suggests significant association between IL-23R polymorphisms and UC, especially in Caucasians. PMID:27902482

Balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes is vital for patients with ulcerative colitis.

PubMed

Dai, Shi-Xue; Wu, Gang; Zou, Ying; Feng, Yan-Ling; Liu, Hong-Bo; Feng, Jin-Shan; Chi, Hong-Gang; Lv, Ru-Xi; Zheng, Xue-Bao

2013-01-01

Immune balances are important for many diseases including ulcerative colitis (UC). This study aimed to explore the role of the balance between CD8+ CD28+ and CD8+ CD28- T lymphocytes for the immunological pathogenesis of UC. Sixteen patients with UC, 16 patients with irritable bowel syndrome (IBS) and 15 healthy volunteers were enrolled. The frequencies of CD8+ CD28+ and CD8+CD28- T lymphocytes in peripheral blood and colon tissue were tested using flow cytometry and immunofluorescent, respectively. The cytokines of the two lymphocytes were detected by protein chips and ELISA. The expression of the signal transducers, the JAK3 and STAT6, as well the transcription factors, the NFATc2 and GATA3, was all detected by both western blot and immunohistochemistry. For UC patients, the frequencies of CD8+ CD28+ T lymphocytes, together with the ratios of CD8+ CD28+ / CD8+ CD28- T lymphocytes in blood and colon tissue, were significantly lower than those in both IBS patients and healthy volunteers. But the frequencies of CD8+ CD28- T lymphocytes in blood and colon tissue of the UC patients were significantly higher than the other two groups. The concentration of IL-7 and -13, and the expression of JAK3 and STAT6 in UC patients, were significantly lower when compared with the other two groups. Conversely, the concentration of IL-12p40 and -15, and the expression of GATA3 and NFATc2 in UC patients, were significantly higher than both IBS and control group. The balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes plays a vital role in UC, while the balance tilt towards CD8+ CD28+ T lymphocytes is beneficial for patients with UC.

Semi-Individualized Homeopathy Add-On Versus Usual Care Only for Premenstrual Disorders: A Randomized, Controlled Feasibility Study.

PubMed

Klein-Laansma, Christien T; Jong, Mats; von Hagens, Cornelia; Jansen, Jean Pierre C H; van Wietmarschen, Herman; Jong, Miek C

2018-03-22

Premenstrual syndrome and premenstrual dysphoric disorder (PMS/PMDD) bother a substantial number of women. Homeopathy seems a promising treatment, but it needs investigation using reliable study designs. The feasibility of organizing an international randomized pragmatic trial on a homeopathic add-on treatment (usual care [UC] + HT) compared with UC alone was evaluated. A multicenter, randomized, controlled pragmatic trial with parallel groups. The study was organized in general and private homeopathic practices in the Netherlands and Sweden and in an outpatient university clinic in Germany. Women diagnosed as having PMS/PMDD, based on prospective daily rating by the daily record of severity of problems (DRSP) during a period of 2 months, were included and randomized. Women were to receive UC + HT or UC for 4 months. Homeopathic medicine selection was according to a previously tested prognostic questionnaire and electronic algorithm. Usual care was as provided by the women's general practitioner according to their preferences. Before and after treatment, the women completed diaries (DRSP), the measure yourself concerns and well-being, and other questionnaires. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. In Germany, the study could not proceed because of legal limitations. In Sweden, recruitment proved extremely difficult. In the Netherlands and Sweden, 60 women were randomized (UC + HT: 28; UC: 32), data of 47/46 women were analyzed (ITT/PP). After 4 months, relative mean change of DRSP scores in the UC + HT group was significantly better than in the UC group (p = 0.03). With respect to recruitment and different legal status, it does not seem feasible to perform a larger, international, pragmatic randomized trial on (semi-)individualized homeopathy for PMS/PMDD. Since the added value of HT compared with UC was demonstrated by significant differences in symptom score changes, further studies are warranted.

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CAMPARE and Cal-Bridge: Two Institutional Networks Increasing Diversity in Astronomy

NASA Astrophysics Data System (ADS)

Rudolph, Alexander L.; Smecker-Hane, Tammy A.

2017-01-01

We describe two programs, CAMPARE and Cal-Bridge, with the common mission of increasing participation of groups traditionally underrepresented in astronomy, through summer research opportunities, in the case of CAMPARE, scholarships in the case of Cal-Bridge, and significant mentoring in both programs, creating a national impact on their numbers successfully pursuing a PhD in the field.In 7 years, the CAMPARE program has sent 80 students, >80% from underrepresented groups, to conduct summer research at one of 14 major research institutions throughout the country. The graduation rate among CAMPARE scholars is 98%, and of the CAMPARE scholars who have graduated with a Bachelor’s degree, more than 60% have completed or are pursuing graduate education in astronomy or a related field, at institutions including UCLA, UC Riverside, UC Irvine, UC Santa Barbara, USC, Stanford, Univ. of Arizona, Univ. of Washington, and the Fisk-Vanderbilt Master’s-to-PhD program.Now entering its third year, the Cal-Bridge program is a CSU-UC Bridge program comprised of over 75 physics and astronomy faculty from 5 University of California (UC), 9 California State University (CSU), and 14 California Community College (CCC) campuses in Southern California. In the first three years, 22 Cal-Bridge Scholars have been selected, including 11 Hispanic, 3 African-American and 8 female students, 5 of whom are from URM groups. Nineteen (19) of the 22 Cal-Bridge Scholars are first-generation college students. The entire first cohort of 4 Cal-Bridge scholars was accepted to one or more PhD programs in astronomy or physics, including UC Irvine, UC Santa Cruz, UC Davis, Michigan State, and Georgia State Universities. The second cohort of 8 Cal-Bridge scholars is applying to graduate schools this fall.Cal-Bridge provides much deeper mentoring and professional development experiences over the last two years of undergraduate and first year of graduate school to students from this diverse network of higher education institutions. Cal-Bridge Scholars benefit from substantial financial support, intensive, joint mentoring by CSU and UC faculty, professional development workshops, and exposure to research opportunities at the participating UC campuses.

The effects of mindfulness-based stress reduction on objective and subjective sleep parameters in women with breast cancer: a randomized controlled trial.

PubMed

Lengacher, Cecile A; Reich, Richard R; Paterson, Carly L; Jim, Heather S; Ramesar, Sophia; Alinat, Carissa B; Budhrani, Pinky H; Farias, Jerrica R; Shelton, Melissa M; Moscoso, Manolete S; Park, Jong Y; Kip, Kevin E

2015-04-01

The purpose of this study was to investigate the effects of mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)) on multiple measures of objective and subjective sleep parameters among breast cancer survivors (BCS). Data were collected using a two-armed randomized controlled design among BCS enrolled in either a 6-week MBSR(BC) program or a usual care (UC) group with a 12-week follow-up. The present analysis is a subset of the larger parent trial (ClinicalTrials.gov Identifier: NCT01177124). Seventy-nine BCS participants (mean age 57 years), stages 0-III, were randomly assigned to either the formal (in-class) 6-week MBSR(BC) program or UC. Subjective sleep parameters (SSP) (i.e., sleep diaries and the Pittsburgh Sleep Quality Index (PSQI)) and objective sleep parameters (OSP) (i.e., actigraphy) were measured at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) or UC program. Results showed indications of a positive effect of MBSR(BC) on OSP at 12 weeks on sleep efficiency (78.2% MBSR(BC) group versus 74.6% UC group, p = 0.04), percent of sleep time (81.0% MBSR(BC) group versus 77.4% UC group, p = 0.02), and less number waking bouts (93.5 in MBSR(BC) group versus 118.6 in the UC group, p < 0.01). Small nonsignificant improvements were found in SSP in the MBSR(BC) group from baseline to 6 weeks (PSQI total score, p = 0.09). No significant relationship was observed between minutes of MBSR(BC) practice and SSP or OSP. These data suggest that MBSR(BC) may be an efficacious treatment to improve objective and subjective sleep parameters in BCS. Copyright © 2014 John Wiley & Sons, Ltd.

A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

PubMed Central

Chen, Lijian; Liu, Meiling; Zhang, Nan; Zhang, Li; Luo, Yuanwei; Liu, Zhenzhong; Dai, Lijun; Jiang, Yiguo

2016-01-01

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury. PMID:26683706

Long-term outcome of patients with distal ulcerative colitis and inflammation of the appendiceal orifice.

PubMed

Naves, Juan E; Lorenzo-Zúñiga, Vicente; Marín, Laura; Mañosa, Míriam; Oller, Blanca; Moreno, Vicente; Zabana, Yamile; Boix, Jaume; Cabré, Eduard; Domènech, Eugeni

2011-12-01

Skip inflammation of the appendiceal orifice has been described in distal UC (UC-IAO) but long-term clinical outcomes are poorly established. Our aim was to evaluate the long-term clinical outcomes of UC-IAO as compared to classic distal UC. Patients with UC-IAO were identified from the local IBD database. Disease outcome and therapeutic requirements during follow-up were accurately collected, and compared with a control group of patients with distal UC without peri-appendiceal involvement matched by disease extent (proctitis/distal), smoking habit, and date and age at diagnosis. Fourteen UC patients were found to have UC-IAO, most of them with initial extent of UC limited to the rectum. All patients were initially managed with mesalazine administered orally (28.5%), topically (28.5%), or in combination (43%). After a median follow-up of 78 months (interquartile range--IQR 45-123) most UC-IAO patients were successfully managed with oral and/or topical aminosalicylates. Only one of them developed proximal disease progression. As compared to controls, no differences in clinical outcomes or therapeutic requirements were found. Patients with UC-IAO tend to present a mild course, with a low probability to develop proximal progression of disease extent or to require immunosuppressive therapy or colectomy.

A Cluster-Randomized, Community-Based, Tribally Delivered Oral Health Promotion Trial in Navajo Head Start Children.

PubMed

Braun, P A; Quissell, D O; Henderson, W G; Bryant, L L; Gregorich, S E; George, C; Toledo, N; Cudeii, D; Smith, V; Johs, N; Cheng, J; Rasmussen, M; Cheng, N F; Santo, W; Batliner, T; Wilson, A; Brega, A; Roan, R; Lind, K; Tiwari, T; Shain, S; Schaffer, G; Harper, M; Manson, S M; Albino, J

2016-10-01

The authors tested the effectiveness of a community-based, tribally delivered oral health promotion (OHP) intervention (INT) at reducing caries increment in Navajo children attending Head Start. In a 3-y cluster-randomized trial, we developed an OHP INT with Navajo input that was delivered by trained Navajo lay health workers to children attending 52 Navajo Head Start classrooms (26 INT, 26 usual care [UC]). The INT was designed as a highly personalized set of oral health-focused interactions (5 for children and 4 for parents), along with 4 fluoride varnish applications delivered in Head Start during academic years of 2011 to 2012 and 2012 to 2013. The authors evaluated INT impact on decayed, missing, and filled tooth surfaces (dmfs) increment compared with UC. Other outcomes included caries prevalence and caregiver oral health-related knowledge and behaviors. Modified intention-to-treat and per-protocol analyses were conducted. The authors enrolled 1,016 caregiver-child dyads. Baseline mean dmfs/caries prevalence equaled 19.9/86.5% for the INT group and 22.8/90.1% for the UC group, respectively. INT adherence was 53% (i.e., ≥3 child OHP events, ≥1 caregiver OHP events, and ≥3 fluoride varnish). After 3 y, dmfs increased in both groups (+12.9 INT vs. +10.8 UC; P = 0.216), as did caries prevalence (86.5% to 96.6% INT vs. 90.1% to 98.2% UC; P = 0.808) in a modified intention-to-treat analysis of 897 caregiver-child dyads receiving 1 y of INT. Caregiver oral health knowledge scores improved in both groups (75.1% to 81.2% INT vs. 73.6% to 79.5% UC; P = 0.369). Caregiver oral health behavior scores improved more rapidly in the INT group versus the UC group (P = 0.006). The dmfs increment was smaller among adherent INT children (+8.9) than among UC children (+10.8; P = 0.028) in a per-protocol analysis. In conclusion, the severity of dental disease in Navajo Head Start children is extreme and difficult to improve. The authors argue that successful approaches to prevention may require even more highly personalized approaches shaped by cultural perspectives and attentive to the social determinants of oral health (ClinicalTrials.gov NCT01116739). © International & American Associations for Dental Research 2016.

French national consensus clinical guidelines for the management of ulcerative colitis.

PubMed

Peyrin-Biroulet, Laurent; Bouhnik, Yoram; Roblin, Xavier; Bonnaud, Guillaume; Hagège, Hervé; Hébuterne, Xavier

2016-07-01

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of multifactorial etiology that primarily affects the colonic mucosa. The disease progresses over time, and clinical management guidelines should reflect its dynamic nature. There is limited evidence supporting UC management in specific clinical situations, thus precluding an evidence-based approach. To use a formal consensus method - the nominal group technique (NGT) - to develop a clinical practice expert opinion to outline simple algorithms and practices, optimize UC management, and assist clinicians in making treatment decisions. The consensus was developed by an expert panel of 37 gastroenterologists from various professional organizations with experience in UC management using the qualitative and iterative NGT, incorporating deliberations based on the European Crohn's and Colitis Organisation recommendations, recent reviews of scientific literature, and pertinent discussion topics developed by a steering committee. Examples of clinical cases for which there are limited evidence-based data from clinical trials were used. Two working groups proposed and voted on treatment algorithms that were then discussed and voted for by the nominal group as a whole, in order to reach a consensus. A clinical practice guideline covering management of the following clinical situations was developed: (i) moderate and severe UC; (ii) acute severe UC; (iii) pouchitis; (iv) refractory proctitis, in the form of treatment algorithms. Given the limited available evidence-based data, a formal consensus methodology was used to develop simple treatment guidelines for UC management in different clinical situations that is now accessible via an online application. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Transition Metal-Involved Photon Upconversion.

PubMed

Ye, Shi; Song, En-Hai; Zhang, Qin-Yuan

2016-12-01

Upconversion (UC) luminescence of lanthanide ions (Ln 3+ ) has been extensively investigated for several decades and is a constant research hotspot owing to its fundamental significance and widespread applications. In contrast to the multiple and fixed UC emissions of Ln 3+ , transition metal (TM) ions, e.g., Mn 2+ , usually possess a single broadband emission due to its 3 d 5 electronic configuration. Wavelength-tuneable single UC emission can be achieved in some TM ion-activated systems ascribed to the susceptibility of d electrons to the chemical environment, which is appealing in molecular sensing and lighting. Moreover, the UC emissions of Ln 3+ can be modulated by TM ions (specifically d -block element ions with unfilled d orbitals), which benefits from the specific metastable energy levels of Ln 3+ owing to the well-shielded 4 f electrons and tuneable energy levels of the TM ions. The electric versatility of d 0 ion-containing hosts ( d 0 normally viewed as charged anion groups, such as MoO 6 6- and TiO 4 4- ) may also have a strong influence on the electric dipole transition of Ln 3+ , resulting in multifunctional properties of modulated UC emission and electrical behaviour, such as ferroelectricity and oxide-ion conductivity. This review focuses on recent advances in the room temperature (RT) UC of TM ions, the UC of Ln 3+ tuned by TM or d 0 ions, and the UC of d 0 ion-centred groups, as well as their potential applications in bioimaging, solar cells and multifunctional devices.

Transition Metal‐Involved Photon Upconversion

PubMed Central

Song, En‐Hai

2016-01-01

Upconversion (UC) luminescence of lanthanide ions (Ln3+) has been extensively investigated for several decades and is a constant research hotspot owing to its fundamental significance and widespread applications. In contrast to the multiple and fixed UC emissions of Ln3+, transition metal (TM) ions, e.g., Mn2+, usually possess a single broadband emission due to its 3d 5 electronic configuration. Wavelength‐tuneable single UC emission can be achieved in some TM ion‐activated systems ascribed to the susceptibility of d electrons to the chemical environment, which is appealing in molecular sensing and lighting. Moreover, the UC emissions of Ln3+ can be modulated by TM ions (specifically d‐block element ions with unfilled d orbitals), which benefits from the specific metastable energy levels of Ln3+ owing to the well‐shielded 4f electrons and tuneable energy levels of the TM ions. The electric versatility of d 0 ion‐containing hosts (d 0 normally viewed as charged anion groups, such as MoO6 6‐ and TiO4 4‐) may also have a strong influence on the electric dipole transition of Ln3+, resulting in multifunctional properties of modulated UC emission and electrical behaviour, such as ferroelectricity and oxide‐ion conductivity. This review focuses on recent advances in the room temperature (RT) UC of TM ions, the UC of Ln3+ tuned by TM or d 0 ions, and the UC of d 0 ion‐centred groups, as well as their potential applications in bioimaging, solar cells and multifunctional devices. PMID:27981015

Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial

PubMed Central

Bradley Palmer, Jaclyn; Lane, Deforia; Mayo, Diane; Schluchter, Mark; Leeming, Rosemary

2015-01-01

Purpose To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. Patients and Methods Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist-selected recorded music intraoperatively (n = 69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n = 70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n = 68). Results The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P < .001) in anxiety scores preoperatively (mean changes [and standard deviation: −30.9 [36.3], −26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P = .018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. Conclusion Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable. PMID:26282640

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.

PubMed

Reissig, Kathrin; Silver, Andrew; Hartig, Roland; Schinlauer, Antje; Walluscheck, Diana; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert; Poehlmann-Nitsche, Angela

2017-01-01

Dysregulation of c-Jun N -terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.

Evaluation of the Role of Umbilical Cord Serum and Autologous Serum Therapy in Reepithelialization After Keratoplasty: A Randomized Controlled Clinical Trial.

PubMed

Kamble, Neha; Sharma, Namrata; Maharana, Prafulla K; Bandivadekar, Pooja; Nagpal, Ritu; Agarwal, Tushar; Velpandian, Thirumurthy; Mittal, Suneeta; Vajpayee, Rasik B

2017-09-01

To evaluate the role of umbilical cord serum (UCS) and autologous serum (AS) therapy in reepithelialization of corneal graft after keratoplasty in a randomized controlled trial. A total of 105 eyes with epithelial defect (ED) after keratoplasty (penetrating keratoplasty-67 and anterior lamellar keratoplasty-38) on the first postoperative day were included in the study. The eyes were randomized into three groups: UCS (n=35), AS (n=35), and artificial tears (AT) (n=35). All patients received standard postoperative medical therapy. The primary outcome measure was time to epithelialization, and secondary outcome measures were best-corrected visual acuity and graft clarity. The ED healed completely in 103 eyes. The mean time for complete reepithelialization was 2.5±2.1, 3.1±2.2, and 4.5±1.4 days in UCS, AS, and AT groups, respectively. The mean percentage decrease in the size of the ED was significantly better in the UCS and AS groups as compared with the AT group (P=0.001). The rate of reepithelialization was comparable between the AS and UCS groups (P=0.3). On bivariate analysis, significant correlation was found between the mean size of postoperative ED, grade of the donor cornea (P=0.001), and the presence of preoperative ED (P=0.001). No complications were associated with the use of serum therapy. Most of the cases of postkeratoplasty corneal ED can be managed with AT only. The serum therapy (AS/UCS) helps in the faster reepithelialization of postkeratoplasty ED as compared with AT and may be considered as a treatment option for early epithelial healing.

A Novel Model for Predicting Incident Moderate to Severe Anemia and Iron Deficiency in Patients with Newly Diagnosed Ulcerative Colitis.

PubMed

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Yang, Yu-Xiao

2017-05-01

Anemia and iron deficiency are common complications of ulcerative colitis (UC). We aimed to develop and internally validate a prediction model for the incidence of moderate to severe anemia and iron deficiency anemia (IDA) in newly diagnosed patients with UC. Multivariable logistic regression was performed among a nationwide cohort of patients who were newly diagnosed with UC in the VA health-care system. Model development was performed in a random two-third of the total cohort and then validated in the remaining one-third of the cohort. As candidate predictors, we examined routinely available data at the time of UC diagnosis including demographics, medications, laboratory results, and endoscopy findings. A total of 789 patients met the inclusion criteria. For the outcome of moderate to severe anemia, age, albumin level and mild anemia at UC diagnosis were predictors selected for the model. The AUC for this model was 0.69 (95% CI 0.64-0.74). For the outcome of moderate to severe anemia with evidence of iron deficiency, the predictors included African-American ethnicity, mild anemia, age, and albumin level at UC diagnosis. The AUC was 0.76, (95% CI 0.69-0.82). Calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit p > 0.05). The models performed similarly in the internal validation cohort. We developed and internally validated a prognostic model for predicting the risk of moderate to severe anemia and IDA among newly diagnosed patients with UC. This will help identify patients at high risk of these complications, who could benefit from surveillance and preventive measures.

Graduate and Professional School Applications, Admissions and Enrollments (1981-1988): A Status Report on Ethnic Groups Underrepresented at UC Davis. Research Synopsis No. 29.

ERIC Educational Resources Information Center

California Univ., Davis. Office of Student Affairs Research and Information.

This report describes postgraduate enrollment trends for ethnic groups underrepresented at University of California, Davis. The UC Davis Student Affirmative Action (SAA) Plan identifies the following groups as underrepresented in both the Graduate Division and professional schools: American Indian, Black/African-American, Chicano/Mexican American,…

Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice

PubMed Central

Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

2016-01-01

Aim To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Methods Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. Results The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Conclusions Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L. fermentum CCTCC M206110 proved to be effective at attenuating DSS-induced colitis. The potential probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed. PMID:26840426

Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice.

PubMed

Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

2016-01-01

To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L. fermentum CCTCC M206110 proved to be effective at attenuating DSS-induced colitis. The potential probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed.

Predictors of Outcome in Ulcerative Colitis.

PubMed

Waterman, Matti; Knight, Jo; Dinani, Amreen; Xu, Wei; Stempak, Joanne M; Croitoru, Kenneth; Nguyen, Geoffrey C; Cohen, Zane; McLeod, Robin S; Greenberg, Gordon R; Steinhart, A Hillary; Silverberg, Mark S

2015-09-01

Approximately 80% of patients with ulcerative colitis (UC) have intermittently active disease and up to 20% will require a colectomy, but little data available on predictors of poor disease course. The aim of this study was to identify clinical and genetic markers that can predict prognosis. Medical records of patients with UC with ≥5 years of follow-up and available DNA and serum were retrospectively assessed. Immunochip was used to genotype loci associated with immune mediated inflammatory disorders (IMIDs), inflammatory bowel diseases, and other single nucleotide polypmorphisms previously associated with disease severity. Serum levels of pANCA, ASCA, CBir1, and OmpC were also evaluated. Requirement for colectomy, medication, and hospitalization were used to group patients into 3 prognostic groups. Six hundred one patients with UC were classified as mild (n = 78), moderate (n = 273), or severe disease (n = 250). Proximal disease location frequencies at diagnosis were 13%, 21%, and 30% for mild, moderate, and severe UC, respectively (P = 0.001). Disease severity was associated with greater proximal extension rates on follow-up (P < 0.0001) and with shorter time to extension (P = 0.03) and to prednisone initiation (P = 0.0004). When comparing severe UC with mild and moderate UC together, diagnosis age >40 and proximal disease location were associated with severe UC (odds ratios = 1.94 and 2.12, respectively). None of the single nucleotide polypmorphisms or serum markers tested was associated with severe UC, proximal disease extension or colectomy. Older age and proximal disease location at diagnosis, but not genetic and serum markers, were associated with a more severe course. Further work is required to identify biomarkers that will predict outcomes in UC.

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds.

PubMed

Baumgart, Daniel C; le Claire, Marie

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. DRGs challenge sophisticated IBD care.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

PubMed

Hou, Chen; Peng, Danyi; Gao, Li; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Chen, Hong; Zou, Lin; Fu, Zhou

2018-01-08

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O 2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation. Copyright © 2017. Published by Elsevier Inc.

A Model of Integrative Care for Low-Back Pain

PubMed Central

Buring, Julie E.; Hrbek, Andrea L.; Davis, Roger B.; Connelly, Maureen T.; Cherkin, Daniel C.; Levy, Donald B.; Cunningham, Mark; O'Connor, Bonnie; Post, Diana E.

2012-01-01

Abstract Objectives While previous studies focused on the effectiveness of individual complementary and alternative medical (CAM) therapies, the value of providing patients access to an integrated program involving multiple CAM and conventional therapies remains unknown. The objective of this study is to explore the feasibility and effects of a model of multidisciplinary integrative care for subacute low-back pain (LBP) in an academic teaching hospital. Design This was a pilot randomized trial comparing an individualized program of integrative care (IC) plus usual care to usual care (UC) alone for adults with LBP. Subjects Twenty (20) individuals with LPB of 3–12 weeks' duration were recruited from an occupational health clinic and community health center. Interventions Participants were randomized to 12 weeks of individualized IC plus usual care versus UC alone. IC was provided by a trained multidisciplinary team offering CAM therapies and conventional medical care. Outcome measures The outcome measures were symptoms (pain, bothersomeness), functional status (Roland-Morris score), SF-12, worry, and difficulty performing three self-selected activities. Results Over 12 weeks, participants in the IC group had a median of 12.0 visits (range 5–25). IC participants experienced significantly greater improvements at 12 weeks than those receiving UC alone in symptom bothersomeness (p=0.02) and pain (p=0.005), and showed greater improvement in functional status (p=0.08). Rates of improvement were greater for patients in IC than UC in functional status (p=0.02), bothersomeness (p=0.002), and pain scores (p=0.001). Secondary outcomes of self-selected most challenging activity, worry, and the SF-12 also showed improvement in the IC group at 12 weeks. These differences persisted at 26 weeks, but were no longer statistically significant. Conclusions It was feasible for a multidisciplinary, outpatient IC team to deliver coordinated, individualized intervention to patients with subacute LBP. Results showed a promising trend for benefit of treating patients with persistent LBP with this IC model, and warrant evaluation in a full-scale study. PMID:22455544

Effects of Changtai granules, a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats

PubMed Central

Cao, Yong-Bing; Zhang, Jun-Dong; Diao, Ya-Ying; Yan, Lan; Wang, De-Jun; Jia, Xin-Ming; Gao, Ping-Hui; Cheng, Ming-He; Xu, Zheng; Wang, Yan; Jiang, Yuan-Ying

2005-01-01

AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250-300 g, were employed in the present study. The rat colitis models were induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg in 50% ethanol. The experimental animals were randomly divided into dexamethasone (DX) treatment, CTG treatment, and model control groups, which were intracolicly treated daily with DX (0.2 mg/kg), CTG at doses of 2.9, 5.7 and 11.4 g crude drug/kg, and the equal amount of saline respectively from 6 h following induction of the colitis in rats inflicted with TNBS to the end of study. A normal control group of rats treated without TNBS but saline enema was also included in the study. After 3 wk of treatment, the animals were assessed for colonal inflammatory and ulcerative responses with respect to mortality, frequency of diarrhea, histology and myeloperoxidase activity (MPO). RESULTS: The therapeutic effect of CTG on ulcerative colitis (UC) was better than DX. CTG effectively inhibited the activity of granulocytes, macrophages and monocytes in a dose-dependent manner. Also it reduced MPO and formation of inflammation in colonic mucosal tissue. Furthermore, administration of CTG significantly prevented body mass loss and death, and decreased frequency of diarrhea in UC rats, when compared with the model control group rats. CONCLUSION: CTG would prove to be an ideal drug for chronic UC, and is warranted to be studied further. PMID:15962370

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer's disease.

PubMed

Wang, Xinxin; Ma, Shanshan; Yang, Bo; Huang, Tuanjie; Meng, Nan; Xu, Ling; Xing, Qu; Zhang, Yanting; Zhang, Kun; Li, Qinghua; Zhang, Tao; Wu, Junwei; Yang, Greta Luyuan; Guan, Fangxia; Wang, Jian

2018-02-26

Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer's disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD. Copyright © 2017. Published by Elsevier B.V.

Effects of curcumin plus Soy oligosaccharides on intestinal flora of rats with ulcerative colitis.

PubMed

Huang, G; Ye, L; Du, G; Huang, Y; Wu, Y; Ge, S; Yang, Z; Zhu, G

2017-08-15

To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay). Colonic tissues with the most obvious lesions were obtained using a surgical scissor. A routine hematoxylin-eosin (HE) staining method was used to stain pathological specimens and images of staining results were obtained. Histological injury scores of colonic mucosa were calculated. Ulcerative colitis model rats had the highest macroscopic damage scores and histological injury scores of colonic mucosa. After treatment the contents of TNF-α and IL-8 decreased significantly in the group of curcumin plus soy oligosaccharide compared with the model group with statistical significance (P <0.01) while the contents were close to those in the SASP group. There was no statistical significance (P> 0.05). The treatment could decrease TNF-α and IL- 8 expression and reduce colonic mucosa inflammation and tissue damage.

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis.

PubMed

Parian, Alyssa; Limketkai, Berkeley; Koh, Joyce; Brant, Steven R; Bitton, Alain; Cho, Judy H; Duerr, Richard H; McGovern, Dermot P; Proctor, Deborah D; Regueiro, Miguel D; Rioux, John D; Schumm, Phil; Taylor, Kent D; Silverberg, Mark S; Steinhart, A Hillary; Hernaez, Ruben; Lazarev, Mark

2017-08-01

Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Family partnership and education interventions to reduce dietary sodium by patients with heart failure differ by family functioning.

PubMed

Dunbar, Sandra B; Clark, Patricia C; Stamp, Kelly D; Reilly, Carolyn M; Gary, Rebecca A; Higgins, Melinda; Kaslow, Nadine

2016-01-01

Determine if family functioning influences response to family-focused interventions aimed at reducing dietary sodium by heart failure (HF) patients. Lowering dietary sodium by HF patients often occurs within the home and family context. Secondary analysis of 117 dyads randomized to patient and family education (PFE), family partnership intervention (FPI) or usual care (UC). Dietary sodium measures were obtained from 3-day food record and 24-h urine samples. In the poor family functioning groups, FPI and PFE had lower mean urine sodium than UC (p < .05) at 4 months, and FPI remained lower than UC at 8 months (p < .05). For good family functioning groups, FPI and PFE had lower mean sodium levels by 3-day food record at 4 and 8 months compared to the UC group. Optimizing family-focused interventions into HF clinical care maybe indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding

PubMed Central

Silver, Andrew; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert

2017-01-01

Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression. PMID:28751935

Interleukin 27 is up-regulated in patients with active inflammatory bowel disease.

PubMed

Furuzawa Carballeda, Janette; Fonseca Camarillo, Gabriela; Yamamoto-Furusho, Jesús K

2016-08-01

The aim of the study was to characterize and quantify tissue gene and protein expression of IL-27 in ulcerative colitis (UC) and Crohn's disease (CD) patients. This is an observational and cross-sectional study. Fifty-four patients with IBD were studied: 27 active UC, 12 inactive UC, 10 active CD, and 5 inactive CD. All patients belonged to the Inflammatory Bowel Disease Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición. We found that IL-27 gene expression was significantly higher in active UC versus inactive UC group (P = 0.015). The IL-27 mRNA expression was increased in patients with active CD compared with inactive CD disease (P = 0.035). The percentage of IL-27 immunoreactive cells was higher in active UC versus active CD patients and non-inflamed tissue controls. The IL-27 was significantly elevated in active UC and CD patients, and it was associated with disease severity.

Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora.

PubMed

Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Tian, Hongliang; Ding, Chao; Gu, Lili; Li, Ning; Li, Jieshou

2016-11-03

Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients. Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment. Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC. Current Controlled Trial NCT02016469 . Registered 10 November 2013.

Overexpressed Calponin3 by Subsonic Vibration Induces Neural Differentiation of hUC-MSCs by Regulating the Ionotropic Glutamate Receptor.

PubMed

Kim, Hyun-Jung; Kim, Jin-Hee; Song, Yeo-Ju; Seo, Young-Kwon; Park, Jung-Keug; Kim, Chan-Wha

2015-09-01

In this study, we used proteomics to investigate the effects of sonic vibration (SV) on mesenchymal stem cells derived from human umbilical cords (hUC-MSCs) during neural differentiation to understand how SV enhances neural differentiation of hUC-MSCs. We investigated the levels of gene and protein related to neural differentiation after 3 or 5 days in a group treated with 40-Hz SV. In addition, protein expression patterns were compared between the control and the 40-Hz SV-treated hUC-MSC groups via a proteomic approach. Among these proteins, calponin3 (CNN3) was confirmed to have 299 % higher expression in the 40-Hz SV stimulated hUC-MSCs group than that in the control by Western blotting. Notably, overexpression of CNN3-GFP in Chinese hamster ovary (CHO)-K1 cells had positive effects on the stability and reorganization of F-actin compared with that in GFP-transfected cells. Moreover, CNN3 changed the morphology of the cells by making a neurite-like form. After being subjected to SV, messenger RNA (mRNA) levels of glutamate receptors such as PSD95, GluR1, and NR1 as well as intracellular calcium levels were upregulated. These results suggest that the activity of glutamate receptors increased because of CNN3 characteristics. Taken together, these results demonstrate that overexpressed CNN3 during SV increases expression of glutamate receptors and promotes functional neural differentiation of hUC-MSCs.

Vitamin K nutritional status and undercarboxylated osteocalcin in postmenopausal osteoporotic women treated with bisphosphonates.

PubMed

Iwamoto, Jun; Takada, Tetsuya; Sato, Yoshihiro

2014-01-01

Serum undercarboxylated osteocalcin (ucOC) is an index of vitamin K nutritional status in treatment-naive postmenopausal osteoporotic women. The purpose of the present study was to reveal the association between vitamin K nutritional status and serum ucOC concentrations in postmenopausal osteoporotic women taking bisphosphonates. Eighty-six postmenopausal women with osteoporosis (age range: 47-90 years) initiated bisphosphonate treatment. Vitamin K nutritional status was evaluated using a simple vitamin K-intake questionnaire and serum ucOC concentrations were measured after 6 months of treatment. The patients were divided into two groups according to the simple vitamin K-intake questionnaire score: a low vitamin K-intake (score <40) group (n=67) and a normal vitamin K-intake (score >=40) group (n=19). There were no significant differences between the groups in baseline parameters including age, height, body weight, body mass index, serum alkaline phosphatase (ALP), urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and changes in serum ALP and urinary NTX concentrations during the 6-month treatment period. However, the mean serum ucOC concentration after 6 months of treatment was significantly higher in the low vitamin K-intake group (2.79 ng/mL) than in the normal vitamin K-intake group (2.20 ng/mL). These results suggest that 78% of postmenopausal osteoporotic women treated with bisphosphonates may have vitamin K deficiency as indicated by low vitamin K-intake and high serum ucOC concentrations, despite having a similar reduction in bone turnover to women who have normal vitamin K-intake.

Lifestyle educational program strongly increases compliance to nonpharmacologic intervention in hypertensive patients: a 2-year follow-up study.

PubMed

Ferrara, Aldo L; Pacioni, Delia; Di Fronzo, Valentina; Russo, Barbara F; Staiano, Laura; Speranza, Enza; Gente, Rosaria; Gargiulo, Francesco; Ferrara, Fabio

2012-11-01

The authors investigated the efficacy of a lifestyle educational program, organized in small group meetings, in improving the outcome of a nonpharmacologic intervention. One hundred and eighty-eight hypertensive patients with stable blood pressure (BP) levels and drug therapy in the previous 6 months were randomly divided into educational care (EC) and usual care (UC) groups. They were followed at 3-month intervals up to 2 years. In addition to the visits in an outpatient clinic, patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment. At baseline, EC and UC groups were similar for age, sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic treatment. Patients in the EC group had significantly reduced total energy, total and saturated fats, and sodium intake. Physical activity was significantly increased in the EC group as well. At the end of the 1-year follow-up, BMI (P<.001), visceral fat (P<.001), and BP (P<.001) were significantly lower in the EC group compared with the UC group. Pharmacologic treatment during the study was similar for all classes of drugs apart from diuretics whose dose was higher in the UC group at the end of the study. © 2012 Wiley Periodicals, Inc.

Prenatal emotion management improves obstetric outcomes: a randomized control study

PubMed Central

Huang, Jian; Li, He-Jiang; Wang, Jue; Mao, Hong-Jing; Jiang, Wen-Ying; Zhou, Hong; Chen, Shu-Lin

2015-01-01

Introduction: Negative emotions can cause a number of prenatal problems and disturb obstetric outcomes. We determined the effectiveness of prenatal emotional management on obstetric outcomes in nulliparas. Methods: All participants completed the PHQ-9 at the baseline assessment. Then, the participants were randomly assigned to the emotional management (EM) and usual care (UC) groups. The baseline evaluation began at 31 weeks gestation and the participants were followed up to 42 days postpartum. Each subject in the EM group received an extra EM program while the participants in the UC groups received routine prenatal care and education only. The PHQ-9 and Edinburgh Postnatal Depression scale (EPDS) were used for assessment. Results: The EM group had a lower PHQ-9 score at 36 weeks gestation, and 7 and 42 days after delivery (P < 0.01), and a lower EPDS score 42 days postpartum (P < 0.05). The rate of cesarean section in the EM group was lower than the UC group (P < 0.01), and the cesarean section rate without a medical indication was lower (P < 0.01). The duration of the second stage of labor in the EM group was shorter than the UC group (P < 0.01). Conclusions: Prenatal EM intervention could control anxiety and depressive feelings in nulliparas, and improve obstetric outcomes. It may serve as an innovative approach to reduce the cesarean section rate in China. PMID:26309641

Comparison of particle morphology between commercial- and research-grade calcium hydroxide in endodontics.

PubMed

Komabayashi, Takashi; Ahn, Chul; Spears, Robert; Zhu, Qiang

2014-09-01

Ca(OH)2 aqueous slurry is widely used as an inter-appointment antimicrobial dressing in root canal treatment. The aim of this study was to quantify the particle size and shape of commercial-grade UltraCal XS (UC) and to compare it with that of research-grade Ca(OH)2 (RG) using a flow particle image analyzer (FPIA). The morphology and penetration inside the dentin tubules of the UC and RG particles were examined using a scanning electron microscope (SEM). UC and RG (10 mg) were mixed with 15 mL of alcohol, and were sonicated. Five milliliters of the dispersion was subjected to FPIA, and particle length, width, perimeter and aspect ratio were analyzed. In addition, UC paste and RG aqueous slurry were agitated on dentin discs and were prepared for SEM examination. There were significant differences between UC and RG with regard to the frequency of different length groups (P < 0.0001). UC contained smaller particles than RG (P < 0.0001). Under SEM, the agitated UC and RG particles occluded the opening of dentin tubules and penetrated inside the dentin tubules. The size of UC particles is smaller than those of RG. Both UC and RG particles were able to penetrate into open dentin tubules.

Comparison of particle morphology between commercial- and research-grade calcium hydroxide in endodontics

PubMed Central

Komabayashi, Takashi; Ahn, Chul; Spears, Robert; Zhu, Qiang

2014-01-01

Ca(OH)2 aqueous slurry is widely used as an inter-appointment antimicrobial dressing in root canal treatment. The aim of this study was to quantify the particle size and shape of commercial-grade UltraCal XS (UC) and to compare it with that of research-grade Ca(OH)2 (RG) using a flow particle image analyzer (FPIA). The morphology and penetration inside the dentin tubules of the UC and RG particles were examined using a scanning electron microscope (SEM). UC and RG (10 mg) were mixed with 15 mL of alcohol, and were sonicated. Five milliliters of the dispersion was subjected to FPIA, and particle length, width, perimeter and aspect ratio were analyzed. In addition, UC paste and RG aqueous slurry were agitated on dentin discs and were prepared for SEM examination. There were significant differences between UC and RG with regard to the frequency of different length groups (P < 0.0001). UC contained smaller particles than RG (P < 0.0001). Under SEM, the agitated UC and RG particles occluded the opening of dentin tubules and penetrated inside the dentin tubules. The size of UC particles is smaller than those of RG. Both UC and RG particles were able to penetrate into open dentin tubules. PMID:25231145

Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

PubMed

Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2014-08-01

Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Fan, Ruo-Jing; Guan, Qing; Zhang, Fang; Leng, Jia-Peng; Sun, Tuan-Qi; Guo, Yin-Long

2016-02-18

Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Stochastic Optimization for Unit Commitment-A Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Qipeng P.; Wang, Jianhui; Liu, Andrew L.

2015-07-01

Optimization models have been widely used in the power industry to aid the decision-making process of scheduling and dispatching electric power generation resources, a process known as unit commitment (UC). Since UC's birth, there have been two major waves of revolution on UC research and real life practice. The first wave has made mixed integer programming stand out from the early solution and modeling approaches for deterministic UC, such as priority list, dynamic programming, and Lagrangian relaxation. With the high penetration of renewable energy, increasing deregulation of the electricity industry, and growing demands on system reliability, the next wave ismore » focused on transitioning from traditional deterministic approaches to stochastic optimization for unit commitment. Since the literature has grown rapidly in the past several years, this paper is to review the works that have contributed to the modeling and computational aspects of stochastic optimization (SO) based UC. Relevant lines of future research are also discussed to help transform research advances into real-world applications.« less

Inflamed site-specific drug delivery system based on the interaction of human serum albumin nanoparticles with myeloperoxidase in a murine model of experimental colitis.

PubMed

Iwao, Yasunori; Tomiguchi, Izumi; Domura, Ayaka; Mantaira, Yusuke; Minami, Akira; Suzuki, Takashi; Ikawa, Takashi; Kimura, Shin-Ichiro; Itai, Shigeru

2018-04-01

To develop a new strategy for inflamed site-specific drug delivery in the colon for the treatment of ulcerative colitis (UC), we leveraged on the interaction between myeloperoxidase (MPO) and human serum albumin (HSA) and prepared nanoparticles (HSA NPs) conjugated with 5-aminosalicylic acid (5-ASA). The 5-ASA-HSA NPs (nine molecules of 5-ASA per HSA molecule) were uniform particles with an average particle size of 190 nm, a zeta potential of --11.8 mV, and a polydispersity index of 0.35. This was considered a suitable particle characteristic to pass through the mucus layer and accumulate into the mucosa. The specific interaction between the 5-ASA-HSA NPs and MPO was observed using quartz crystal microbalance analysis in vitro. In addition, the 5-ASA-HSA NPs group containing one thousandth of the dose of the 5-ASA (75 μg/kg) showed significantly lower disease activity index values and colon weight/length ratios in UC model mice as similar to large amount of neat 5-ASA group (75 mg/kg), indicating that the therapeutic effect of the 5-ASA-HSA NP formulation was confirmed in vivo. Microscopic images of tissue sections of colon extracted from UC model mice demonstrated that HSA NPs and MPO were both localized in the colon, and this specific interaction between HSA NPs and MPO would be involved the in the therapeutic effect in vivo. Furthermore, in the 5-ASA and 5-ASA-HSA NPs groups, some inflammatory damage was observed in the colon, but the degree of damage was mild compared with the control and HSA NPs groups, suggesting mucosal repair and replacement with fibrous granulation tissue had occurred. Therefore, these data demonstrated that an HSA NP formulation has the potential to specifically deliver 5-ASA to an inflamed site where MPO is highly expressed. Copyright © 2018 Elsevier B.V. All rights reserved.

Usefulness of rectally administering [1-(13)C]-butyrate for breath test in patients with active and quiescent ulcerative colitis.

PubMed

Kato, Kimitoshi; Ishii, Yukimoto; Mizuno, Shigeaki; Sugitani, Masahiko; Asai, Satoshi; Kohno, Tadashi; Takahashi, Katsuyuki; Komuro, Sachiko; Iwamoto, Maho; Miyamoto, Shunpachi; Takayama, Tadatoshi; Arakawa, Yasuyuki

2007-02-01

Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.

Healing acceleration of acetic acid-induced colitis by marigold (Calendula officinalis) in male rats.

PubMed

Tanideh, Nader; Jamshidzadeh, Akram; Sepehrimanesh, Masood; Hosseinzadeh, Masood; Koohi-Hosseinabadi, Omid; Najibi, Asma; Raam, Mozhdeh; Daneshi, Sajad; Asadi-Yousefabad, Seyedeh-Leili

2016-01-01

Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats.

Long-term outcomes of a cell phone-delivered intervention for smokers living with HIV/AIDS.

PubMed

Gritz, Ellen R; Danysh, Heather E; Fletcher, Faith E; Tami-Maury, Irene; Fingeret, Michelle Cororve; King, Rachel Marks; Arduino, Roberto C; Vidrine, Damon J

2013-08-01

People living with human immunodeficiency virus (HIV)/AIDS (PLWHA) have a substantially higher prevalence of cigarette smoking compared to the general population. In addition, PLWHA are particularly susceptible to the adverse health effects of smoking. Our primary objective was to design and test the efficacy over 12 months of a smoking cessation intervention targeting PLWHA. Participants were enrolled from an urban HIV clinic with a multiethnic and economically disadvantaged patient population. Participants received smoking cessation treatment either through usual care (UC) or counseling delivered by a cell phone intervention (CPI). The 7-day point prevalence abstinence was evaluated at 3, 6, and 12 months using logistic regression and generalized linear mixed models. We randomized 474 HIV-positive smokers to either the UC or CPI group. When evaluating the overall treatment effect (7-day abstinence outcomes from 3-, 6-, and 12-month follow-ups), participants in the CPI group were 2.41 times (P = .049) more likely to demonstrate abstinence compared to the UC group. The treatment effect was strongest at the 3-month follow-up (odds ratio = 4.3, P < .001), but diminished at 6 and 12 months (P > .05). Cell phone-delivered smoking cessation treatment has a positive impact on abstinence rates compared to a usual care approach. Future research should focus on strategies for sustaining the treatment effect in the long term.

Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease.

PubMed

de Witte, Samantha F H; Merino, Ana M; Franquesa, Marcella; Strini, Tanja; van Zoggel, Johanna A A; Korevaar, Sander S; Luk, Franka; Gargesha, Madhu; O'Flynn, Lisa; Roy, Debashish; Elliman, Steve J; Newsome, Philip N; Baan, Carla C; Hoogduijn, Martin J

2017-06-08

Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE 2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl 4 -induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model. IFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFβ and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-β, TGFβ and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl 4 -induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB 6 ), ucMSC(Starv + VitB 6 ) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFβ) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC. The present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.

Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.

PubMed

Reinisch, Walter; Panés, Julián; Khurana, Sunil; Toth, Gabor; Hua, Fei; Comer, Gail M; Hinz, Michelle; Page, Karen; O'Toole, Margot; Moorehead, Tara McDonnell; Zhu, Hua; Sun, YanHui; Cataldi, Fabio

2015-06-01

Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. ClinicalTrials.gov number NCT01284062. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparison of treatment outcomes according to output voltage during shockwave lithotripsy for ureteral calculi: a prospective randomized multicenter study.

PubMed

Park, Jinsung; Kim, Hong-Wook; Hong, Sungwoo; Yang, Hee Jo; Chung, Hong

2015-05-01

To investigate the effect of fixed versus escalating voltage during SWL on treatment outcomes in patients with ureteral calculi (UC). A prospective, randomized, multicenter trial was conducted on 120 patients who were diagnosed with a single radiopaque UC. The patients were randomized into group C (n = 60, constant 13 kV, 3,000 shock wave, 2 Hz) or group E (n = 60, 11.4-12.0-13 kV per 1,000 shock waves, 2 Hz). They were evaluated by plain abdominal radiography and urinalysis at 1 week after a single session of SWL, and repeat SWL was performed if needed. The primary endpoint was stone-free rate at 1 week (SFR1) after SWL. Secondary endpoints were post-SWL visual pain score (VPS), oral analgesic requirements during 1 week, and cumulative SFRs after the second and third sessions of SWL. Groups C and E were well balanced in terms of baseline patients and stone characteristics, including pre-SWL VPS, stone location, and stone size (6.24 ± 1.92 vs. 6.30 ± 2.13 mm). SFR1s were not significantly different between groups C and E (60.0 vs. 68.3%, p = 0.447). Analyses stratified by stone size (<6 vs. ≥6 mm) showed no difference in SFR1 (p = 0.148 vs. 0.808). In the analyses stratified by stone location, group E tended to be more effective in distal UC (81.0 vs. 50.0%, p = 0.052), whereas no difference was seen in proximal UC (p = 0.487). Secondary endpoints were also similar between the two groups. Our results suggest that voltage escalation during SWL in UC may not provide superior stone fragmentation compared to fixed voltage.

Urethral versus suprapubic catheter: choosing the best bladder management for male spinal cord injury patients with indwelling catheters.

PubMed

Katsumi, H K; Kalisvaart, J F; Ronningen, L D; Hovey, R M

2010-04-01

Bladder management for male patients with spinal cord injury (SCI) challenges the urologist to work around physical and social restrictions set forth by each patient. The objective of this study was to compare the complications associated with urethral catheter (UC) versus suprapubic tube (SPT) in patients with SCI. A retrospective review of records at Long Beach Veterans Hospital was carried out to identify SCI patients managed with SPT or UC. Chart review identified morbidities including urinary tract infection (UTI), bladder stones, renal calculi, urethral complications, scrotal abscesses, epididymitis, gross hematuria and cancer. Serum creatinine measurements were evaluated to determine whether renal function was maintained. In all, 179 patients were identified. There was no significant difference between the two catheter groups in any areas in which they could be compared. There were catheter-specific complications specific to each group that could not be compared. These included erosion in the UC group and urethral leak, leakage from the SPT and SPT revision in the SPT group. Average serum creatinine for the UC and SPT groups was 0.74 and 0.67 mg per 100 ml, respectively. SCI patients with a chronic catheter have similar complication rates of UTIs, recurrent bladder/renal calculi and cancer. Urethral and scrotal complications may be higher with UC; however, morbidity from SPT-specific procedures may offset benefits from SPT. Serum creatinine was maintained in both groups. Overall, bladder management for patients with chronic indwelling catheters should be selected on the basis of long-term comfort for the patient and a physician mind-set that allows flexibility in managing these challenges.

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds

PubMed Central

Baumgart, Daniel C.; le Claire, Marie

2016-01-01

Background Crohn’s disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. Methods IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Results Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. Conclusions DRGs challenge sophisticated IBD care. PMID:26784027

Maximizing the Efficiency of MAGTF Airlift Capacity in WestPac

DTIC Science & Technology

2013-03-27

respectively, cover the realm of medium-long range, medium lift capabilities. The UC -35 and the UC -12 aircraft, for short-medium range, light lift...requirements, are variations similar to the Cessna Citation and Beechcraft King Air respectively. In addition, the upgraded UC -12W model possesses an...airlift are resident to the VMGR and H&HS squadrons, specifically, the KC-130 and the OSA C- 12 and UC -35 aircraft, respectively. Each of these units

The Berkeley UNIX Consultant Project

DTIC Science & Technology

1987-08-01

of the National Conference on Artifcial Intelligence . Pittsburgh, PA. (2) Chin, D. N. 1986. User modeling in UC, the UNIX consultant. In Proceedings of...Codes Avalt and I1of Dis Special 1. Introduction Several years ago, we began a project called UC (UNIX Consultant). UC was to function as an intelligent ...English. We sometimes refer to UC as "an intelligent ’help’ facility" to emphasize our intention to construct a consul- tation system, rather than a

Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model

PubMed Central

2012-01-01

Background Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. Methods 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. Results At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Conclusions Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels. PMID:22361346

Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model.

PubMed

Homayounfar, Kia; Meis, Johanna; Jung, Klaus; Klosterhalfen, Bernd; Sprenger, Thilo; Conradi, Lena-Christin; Langer, Claus; Becker, Heinz

2012-02-23

Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels.

Associations between NRAMP1 Polymorphisms and Susceptibility to Ulcerative Colitis/Crohn's Disease: A Meta-Analysis.

PubMed

Sun, Manyi; Zhang, Li; Shi, Songli

2016-01-01

Multiple environmental and genetic factors contribute to the risks of ulcerative colitis (UC) and Crohn's disease (CD). Several allelic variants have been identified in natural resistance associated macrophage protein 1 (NRAMP1) gene; however, their association with UC/CD remains conflicting. The purpose of this study was to evaluate whether NRAMP1 polymorphisms are associated with the susceptibility to UC/CD. A meta-analysis on the association between the NRAMP1 polymorphisms and susceptibility to UC/CD was performed. Relevant studies were retrieved from the databases. After eligible data were extracted, Mantel-Haenszel statistics and random/fixed effects model were applied to calculate the pooled odds radio (OR) and 95% confidence interval (95% CI). Seven articles containing 536 UC cases, 997 CD cases, and 1361 controls were collected. No significant association between allele 2 frequency of NRAMP1 and susceptibility to UC/CD was detected in overall population (all p > 0.05). However, increased UC/CD risk for allele 3 was observed in Caucasian population (OR = 1.27, 95% CI = 1.08~1.50, p = 0.04), whereas decreased UC/CD risk was detected in non-Caucasian population (OR = 0.72, 95% CI = 0.60~0.87, p < 0.001), under "allele 3 vs. other alleles" model. Moreover, a significant increase in CD risk for T carrier frequency of -237 C/T (OR = 0.44, 95% CI, 0.26~0.75, p = 0.003) was detected, but not 274 C/T and 1729+55del4 (TGTG) +/del. The polymorphism of -237 C/T is related to the risk of CD; and the association of allele 3 with UC/CD risk differs in Caucasian and non-Caucasian population, which might be the potential biomarkers for clinical diagnosis of UC/CD.

Prevention of urinary tract infections in palliative radiation for vertebral metastasis and spinal compression: A pilot study in 71 patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manas, Ana; Glaria, Luis; Pena, Carmen

2006-03-01

Purpose: To assess the impact of bladder instillations of hyaluronic acid (HA) on the prevalence of urinary tract infection (UTI) in patients receiving emergency radiotherapy for metastatic spinal cord compression. Methods and Materials: Patients were recruited consecutively at one center and assigned to usual care (UC) (n = 34, mean age 62.2 years) or UC with once-weekly HA instillation (UC + HA) (Cystistat: 40 mg in 50 mL phosphate-buffered saline) (n = 37; mean age, 63.1 years). All patients had an indwelling catheter and received radiotherapy. UTI status was assessed at baseline and during hospitalization. Results: At baseline, patient groupsmore » were comparable, except for the prevalence of UTI at baseline, which was 11.8% and 0% in the UC and UC + HA patients, respectively (p = 0.0477). During hospitalization, 76.5% (vs. 11.8% at baseline, p < 0.0001) of the UC patients had a UTI compared with 13.5% (vs. 0% at baseline, p = 0.0541) of the UC + HA patients (p < 0.0001). Both groups were hospitalized for similar periods (19.8 days [UC] vs. 18.5 days, p = 0.4769) and received equivalent radiotherapy sessions (4.6 [UC] vs. 5.8 sessions, p = 0.2368). Conclusions: Patients receiving UC + HA had a 5.7-fold decrease in UTI prevalence over the hospitalization period compared to UC patients, suggesting that bladder instillations of HA effectively prevent UTI in patients with indwelling catheters receiving radiotherapy for nerve compression.« less

Evaluation of enterochromaffin cells and melatonin secretion exponents in ulcerative colitis

PubMed Central

Chojnacki, Cezary; Wiśniewska-Jarosińska, Maria; Kulig, Grażyna; Majsterek, Ireneusz; Reiter, Russel J; Chojnacki, Jan

2013-01-01

AIM: To study an assessment of the number of enterochromaffin cells and expression of hydroxyindole-O-methyltransferase in colonic mucosa and urine excretion of 6-sulfatoxymelatonin in patients with ulcerative colitis. METHODS: The study included 30 healthy subjects (group I-C), 30 patients with ulcerative proctitis [group II-ulcerative proctitis (UP)] and 30 patients with ulcerative colitis [group III-ulcerative colitis (UC)] in acute phases of these diseases. The number of enterochromaffin cells (EC) was estimated in rectal and colonic mucosa. Bioptates were assembled from many different parts of the large intestine. Immunorective cells collected from various parts of the colon were counted according to the Eurovision DAKO (Dako A/S, Copenhagen, Denmark) System in the range of 10 fields in each bioptate at × 200 magnification. The level of mRNA expression of hydroxyindole-O-methyltransferase (HIOMT) in colonic mucosa was estimated with RT-PCR. Urine 6-sulfatoxymelatonin (6-HMS) excretion was determined immunoenzymatically using an IBL (IBL International GmbH, Hamburg, Germany) kit (RE 54031). RESULTS: The number of EC cells in healthy subjects (C) was 132.40 ± 31.26. In patients of group II (UP) and group III (UC) the number of these cells was higher - 225.40 ± 37.35 (P < 0.001) and - 225.24 ± 40.50 (P < 0.001) respectively. Similar differences were related to HIOMT expression, which was 1.04 ± 0.36 in group C, 1.56 ± 0.56 (P < 0.01) in group UP and 2.00 ± 0.35 (P < 0.001) in group UC. Twenty-four hour 6-HMS urinary excretion was as follows: C - 16.32 ± 4.95 μg/24 h, UP - 26.30 ± 7.29 μg/24 h (P < 0.01), UC - 42.30 ± 12.56 μg/24h (P < 0.001). A correlation between number of EC cells and 6-HMS excretion was noted in all groups: r = 0.766 in patients with UP, r = 0.703 with UC and r = 0.8551 in the control group; the correlation between the results is statistically significant. CONCLUSION: In the acute phases of both UP and UC, proliferation of EC cells and high expression of HIOMT and urine excretion of 6-HMS is noted. These changes may represent a beneficial response in the anti-inflammatory and defense mechanism. PMID:23801861

Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies

PubMed Central

Sommer, Breann C.; Dhawan, Deepika; Ratliff, Timothy L.; Knapp, Deborah W.

2018-01-01

The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials. The animal model(s) should possess key features that dictate success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). While it may not be possible to create these collective features in experimental models, these features are present in naturally-occurring InvUC in pet dogs. Naturally occurring canine InvUC closely mimics muscle-invasive bladder cancer in humans in regards to cellular and molecular features, molecular subtypes, biological behavior (sites and frequency of metastasis), and response to therapy. Clinical treatment trials in pet dogs with InvUC are considered a win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. This review will provide an overview of canine InvUC, the similarities to the human condition, and the potential for dogs with InvUC to serve as a model to predict the outcomes of targeted therapy and immunotherapy in humans. PMID:29732386

Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies.

PubMed

Sommer, Breann C; Dhawan, Deepika; Ratliff, Timothy L; Knapp, Deborah W

2018-04-26

The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials. The animal model(s) should possess key features that dictate success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). While it may not be possible to create these collective features in experimental models, these features are present in naturally-occurring InvUC in pet dogs. Naturally occurring canine InvUC closely mimics muscle-invasive bladder cancer in humans in regards to cellular and molecular features, molecular subtypes, biological behavior (sites and frequency of metastasis), and response to therapy. Clinical treatment trials in pet dogs with InvUC are considered a win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. This review will provide an overview of canine InvUC, the similarities to the human condition, and the potential for dogs with InvUC to serve as a model to predict the outcomes of targeted therapy and immunotherapy in humans.

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

PubMed

Ng, Siew C; Tang, Whitney; Leong, Rupert W; Chen, Minhu; Ko, Yanna; Studd, Corrie; Niewiadomski, Ola; Bell, Sally; Kamm, Michael A; de Silva, H J; Kasturiratne, Anuradhani; Senanayake, Yasith Udara; Ooi, Choon Jin; Ling, Khoon-Lin; Ong, David; Goh, Khean Lee; Hilmi, Ida; Ouyang, Qin; Wang, Yu-Fang; Hu, PinJin; Zhu, Zhenhua; Zeng, Zhirong; Wu, Kaichun; Wang, Xin; Xia, Bing; Li, Jin; Pisespongsa, Pises; Manatsathit, Sathaporn; Aniwan, Satimai; Simadibrata, Marcellus; Abdullah, Murdani; Tsang, Steve W C; Wong, Tai Chiu; Hui, Aric J; Chow, Chung Mo; Yu, Hon Ho; Li, Mo Fong; Ng, Ka Kei; Ching, Jessica; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

2015-07-01

The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. 442 incident cases (186 Crohn's disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases

PubMed Central

Jakubowska, Katarzyna; Pryczynicz, Anna; Iwanowicz, Piotr; Niewiński, Andrzej; Maciorkowska, Elżbieta; Hapanowicz, Jerzy; Jagodzińska, Dorota; Kemona, Andrzej; Guzińska-Ustymowicz, Katarzyna

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression. PMID:27034654

Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases.

PubMed

Jakubowska, Katarzyna; Pryczynicz, Anna; Iwanowicz, Piotr; Niewiński, Andrzej; Maciorkowska, Elżbieta; Hapanowicz, Jerzy; Jagodzińska, Dorota; Kemona, Andrzej; Guzińska-Ustymowicz, Katarzyna

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

Histological and immunological features of appendix in patients with ulcerative colitis.

PubMed

Jo, Yukihiko; Matsumoto, Takayuki; Yada, Shinichiro; Nakamura, Shotaro; Yao, Takashi; Hotokezaka, Masayuki; Mibu, Ryuichi; Iida, Mitsuo

2003-01-01

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Bactericidal/permeability increasing protein gene polymorphism and inflammatory bowel diseases: meta-analysis of five case-control studies.

PubMed

Fan, Lijuan; Fu, Guoning; Ding, Yuanyuan; Lv, Peng; Li, Hongyun

2017-03-01

Bactericidal/permeability increasing protein (BPI) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between BPI gene polymorphisms and the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and Cochrane library databases were identified. Ten studies (five CD and five UC) published in five papers were included in this meta-analysis. G645A polymorphism was associated with a decreased risk of UC in allele model, dominant model, and homozygous model. Our data suggested that BPI G645A polymorphism was associated with a decreased risk of UC; the BPI G645A polymorphism was not associated with the risk of CD.

Animal models of ulcerative colitis and their application in drug research

PubMed Central

Low, Daren; Nguyen, Deanna D; Mizoguchi, Emiko

2013-01-01

The specific pathogenesis underlying inflammatory bowel disease is complex, and it is even more difficult to decipher the pathophysiology to explain for the similarities and differences between two of its major subtypes, Crohn’s disease and ulcerative colitis (UC). Animal models are indispensable to pry into mechanistic details that will facilitate better preclinical drug/therapy design to target specific components involved in the disease pathogenesis. This review focuses on common animal models that are particularly useful for the study of UC and its therapeutic strategy. Recent reports of the latest compounds, therapeutic strategies, and approaches tested on UC animal models are also discussed. PMID:24250223

Decreased Levels of Circulating Carboxylated Osteocalcin in Children with Low Energy Fractures: A Pilot Study.

PubMed

Popko, Janusz; Karpiński, Michał; Chojnowska, Sylwia; Maresz, Katarzyna; Milewski, Robert; Badmaev, Vladimir; Schurgers, Leon J

2018-06-06

In the past decades, an increased interest in the roles of vitamin D and K has become evident, in particular in relation to bone health and prevention of bone fractures. The aim of the current study was to evaluate vitamin D and K status in children with low-energy fractures and in children without fractures. The study group of 20 children (14 boys, 6 girls) aged 5 to 15 years old, with radiologically confirmed low-energy fractures was compared with the control group of 19 healthy children (9 boys, 10 girls), aged 7 to 17 years old, without fractures. Total vitamin D (25(OH)D3 plus 25(OH)D2), calcium, BALP (bone alkaline phosphatase), NTx (N-terminal telopeptide), and uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) serum concentrations were evaluated. Ratio of serum uncarboxylated osteocalcin to serum carboxylated osteocalcin ucOC:cOC (UCR) was used as an indicator of bone vitamin K status. Logistic regression models were created to establish UCR influence for odds ratio of low-energy fractures in both groups. There were no statistically significant differences in the serum calcium, NTx, BALP, or total vitamin D levels between the two groups. There was, however, a statistically significant difference in the UCR ratio. The median UCR in the fracture group was 0.471 compared with the control group value of 0.245 ( p < 0.0001). In the logistic regression analysis, odds ratio of low-energy fractures for UCR was calculated, with an increased risk of fractures by some 78.3 times. In this pilot study, better vitamin K status expressed as the ratio of ucOC:cOC-UCR—is positively and statistically significantly correlated with lower rate of low-energy fracture incidence.

Plant-based ointments versus usual care in the management of chronic skin diseases: a comparative analysis on outcome and safety.

PubMed

Jong, Miek C; Ermuth, Ulrike; Augustin, Matthias

2013-10-01

To assess the outcome and safety of plant-based ointments versus usual care in the management of chronic skin diseases. Prospective mono-centric comparative analysis. Patients were recruited at an outpatient dermatology clinic and treated with plant-based ointments or care as usual. Main outcome criterion was the response rate, defined as the proportion of patients experiencing 'complete recovery' or 'major improvement' at 6, 12 and 24 months. Secondary outcome criteria were quality of life (SF-12 and EQ-5D), patient satisfaction and safety of treatment. A total of 112 patients with chronic skin diseases were evaluated of which 44 were treated with plant-based ointments (PO) and 68 received usual care (UC). The majority of patients suffered from psoriasis (PO: 50%; UC: 56%) or eczema (PO: 41%; UC: 32%) and were treated with homoeopathic topical ointments containing mahonia or cardiospermum or usual care creams containing calcipotriene and corticosteroids. The only significant difference in baseline status between the two groups was in disease severity score (PO: 1.8±0.7 versus UC: 2.4±0.8, p=0.0004). After two years, the main outcome of responders to treatment was 52.3% (95%-CI: 36.1-64.9) in the ointment and 41.2% (95%-CI: 20.4-42.2) in the UC group. Change in SF-12 (2 years compared to baseline), adjusted for baseline disease severity, was not significantly different between both groups; PO: 5.4 (95%-CI: 3.4-7.3) versus UC: 3.2 (95%-CI: 1.5-4.9). The adjusted EQ-5D was found to be significantly different between the two groups after two years, in favour of the ointment group; PO: 0.113 (95%-CI: 0.052-0.174) and UC: -0.008 (95%-CI: -0.055-0.038). Other secondary outcome parameters such as patient satisfaction and number of adverse drug reactions were comparable. The outcome of this study suggests at least therapeutic equivalence between plant-based ointments and usual care management of chronic skin diseases. As this non-randomised study was open to selection and other bias, further rigorous studies are needed to demonstrate the effectiveness of these topical products. Copyright © 2013 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delaney, Alexander R., E-mail: a.delaney@vumc.nl; Tol, Jim P.; Dahele, Max

Purpose: RapidPlan, a commercial knowledge-based planning solution, uses a model library containing the geometry and associated dosimetry of existing plans. This model predicts achievable dosimetry for prospective patients that can be used to guide plan optimization. However, it is unknown how suboptimal model plans (outliers) influence the predictions or resulting plans. We investigated the effect of, first, removing outliers from the model (cleaning it) and subsequently adding deliberate dosimetric outliers. Methods and Materials: Clinical plans from 70 head and neck cancer patients comprised the uncleaned (UC) Model{sub UC}, from which outliers were cleaned (C) to create Model{sub C}. The lastmore » 5 to 40 patients of Model{sub C} were replanned with no attempt to spare the salivary glands. These substantial dosimetric outliers were reintroduced to the model in increments of 5, creating Model{sub 5} to Model{sub 40} (Model{sub 5-40}). These models were used to create plans for a 10-patient evaluation group. Plans from Model{sub UC} and Model{sub C}, and Model{sub C} and Model{sub 5-40} were compared on the basis of boost (B) and elective (E) target volume homogeneity indexes (HI{sub B}/HI{sub E}) and mean doses to oral cavity, composite salivary glands (comp{sub sal}) and swallowing (comp{sub swal}) structures. Results: On average, outlier removal (Model{sub C} vs Model{sub UC}) had minimal effects on HI{sub B}/HI{sub E} (0%-0.4%) and sparing of organs at risk (mean dose difference to oral cavity and comp{sub sal}/comp{sub swal} were ≤0.4 Gy). Model{sub 5-10} marginally improved comp{sub sal} sparing, whereas adding a larger number of outliers (Model{sub 20-40}) led to deteriorations in comp{sub sal} up to 3.9 Gy, on average. These increases are modest compared to the 14.9 Gy dose increases in the added outlier plans, due to the placement of optimization objectives below the inferior boundary of the dose-volume histogram-predicted range. Conclusions: Overall, dosimetric outlier removal from or addition of 5 to 10 outliers to a 70-patient model had marginal effects on resulting plan quality. Although the addition of >20 outliers deteriorated plan quality, the effect was modest. In this study, RapidPlan demonstrated robustness for moderate proportions of salivary gland dosimetric outliers.« less

Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats

PubMed Central

Tanideh, Nader; Jamshidzadeh, Akram; Sepehrimanesh, Masood; Hosseinzadeh, Masood; Koohi-Hosseinabadi, Omid; Najibi, Asma; Raam, Mozhdeh; Daneshi, Sajad; Asadi-Yousefabad, Seyedeh-Leili

2016-01-01

Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats. PMID:26831607

Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder.

PubMed

Brar, Jaspreet S; Ganguli, Rohan; Pandina, Gahan; Turkoz, Ibrahim; Berry, Sally; Mahmoud, Ramy

2005-02-01

Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). BT may be an effective method for weight reduction in patients with chronic psychotic illness.

Impact of inflammatory bowel disease on pubertal growth.

PubMed

Mason, A; Malik, S; Russell, R K; Bishop, J; McGrogan, P; Ahmed, S F

2011-01-01

Puberty is thought to be commonly affected in adolescents with inflammatory bowel disease (IBD). To determine the impact of Crohn's disease (CD) and ulcerative colitis (UC) on the pubertal growth spurt. Retrospective study of 30 boys with CD (CD-M), 11 girls with CD (CD-F), 14 boys with UC (UC-M) and 12 girls with UC (UC-F). Pubertal growth was assessed by calculating peak height velocity SDS (PHV SDS), height SDS at diagnosis (Ht(Diag)) and height SDS at PHV (Ht(PHV)) and age at PHV (Age(PHV)). Systemic markers of disease activity were also collected. Altered parameters of pubertal growth were observed in the CD groups compared to the normal population: in the CD-M group, median Ht(Diag) was -0.56 (p = 0.001) and median Age(PHV) was 14.45 years (p = 0.004), and in the CD-F group, median Ht(Diag) was -1.14 (p = 0.007) and Ht(PHV) was -0.79 (p = 0.039). Individually, 8/30 CD-M cases had one or more parameter affected: 2 boys had Ht(Diag )<-2, 3 boys had Ht(PHV) <-2, 2 boys had an Age(PHV) >2 years above population mean, and 2 boys had a PHV SDS <-2. In the whole group, Age(PHV) showed an association with erythrocyte sedimentation rate (r = 0.4; p = 0.005) and an inverse association with BMI (r = 0.4; p = 0.001). Disorders of pubertal growth are more likely to occur in CD and, particularly, in boys. Copyright © 2011 S. Karger AG, Basel.

Effect of Yoga-Based Intervention in Patients with Inflammatory Bowel Disease.

PubMed

Sharma, Purnima; Poojary, Gopal; Dwivedi, Sada Nand; Deepak, Kishore Kumar

2015-01-01

Inflammatory bowel disease (IBD) is a chronic illness characterized by gross inflammation in the gastrointestinal tract that can result in symptoms such as abdominal pain, cramping, diarrhea, and bloody stools. IBD is believed to be influenced by psychological factors such as stress and anxiety. Therefore, a yoga intervention that reduces stress and anxiety may be an effective complementary treatment for these disorders. A total of 100 IBD patients [ulcerative colitis (UC) n = 60 and Crohn's disease (CD) n = 40] during the clinical remission phase of disease were included in the study. These patients were allocated randomly to either the yoga group that underwent an 8-week yoga intervention (physical postures, pranayama, and meditation) 1- hour/day in addition to standard medical therapy (UC, n = 30; CD, n = 20) or the control group (UC, n = 30; CD n = 20), which continued with standard medical therapy alone. The main outcome measures were cardiovascular autonomic functions, serum eosinophilic cationic protein, interleukin- 2 soluble receptors, Speilberger's State Trait Anxiety Inventory (STAI) scores, and clinical symptoms. Before the intervention, all the outcome measures were comparable in the two groups. After the 8-week yoga intervention, fewer UC patients reported arthralgia. The number of patients reporting intestinal colic pain in the control group was higher. State and trait anxiety levels were significantly reduced in patients with UC. However, no significant changes were observed in cardiovascular autonomic functions, eosinophilic cationic proteins, or interleukin-2 soluble receptors. A simplified yoga-based regimen is a safe and effective complementary clinical treatment modality for patients with inflammatory bowel disease during the clinical remission phase.

Economic evaluation of a disease management program for chronic obstructive pulmonary disease.

PubMed

Dewan, Naresh A; Rice, Kathryn L; Caldwell, Michael; Hilleman, Daniel E

2011-06-01

The data on cost savings with disease management (DM) in chronic obstructive pulmonary disease (COPD) is limited. A multicomponent DM program in COPD has recently shown in a large randomized controlled trial to reduce hospitalizations and emergency department visits compared to usual care (UC). The objectives of this study were to determine the cost of implementing the DM program and its impact on healthcare resource utilization costs compared to UC in high-risk COPD patients. This study was a post-hoc economic analysis of a multicenter randomized, adjudicator-blinded, controlled, 1-year trial comparing DM and UC at 5 Midwest region Department of Veterans Affairs (VA) medical centers. Health-care costs (hospitalizations, ED visits, respiratory medications, and the cost of the DM intervention) were compared in the COPD DM intervention and UC groups. The composite outcome for all hospitalizations or ED visits were 27% lower in the DM group (123.8 mean events per 100 patient-years) compared to the UC group (170.5 mean events per 100 patient-years) (rate ratio 0.73; 0.56-0.90; p < 0.003). The cost of the DM intervention was $241,620 or $650 per patient. The total mean ± SD per patient cost that included the cost of DM in the DM group was 4491 ± 4678 compared to $5084 ± 5060 representing a $593 per patient cost savings for the DM program. The DM intervention program in this study was unique for producing an average cost savings of $593 per patient after paying for the cost of DM intervention.

Impact of physical activity on fatigue and quality of life in people with advanced lung cancer: a randomized controlled trial.

PubMed

Dhillon, H M; Bell, M L; van der Ploeg, H P; Turner, J D; Kabourakis, M; Spencer, L; Lewis, C; Hui, R; Blinman, P; Clarke, S J; Boyer, M J; Vardy, J L

2017-08-01

Physical activity (PA) improves fatigue and quality of life (QOL) in cancer survivors. Our aim was to assess whether a 2-month PA intervention improves fatigue and QOL for people with advanced lung cancer. Participants with advanced lung cancer, Eastern Cooperative Oncology Group performance status (PS) ≤2, >6 months life expectancy, and ability to complete six-min walk test, were stratified (disease stage, PS 0-1 versus 2, centre) and randomized (1:1) in an open-label study to usual care (UC) (nutrition and PA education materials) or experimental intervention (EX): UC plus 2-month supervised weekly PA and behaviour change sessions. Assessments occurred at baseline, 2, 4, and 6 months. The primary endpoint was fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire] at 2 months. The study was designed to detect a difference in mean FACT-F subscale score of 6. Analysis was intention-to-treat using linear mixed models. We recruited 112 patients: 56 (50.4%) were randomized to EX, 55(49.5%) to UC; 1 ineligible. Male 55%; median age 64 years (34-80); 106 (96%) non-small cell lung cancer; 106 (95.5%) stage IV. At 2, 4 and 6 months, 90, 73 and 62 participants were assessed, respectively, with no difference in attrition between groups. There were no significant differences in fatigue between the groups at 2, 4 or 6 months: mean scores at 2 months EX 37.5, UC 36.4 (difference 1.2, 95% CI - 3.5, 5.8, P = 0.62). There were no significant differences in QOL, symptoms, physical or functional status, or survival. Adherence to the intervention was good but the intervention group did not increase their PA enough compared to the control group, and no difference was seen in fatigue or QOL. Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Results of a prospective randomized control trial comparing hydrophilic to uncoated catheters in children with neurogenic bladder.

PubMed

DeFoor, William; Reddy, Pramod; Reed, Melissa; VanderBrink, Brian; Jackson, Elizabeth; Zhang, Bin; Denlinger, Julie; Noh, Paul; Minevich, Eugene; Sheldon, Curtis

2017-08-01

Children with neurogenic bladder (NGB) often require a lifetime of clean intermittent catheterization (CIC), typically using uncoated catheters (UCs). Hydrophilic catheters (HCs) have lower friction than UCs with reported less damage to the urethra. The purpose of this study is to compare outcomes between these catheters. An investigator-initiated, prospective, randomized clinical trial was conducted to compare HCs versus UCs. Children aged 2-17 years with NGB on CIC were enrolled for 1 year. Block randomization was used. Dexterity scores were obtained in those who perform self-catheterization. Outcomes were UTI, difficulty passing the catheter, urethral injury, and patient satisfaction. Demographic data is presented in the Table. Seventy-eight patients were enrolled. Age and gender were similar between the groups. Fifteen patients in each group performed CIC via an abdominal wall stoma. Eight and 15 patients withdrew from the UC and HC groups, respectively. The HC group overall had more problems with the catheter, mainly difficulty with handling. There were no differences for passing the catheter, pain, hematuria, or urethral injuries. There were two urinary tract infections (UTIs) in two HC patients and 17 UTIs in seven UC patients (p = 0.003). Patients with UTIs in the HC group went from 16% in the previous year to 5% during the study. Three children in the HC group had three or more UTIs in the year before enrollment and none during the study. The patients that completed the study with HC were overall satisfied and many requested to continue with the HC. HCs may decrease the risk of UTI in children with NGB. Urethral complications were low in both groups. Most HC patients were pleased but some found the slippery coating difficult to handle. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Interleukin-23 receptor genetic polymorphisms and ulcerative colitis susceptibility: A meta-analysis.

PubMed

Liu, Min; Zhu, Wenqian; Wang, Jun; Zhang, Jixiang; Guo, Xufeng; Wang, Jing; Song, Jia; Dong, Weiguo

2015-09-01

The interleukin-23 receptor (IL-23R) polymorphism has been implicated in susceptibility to ulcerative colitis (UC), but the results remain inconclusive. This study was designed to evaluate whether IL-23R polymorphisms were associated with UC susceptibility. CNKI, WanFang Data, PubMed, MEDLINE, Web of Science, Google Scholar, EBSCO, CBM database and EMBASE were searched until 31 June 2014 for eligible studies on eight IL-23R polymorphisms: rs11209026, rs7517847, rs1209032, rs2201841, rs1343151, rs1088967, rs1495965 and rs1004819. Meta-analysis from all eligible case-control studies was performed to assess the purported associations. Meta-analysis was performed by using the RevMan 5.2 software and STATA package version 12.0. Sixteen studies with 5438 cases and 7380 controls were included. Overall, our analysis found that variant minor alleles for single nucleotide polymorphisms (SNPs) rs11209026 (Arg381Gln) (dominant model: GG+TG vs. TT, P=0.02, OR=0.71, 95%CI: 0.53-0.94); rs7517847 (recessive model: GG vs. TT, P=0.04, OR=0.80, 95%CI: 0.65-0.99) and rs11209032 [dominant model: GA+AA vs. GG (P=0.04, OR=1.31, 95% CI: 1.01-1.26); AA vs. GG: (P=0.04, OR=1.21, 95% CI: 1.01-1.45)] of IL-23R were associated with UC risk. In stratification analysis by ethnicity, we observed that the rs11209026 and rs7517847 polymorphism of IL-23R could protect against development of UC among Caucasian populations [rs11209026: dominant model (P=0.01, OR=0.69, 95%CI: 0.52-0.92); rs7517847: GG vs. TT (P=0.002, OR=0.69, 95%CI: 0.54-0.87); recessive model (P=0.004, OR=0.73, 95% CI: 0.59-0.90)]; the rs11209032 were associated with a greater risk for UC in Caucasian populations [dominant model (P=0.04, OR=1.13, 95%CI: 1.00-1.26)]; the rs1088967 were associated with a lower risk for UC among Asian populations [dominant model (P=0.04, OR=0.73, 95%CI: 0.54-0.99)]. Moreover, meta-analysis revealed no association between the four alleles of the rs2201841, rs1004819, rs1495965 and rs1343151 polymorphisms and the risk of developing UC in Caucasian and Asian populations. Our meta-analysis supports that two polymorphisms (rs11209026 and rs7517847) in the IL-23 gene may be considered to be protective factors against developing UC among Caucasian populations; while the rs11209032 polymorphisms may increase the risk of UC among Caucasian populations; furthermore, the rs1088967 polymorphisms in the IL-23 gene may be considered to be protective factors against developing UC among Asian populations. Further large case-control studies especially concerning ethnicity differences and genotype-phenotype interaction should be performed to clarify possible roles of IL-23R in UC. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

PubMed Central

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-01-01

Objective Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. Design We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Results Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn’s disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. Conclusions α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. PMID:26209553

Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats.

PubMed

Wang, L; Li, P; Tian, Y; Li, Z; Lian, C; Ou, Q; Jin, C; Gao, F; Xu, J-Y; Wang, J; Wang, F; Zhang, J; Zhang, J; Li, W; Tian, H; Lu, L; Xu, G-T

2017-01-01

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A case-control study of the association between ulcerative colitis and hyperthyroidism in an Asian population.

PubMed

Tsai, Ming-Chieh; Lin, Herng-Ching; Lee, Cha-Ze

2017-06-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P<.001). A conditional logistic regression showed that the OR of prior hyperthyroidism was 1.57 (95% CI=1.24-1.98) compared to controls. Similarly, after adjusting for monthly income, geographic location and urbanization level, cases were still more likely to have previously been diagnosed with hyperthyroidism than controls (OR=1.61, 95% CI=1.27-2.05). Furthermore, we analysed the ORs of prior hyperthyroidism between cases and controls according to age group. We found that of the youngest group of sampled patients (18-39 years), cases had the greatest adjusted OR for having previously been diagnosed with hyperthyroidism than controls (OR=1.98, 95% CI=1.04-3.79). This study demonstrated an association between UC and hyperthyroidism. © 2017 John Wiley & Sons Ltd.

The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission.

PubMed

Jonefjäll, Börje; Simrén, Magnus; Öhman, Lena; Lasson, Anders; Svedlund, Jan; Strid, Hans

2015-09-01

Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR-IBS). Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Nutritional status of children with inflammatory bowel disease in Saudi Arabia.

PubMed

El Mouzan, Mohammad Issa; Al Edreesi, Mohammed Hadi; Al-Hussaini, Abdulrahman Abdullah; Saadah, Omar Ibrahim; Al Qourain, Abdulaziz Abdullatif; Al Mofarreh, Mohammad Abdullah; Al Saleem, Khalid Abdulrahman

2016-02-07

To assess the prevalence of nutritional disorders in children with inflammatory bowel disease (IBD) in Saudi Arabia. The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn's disease (CD) and ulcerative colitis (UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index (BMI) of each child [weight (kg)/height(2) (m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and < -2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older. There were 374 children from 0.33 to 17 years of age, including 119 (32%) children with UC and 255 (68%) with CD. All of the children were Saudi nationals, and 68 (57%) of the UC and 150 (59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30 (25%) patients with UC and 99 (39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC (P = 0.037) only in the age group of 10-17 years (P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years (P = 0.020). A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care.

Nutritional status of children with inflammatory bowel disease in Saudi Arabia

PubMed Central

El Mouzan, Mohammad Issa; Al Edreesi, Mohammed Hadi; Al-Hussaini, Abdulrahman Abdullah; Saadah, Omar Ibrahim; Al Qourain, Abdulaziz Abdullatif; Al Mofarreh, Mohammad Abdullah; Al Saleem, Khalid Abdulrahman

2016-01-01

AIM: To assess the prevalence of nutritional disorders in children with inflammatory bowel disease (IBD) in Saudi Arabia. METHODS: The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn’s disease (CD) and ulcerative colitis (UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index (BMI) of each child [weight (kg)/height2 (m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and < -2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older. RESULTS: There were 374 children from 0.33 to 17 years of age, including 119 (32%) children with UC and 255 (68%) with CD. All of the children were Saudi nationals, and 68 (57%) of the UC and 150 (59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30 (25%) patients with UC and 99 (39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC (P = 0.037) only in the age group of 10-17 years (P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years (P = 0.020). CONCLUSION: A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care. PMID:26855544

Serology of Patients with Ulcerative Colitis After Pouch Surgery Is More Comparable with that of Patients with Crohn's Disease.

PubMed

Goren, Idan; Yahav, Lior; Tulchinsky, Hagit; Dotan, Iris

2015-10-01

The serologic status of patients with ulcerative colitis (UC) who develop postoperative pouchitis was compared with that of patients with Crohn's disease (CD) and unoperated patients with UC. Pouch patients were stratified into normal pouch, acute/recurrent acute pouchitis, and chronic pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA, and AMCA, respectively]) were detected and correlated with type of inflammatory bowel disease and pouch behavior. A total of 501 patients with inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6% CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and 16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001 for all). ALCA and ASCA were more prevalent in patients with CD than unoperated UC and UC-pouch patients. A longer interval since pouch surgery was associated with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal pouch, respectively, P = 0.01 for all. The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC-pouch patients, suggesting that pouch surgery may trigger differential immune responses to glycans. The finding that the serology of UC-pouch patients shares similarities with that of patients with CD supports the notion that those 2 inflammatory bowel diseases share a common pathogenic pathway.

[Multicentric prospective randomized and controlled study assessing effectiveness of intravaginal electrostimulation at home compared to usual care in female patients with urinary incontinence and prior perineal reeducation].

PubMed

Lopès, P; Rimbault, F; Scheffler, M; André, C; Cappelletti, M-C; Marès, P

2014-11-01

In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported as worsened in 16.5% of the UC group. Using GYNEFFIK(®) favorably impacts quality of life, particularly physical activity and vitality and decreases emotional consequences of UI (i.e. anxiety and depression score as assessed by HAD scale). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Extracellular Vesicles Released from Human Umbilical Cord-Derived Mesenchymal Stromal Cells Prevent Life-Threatening Acute Graft-Versus-Host Disease in a Mouse Model of Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Wang, Li; Gu, Zhenyang; Zhao, Xiaoli; Yang, Nan; Wang, Feiyan; Deng, Ailing; Zhao, Shasha; Luo, Lan; Wei, Huaping; Guan, Lixun; Gao, Zhe; Li, Yonghui; Wang, Lili; Liu, Daihong; Gao, Chunji

2016-12-15

Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord-derived MSCs (hUC-MSC-EVs) could prevent aGVHD in a mouse model of allo-HSCT. hUC-MSC-EVs were intravenously administered to recipient mice on days 0 and 7 after allo-HSCT, and the prophylactic effects of hUC-MSC-EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival. We evaluated the effects of hUC-MSC-EVs on immune cells and inflammatory cytokines by flow cytometry and ProcartaPlex™ Multiplex Immunoassays, respectively. The in vitro effects of hUC-MSC-EVs were determined by mitogen-induced proliferation assays. hUC-MSC-EVs alleviated the in vivo manifestations of aGVHD and the associated histologic changes and significantly reduced the mortality of the recipient mice. Recipients treated with hUC-MSC-EVs had significantly lower frequencies and absolute numbers of CD3 + CD8 + T cells; reduced serum levels of IL-2, TNF-α, and IFN-γ; a higher ratio of CD3 + CD4 + and CD3 + CD8 + T cells; and higher serum levels of IL-10. An in vitro experiment demonstrated that hUC-MSC-EVs inhibited the mitogen-induced proliferation of splenocytes in a dose-dependent manner, and the cytokine changes were similar to those observed in vivo. This study indicated that hUC-MSC-EVs can prevent life-threatening aGVHD by modulating immune responses. These data provide the first evidence that hUC-MSC-EVs represent an ideal alternative in the prophylaxis of aGVHD after allo-HSCT.

Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial

PubMed Central

Zhang, Jian; Lv, Samei; Liu, Xiaojing; Song, Bin; Shi, Liping

2018-01-01

Background/Aims Stem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn’s disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD. Methods Eighty-two patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months were included in this study. Forty-one patients were randomly selected to receive a total of four peripheral intravenous infusions of 1×106 UC-MSCs/kg, with one infusion per week. Patients were followed up for 12 months. The Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), and corticosteroid dosage were assessed. Results Twelve months after treatment, the CDAI, HBI, and corticosteroid dosage had decreased by 62.5±23.2, 3.4±1.2, and 4.2±0.84 mg/day, respectively, in the UC-MSC group and by 23.6±12.4, 1.2±0.58, and 1.2±0.35 mg/day, respectively, in the control group (p<0.01, p<0.05, and p<0.05 for UC-MSC vs control, respectively). Four patients developed a fever after cell infusion. No serious adverse events were observed. Conclusions UC-MSCs were effective in the treatment of CD and produced mild side effects. PMID:28873511

A randomized, controlled study to evaluate the role of an in-home asthma disease management program provided by respiratory therapists in improving outcomes and reducing the cost of care.

PubMed

Shelledy, David C; Legrand, Terry S; Gardner, Donna D; Peters, Jay I

2009-03-01

Asthma management programs (AMP) may reduce costs and improve outcomes in patients with moderate to severe asthma. However, it is not known which personnel are best able to deliver such interventions and what settings are most effective. The purpose of this study was to compare the effects of an in-home AMP provided by respiratory therapists (RTs) to an AMP provided by nurses (RNs) and to usual care (UC) provided in physician offices or clinics. Subjects (age 18-64) who had been admitted to the emergency department (ED) or hospital for acute asthma exacerbation were randomized to three groups: AMP-RT, AMP-RN or UC. The AMP groups received five (5) weekly home visits to provide assessment and instruction; the UC group was instructed to return to their physician for routine follow-up. Outcomes assessed at 6 months included hospitalizations, in patient days, hospitalization cost, ED visits and cost, clinic visits, pulmonary function, symptoms, health related quality of life (HRQOL), asthma episode self-management score (AESM), environmental assessment, and patient satisfaction (PS). Variables were compared using ANOVA with a Neuman-Keuls follow-up for multiple comparisons using an intent-to-treat approach. Upon enrollment, (n = 159) there were no differences (p > .05) between groups for age, gender, pulmonary function or HRQOL (SF-36 and St. Georges Respiratory Questionnaire - SGRQ). At 6 months, both AMP groups (AMP-RN n = 54; AMP-RT n = 46) had significantly fewer (p < 0.05) hospitalizations and in-patient days, lower hospitalization costs, and greater HRQOL physical component summary change scores (PCS) and PS than UC (n = 59). AMP-RT also had greater PEFR, SGRQ Total and SGRQ Symptoms change scores when compared to UC and significantly better AESM and PS scores as compared to AMP-RN and UC. An in-home asthma management program can be effectively delivered by respiratory therapists and may reduce hospitalizations, in-patient days, cost and improve measures of HRQOL and PS in a population prone to asthma exacerbation.

Ethnic variations in ulcerative colitis: Experience of an international hospital in Thailand.

PubMed

Permpoon, Vibhakorn; Pongpirul, Krit; Anuras, Sinn

2016-08-06

To investigate the clinical characteristics, treatment, medication use, and treatment response in patients with ulcerative colitis (UC) across ethnic groups. This study retrospectively analyzed medical records of all 268465 patients who visited the Bumrungrad International Digestive Disease Center during 2005-2010. The demographics, clinical characteristics, medication use, results of investigations, and medical and surgical management for patients with UC were evaluated. Evaluation included sigmoidoscopy and colonoscopy performed in compliance with the American Society of Gastrointestinal Endoscopy practice guidelines. Patient ethnicities were categorized into seven groups: Thai, Oriental, South Asian (SA), Middle Eastern (ME), Caucasian, African, and Hispanic. UC pathological severity was classified into inactive, mild, moderate, and severe. Associations between categorical variables were analyzed using the χ(2) or Fischer's exact test. Associations between categorical and interval variables were analyzed using Student's t-test and/or analysis of covariance. UC was diagnosed in 371 of the 268465 patients: male 56.33%; ME 42%, Caucasian 23%, and Thai 19%. Annual incidence of UC was 82 cases per 100000 with wide ethnic variation, ranging from 29 to 206 cases per 100000 in Oriental and ME patients, respectively. Of the patients with UC, 16.71% had severe UC with highest incidence among the patients from ME (20.39%) and lowest among the Caucasian population (11.90%). ME had highest proportion of pancolitis (52.90%), followed by Caucasian (45.35%) and Asian (34.40%). Only 20.93% of Caucasian patients received steroid, compared with 26.40% and 27.10% of Asian and Middle Eastern, respectively (P = 0.732). Overall, 13.72% of UC patients did not respond to steroid therapy, with non-significantly higher proportions of non-responders among Asian and Middle Eastern patients (15.22% and 15.04%, respectively) (P = 0.781). On average, 5.93% underwent surgical management with ethnic variation, ranging from 0% in African to 18% in SA. Cancer was found in three (Thai, ME, and African) cases (0.82 institution-specific incidence). Incidence, symptom duration, pathological severity, clinical manifestations, medication use, treatment response, need for surgical consultation, and cancer incidence of patients with UC potentially vary by ethnicity.

Gender dimorphism and lack of day/night variation or effects of energy deprivation on undercarboxylated osteocalcin levels in humans.

PubMed

Foo, Joo-Pin; Aronis, Konstantinos N; Chamberland, John P; Thakkar, Bindiya; Hamnvik, Ole-Petter; Brinkoetter, Mary; Zaichenko, Lesya; Mantzoros, Christos S

2013-12-01

Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans. Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels. Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic energy deprivation or leptin administrations do not alter ucOC levels. The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported. Copyright © 2013 The Obesity Society.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

PubMed

Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study

PubMed Central

Öhman, Lena; Stotzer, Per-Ove; Isaksson, Stefan; Überbacher, Otto; Ung, Kjell-Arne; Strid, Hans

2015-01-01

Background Targeted therapy, using biomarkers to assess disease activity in ulcerative colitis (UC), has been proposed. Objective The objective of this study was to evaluate whether pharmacological intervention guided by fecal calprotectin (FC) prolongs remission in patients with UC. Methods A total of 91 adults with UC in remission were randomized to an intervention group or a control group. Analysis of FC was performed monthly, during 18 months. A FC value of 300 µg/g was set as the cut-off for intervention, which was a dose escalation of the oral 5-aminosalicylate (5-ASA) agent. The primary study end-point was the number of patients to have relapsed by month 18. Results There were relapses in 18 (35.3%) and 20 (50.0%) patients in the intervention and the control groups, respectively (p = 0.23); and 28 (54.9%) patients in the intervention group and 28 (70.0%) patients in the control group had a FC > 300 µg/g, of which 8 (28.6%) and 16 (57.1%) relapsed, respectively (p < 0.05). Conclusion Active intervention significantly reduced relapse rates, although no significant difference was reached between the groups overall. Thus, FC-levels might be used to identify patients with UC at risk for a flare, and a dose escalation of their 5-ASA agent is a therapeutic option for these patients. PMID:25653861

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

PubMed

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena Y Z; Martin, Patrick

2016-01-01

Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.

LncRNA uc.48+ is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia.

PubMed

Wang, Shouyu; Xu, Hong; Zou, Lifang; Xie, Jinyang; Wu, Hong; Wu, Bing; Yi, Zhihua; Lv, Qiulan; Zhang, Xi; Ying, Mofeng; Liu, Shuangmei; Li, Guilin; Gao, Yun; Xu, Changshui; Zhang, Chunping; Xue, Yun; Liang, Shangdong

2016-03-01

Some long non-coding RNAs (lncRNAs) participate in physiological processes that maintain cellular and tissue homeostasis, and thus, the dysregulated expression of lncRNAs is involved in the onset and progression of many pathological conditions. Research has indicated that the genetic knockout of some lncRNAs in mice resulted in peri- or postnatal lethality or developmental defects. Diabetes mellitus (DM) is a major cause of peripheral neuropathy. Our studies showed that the expression levels of lncRNA uc.48+ in the diabetic rat dorsal root ganglia (DRG) and the DM patients' serum samples were increased. It suggested that lncRNA uc.48+ was involved in the pathophysiological process of DM. The aim of this study was to investigate the effects of lncRNA uc.48+ small interfering RNA (siRNA) on diabetic neuropathic pain (DNP) mediated by the P2X3 receptor in the DRG. The values of the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von Frey test and Hargreaves' test, respectively. The levels of P2X3 protein and messenger RNA (mRNA) in the DRG were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting. The experiments showed that the MWT and TWL values in DM rats were lower than those in the control rats. The MWT and TWL values in DM rats treated with lncRNA uc.48+ siRNA were increased compared to those in DM rats, but there was no significant difference between the DM rat group and the DM + scramble siRNA group. The levels of P2X3 protein and mRNA in the DM DRG were higher than those in the control, while the levels of P2X3 protein and mRNA in the DG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in DM rats. The expression levels of TNF-α in the DRG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in the DM group. The phosphorylation and activation of ERK1/2 in the DM DRG were decreased by uc.48+ siRNA treatment. Therefore, uc.48+ siRNA treatment may alleviate the DNP by inhibiting the excitatory transmission mediated by the P2X3 receptor in DRG.

The use of index tests to determine the mechanical properties of crushed aggregates from Precambrian basement complex rocks, Ado-Ekiti, SW Nigeria

NASA Astrophysics Data System (ADS)

Afolagboye, Lekan Olatayo; Talabi, Abel Ojo; Oyelami, Charles Adebayo

2017-05-01

This study assessed the possibility of using index tests to determine the mechanical properties of crushed aggregates. The aggregates used in this study were derived from major Precambrian basement rocks in Ado-Ekiti, Nigeria. Regression analyses were performed to determine the empirical relations that mechanical properties of the aggregates may have with the point load strength (IS(50)), Schmidt rebound hammer value (SHR) and unconfined compressive strength (UCS) of the rocks. For all the data, strong correlation coefficients were found between IS(50), SHR, UCS, and mechanical properties of the aggregates. The regression analysis conducted on the different rocks separately showed that correlations coefficients obtained between the IS(50), SHR, UCS and mechanical properties of the aggregates were stronger than those of the grouped rocks. The T-test and F-test showed that the derived models were valid. This study has shown that the mechanical properties of the aggregates can be estimated from IS(50), SHR and USC but the influence of rock type on the relationships should be taken into consideration.

Second Korean guidelines for the management of ulcerative colitis

PubMed Central

Choi, Chang Hwan; Moon, Won; Kim, You Sun; Kim, Eun Soo; Lee, Bo-In; Jung, Yunho; Yoon, Yong Sik; Lee, Heeyoung; Park, Dong Il

2017-01-01

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the IBD study group of the Korean Association for the Study of Intestinal Diseases established the first Korean guidelines for the management of UC in 2012. This is an update of the first guidelines. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations. PMID:28239313

Effect of Tai Chi on physical function, fall rates and quality of life among older stroke survivors.

PubMed

Taylor-Piliae, Ruth E; Hoke, Tiffany M; Hepworth, Joseph T; Latt, L Daniel; Najafi, Bijan; Coull, Bruce M

2014-05-01

To examine the effect of a 12-week Tai Chi (TC) intervention on physical function and quality of life. Single-blind, randomized controlled trial. General community. Community-dwelling survivors of stroke (N=145; 47% women; mean age, 70y; time poststroke: 3y; ischemic stroke: 66%; hemiparesis: 73%) who were aged ≥50 years and were ≥3 months poststroke. Yang style 24-posture short-form TC (n=53), strength and range of movement exercises (SS) (n=44), or usual care (UC) (n=48) for 12 weeks. The TC and SS groups attended a 1-hour class 3 times per week, whereas the UC group had weekly phone calls. Physical function: Short Physical Performance Battery, fall rates, and 2-minute step test; quality of life: Medical Outcomes Study 36-Item Short-Form Health Survey, Center for Epidemiologic Studies Depression Scale, and Pittsburgh Sleep Quality Index. During the intervention, TC participants had two thirds fewer falls (5 falls) than the SS (14 falls) and UC (15 falls) groups (χ(2)=5.6, P=.06). There was a significant group by time interaction for the 2-minute step test (F2,142=4.69, P<.01). Post hoc tests indicated that the TC (t53=2.45, P=.02) and SS (t44=4.63, P<.01) groups had significantly better aerobic endurance over time, though not in the UC group (t48=1.58, P=.12). Intervention adherence rates were 85%. TC and SS led to improved aerobic endurance, and both are suitable community-based programs that may aid in stroke recovery and community reintegration. Our data suggest that a 12-week TC intervention was more effective in reducing fall rates than SS or UC interventions. Future studies examining the effectiveness of TC as a fall prevention strategy for community-dwelling survivors of stroke are recommended. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Determining the importance of model calibration for forecasting absolute/relative changes in streamflow from LULC and climate changes

USGS Publications Warehouse

Niraula, Rewati; Meixner, Thomas; Norman, Laura M.

2015-01-01

Land use/land cover (LULC) and climate changes are important drivers of change in streamflow. Assessing the impact of LULC and climate changes on streamflow is typically done with a calibrated and validated watershed model. However, there is a debate on the degree of calibration required. The objective of this study was to quantify the variation in estimated relative and absolute changes in streamflow associated with LULC and climate changes with different calibration approaches. The Soil and Water Assessment Tool (SWAT) was applied in an uncalibrated (UC), single outlet calibrated (OC), and spatially-calibrated (SC) mode to compare the relative and absolute changes in streamflow at 14 gaging stations within the Santa Cruz River Watershed in southern Arizona, USA. For this purpose, the effect of 3 LULC, 3 precipitation (P), and 3 temperature (T) scenarios were tested individually. For the validation period, Percent Bias (PBIAS) values were >100% with the UC model for all gages, the values were between 0% and 100% with the OC model and within 20% with the SC model. Changes in streamflow predicted with the UC and OC models were compared with those of the SC model. This approach implicitly assumes that the SC model is “ideal”. Results indicated that the magnitude of both absolute and relative changes in streamflow due to LULC predicted with the UC and OC results were different than those of the SC model. The magnitude of absolute changes predicted with the UC and SC models due to climate change (both P and T) were also significantly different, but were not different for OC and SC models. Results clearly indicated that relative changes due to climate change predicted with the UC and OC were not significantly different than that predicted with the SC models. This result suggests that it is important to calibrate the model spatially to analyze the effect of LULC change but not as important for analyzing the relative change in streamflow due to climate change. This study also indicated that model calibration in not necessary to determine the direction of change in streamflow due to LULC and climate change.

Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease

PubMed Central

Wettermark, Björn; Löfberg, Robert; Eriksson, Irene; Sundström, Johan; Lördal, Mikael

2016-01-01

Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. Methods: This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. Results: A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. Conclusions: This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients. PMID:26733406

Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease?

PubMed

Büning, Carsten; Geissler, Nora; Prager, Matthias; Sturm, Andreas; Baumgart, Daniel C; Büttner, Janine; Bühner, Sabine; Haas, Verena; Lochs, Herbert

2012-10-01

A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls. In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment. Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005). An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

[Catalase gene rs1001179 polymorphism and oxidative stress in patients with chronic hepatitis C and ulcerative colitis].

PubMed

Bulatova, I A; Tretyakova, Yu I; Shchekotov, V V; Shchekotova, A P; Ulitina, P V; Krivtsov, A V; Nenasheva, O Yu

2015-01-01

To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory. Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients. In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047). The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

Mediators of a smoking cessation intervention for persons living with HIV/AIDS

PubMed Central

Vidrine, Damon J.; Kypriotakis, George; Li, Liang; Arduino, Roberto C.; Fletcher, Faith E.; Tamí-Maury, Irene; Gritz, Ellen R.

2015-01-01

Background Cigarette smoking among persons living with HIV (PLWH) is a pressing public health concern, and efforts to evaluate cessation treatments are needed. The purpose of the present study was to assess potential mechanisms of a cell phone-delivered intervention for HIV-positive smokers. Methods Data from 350 PLWH enrolled in a randomized smoking cessation treatment trial were utilized. Participants were randomized to either usual care (UC) or a cell phone intervention (CPI) group. The independent variable of interest was treatment group membership, while the dependent variable of interest was smoking abstinence at a 3-month follow-up. The hypothesized treatment mechanisms were depression, anxiety, social support, quit motivation and self-efficacy change scores. Results Abstinence rates in the UC and CPI groups were 4.7% (8 of 172) and 15.7% (28 of 178), respectively. The CPI group (vs. UC) experienced a larger decline in depression between baseline and the 3-month follow-up, and a decline in anxiety. Self-efficacy increased for the CPI group and declined for the UC group. Quit motivation and social support change scores did not differ by treatment group. Only self-efficacy met the predefined criteria for mediation. The effect of the cell phone intervention on smoking abstinence through change in self-efficacy was statistically significant (p<.001) and accounted for 17% of the total effect of the intervention on abstinence. Conclusions The findings further emphasize the important mechanistic function of self-efficacy in promoting smoking cessation for PLWH. Additional efforts are required to disentangle the relationships between emotional, distress motivation, and efficacious smoking cessation treatment. PMID:25542824

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

PubMed Central

Huang, Yan-Feng; Qu, Chang; Xu, Lie-Qiang; Su, Zi-Ren; Zeng, Hui-Fang; Zheng, Lin; Yi, Tie-Gang; Li, Hui-Lin; Chen, Jian-Ping

2018-01-01

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. PMID:29538417

Cal-Bridge and CAMPARE: Engaging Underrepresented Students in Physics and Astronomy

NASA Astrophysics Data System (ADS)

Rudolph, Alexander L.; Cal-Bridge and CAMPARE Teams

2018-01-01

We describe two programs, Cal-Bridge and CAMPARE, with the common mission of increasing participation of groups traditionally underrepresented in astronomy, through summer research opportunities, in the case of CAMPARE, scholarships in the case of Cal-Bridge, and significant mentoring in both programs, creating a national impact on their numbers successfully pursuing a PhD in the field.In 8 years, the CAMPARE program has sent 112 students, >80% from underrepresented groups, to conduct summer research at one of 14 major research institutions throughout the country. Of the CAMPARE scholars who have graduated with a Bachelor’s degree, almost two-thirds (65%) have completed or are pursuing graduate education in physics, astronomy, or a related field, at institutions including UCLA, UC Riverside, UC Irvine, UC Santa Barbara, USC, Stanford, Univ. of Arizona, Univ. of Washington, Univ. of Rochester, Michigan State Univ., Georgia Tech, Georgia State Univ., Kent State, Indiana Univ., Univ. of Oregon, Syracuse Univ., Montana State Univ., and the Fisk-Vanderbilt Master’s-to-PhD program.Now entering its fourth year, the Cal-Bridge program is a CSU-UC Bridge program comprised of >140 physics and astronomy faculty from 9 University of California (UC), 15 California State University (CSU), and 30 California Community College (CCC) campuses throughout California. In the first four years, 34 Cal-Bridge Scholars have been selected, including 22 Hispanic, 3 African-American and 13 women students, 10 of whom are from URM groups. Thirty (30) of the 34 Cal-Bridge Scholars are first generation college students. In the last two years, 11 of 13 Cal-Bridge Scholars have begun PhD programs in physics or astronomy at top PhD programs nationally. Three (3) of these 11 scholars have won NSF Graduate Research Fellowships; one more received an Honorable Mention. The next cohort applies this fall.Cal-Bridge provides much deeper mentoring and professional development experiences over the last two years of undergraduate and first year of graduate school to students from this diverse network of higher education institutions. Cal-Bridge Scholars benefit from substantial financial support, intensive, joint mentoring by CSU and UC faculty, professional development workshops, and exposure to research opportunities at the participating UC campuses.

Cal-Bridge and CAMPARE: Engaging Underrepresented Students in Physics and Astronomy

NASA Astrophysics Data System (ADS)

Rudolph, Alexander L.; Smecker-Hane, Tammy A.; Cal-Bridge Team; CAMPARE Team

2018-06-01

We describe two programs, Cal-Bridge and CAMPARE, with the common mission of increasing participation of groups traditionally underrepresented in astronomy, through summer research opportunities, in the case of CAMPARE, scholarships in the case of Cal-Bridge, and significant mentoring in both programs, creating a national impact on their numbers successfully pursuing a PhD in the field. In 9 years, the CAMPARE program has sent 150 students, >80% from underrepresented groups, to conduct summer research at one of 14 major research institutions throughout the country. Of the CAMPARE scholars who have graduated with a Bachelor’s degree, almost two-thirds (65%) have completed or are pursuing graduate education in physics, astronomy, or a related field, at institutions including UCLA, UC Riverside, UC Irvine, UC Santa Barbara, USC, Stanford, Univ. of Arizona, Univ. of Washington, Univ. of Rochester, Michigan State Univ., Georgia Tech, Georgia State Univ., Kent State, Indiana Univ., Univ. of Oregon, Syracuse Univ., Montana State Univ., and the Fisk- Vanderbilt Master’s-to-PhD program. Now in its fourth year, the Cal-Bridge program is a CSU-UC Bridge program comprised of physics and astronomy faculty from 9 University of California (UC), 15 California State University (CSU), and more than 30 California Community College (CCC) campuses throughout California. In the first four years, 34 Cal-Bridge Scholars have been selected, including 22 Hispanic, 3 African-American and 13 women students, 10 of whom are from URM groups. Thirty (30) of the 34 Cal-Bridge Scholars are first generation college students. In the last three years, 17 of 21 Cal-Bridge Scholars have begun or been accepted PhD programs in physics or astronomy at top PhD programs nationally. Three (3) of these scholars have won NSF Graduate Research Fellowships; one more received an Honorable Mention. Once selected, Cal-Bridge Scholars benefit from substantial financial support, intensive, joint mentoring by CSU and UC faculty, professional development workshops, and exposure to research opportunities at the participating UC campuses. Funding for this program is provided by NSF-DUE SSTEM Grant #1356133.

Long term effects of an integrated care intervention on hospital utilization in patients with severe COPD: a single centre controlled study.

PubMed

Titova, Elena; Steinshamn, Sigurd; Indredavik, Bent; Henriksen, Anne Hildur

2015-02-03

Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality globally. In Trondheim in 2008 an integrated care model (COPD-Home) consisting of an education program, self-management plan, home visits and a call centre for patient support and communication was developed. The objective was to determine the efficacy of an intervention according to the COPD-Home model in reducing hospital utilization among patients with COPD stage III and IV (GOLD 2007) discharged after hospitalization for acute exacerbations of COPD (AECOPD). A single centre, prospective, open, controlled clinical study comparing COPD-Home integrated care (IC) with usual care (UC). Ninety-one versus 81 patients mean age 73.4 ± 9.3 years (57% women) were included in the IC group (ICG) and the UC group (UCG) respectively, and after 2 years 51 and 49 patients were available for control in the respective groups. During the year prior to study start there were 71 hospital admissions (HA) in the ICG and 84 in the UCG. There was a 12.6% reduction in HA in the ICG during the first year of follow-up and a 46.5% reduction during the second year (p = 0.01) compared to an 8.3% increase during the first year and no change during the second year in the ICG. During the year prior to study start, the number of hospital days (HD) was 468 in the ICG and 479 in the UCG. In the IC group, the number of HD was reduced by 48.3% during the first year (p = 0.01), and remained low during the second year of follow-up (p=0.02). In the UC group, the number of HD remained unchanged during the follow-up period. There was a trend towards a shorter survival time among patients in the ICG compared to the UCG, hazard ratio 1.33 [95% CI 0.77 to 2.33]. Intervention according to the COPD-Home model reduced hospital utilization in patients with COPD III and IV with a persisting effect throughout the 2 years of follow-up. However, there was a trend towards a shorter survival time in the intervention group.

Overexpression of GATA-3 in T cells accelerates dextran sulfate sodium-induced colitis.

PubMed

Okamura, Midori; Yoh, Keigyou; Ojima, Masami; Morito, Naoki; Takahashi, Satoru

2014-01-01

Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis includes genetic, environmental, and immunological factors, such as T helper cells and their secreted cytokines. T helper cells are classified as Th1, Th2, and Th17 cells. However, it is unclear which T helper cells are important in UC. Dextran sulfate sodium (DSS)-induced colitis is a commonly used model of UC. In this study, we induced DSS colitis in Th1 dominant (T-bet transgenic (Tg)) mice, Th2 dominant (GATA-3 Tg) mice, and Th17 dominant (RORγt Tg) mice to elucidate the roles of T helper cell in DSS colitis. The results showed that GATA-3 Tg mice developed the most severe DSS colitis compared with the other groups. GATA-3 Tg mice showed a significant decreased in weight from day 1 to day 7, and an increased high score for the disease activity index compared with the other groups. Furthermore, GATA-3 Tg mice developed many ulcers in the colon, and many neutrophils and macrophages were detected on day 4 after DSS treatment. Measurement of GATA-3-induced cytokines demonstrated that IL-13 was highly expressed in the colon from DSS-induced GATA-3 Tg mice. In conclusion, GATA-3 overexpression in T-cells and IL-13 might play important roles in the development of DSS colitis.

Parameter Sensitivity Study of the Unreacted-Core Shrinking Model: A Computer Activity for Chemical Reaction Engineering Courses

ERIC Educational Resources Information Center

Tudela, Ignacio; Bonete, Pedro; Fullana, Andres; Conesa, Juan Antonio

2011-01-01

The unreacted-core shrinking (UCS) model is employed to characterize fluid-particle reactions that are important in industry and research. An approach to understand the UCS model by numerical methods is presented, which helps the visualization of the influence of the variables that control the overall heterogeneous process. Use of this approach in…

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

PubMed

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-12-14

To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

PubMed Central

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-01-01

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. RESULTS We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. PMID:29290652

Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.

PubMed

Cui, Huantian; Cai, Yuzi; Wang, Li; Jia, Beitian; Li, Junchen; Zhao, Shuwu; Chu, Xiaoqian; Lin, Jin; Zhang, Xiaoyu; Bian, Yuhong; Zhuang, Pengwei

2018-01-01

Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode , and Berberis , has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium , and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.

Experimental impedance investigation of an ultracapacitor at different conditions for electric vehicle applications

NASA Astrophysics Data System (ADS)

Zhang, Lei; Hu, Xiaosong; Wang, Zhenpo; Sun, Fengchun; Dorrell, David G.

2015-08-01

Ultracapacitors (UCs) are being increasingly deployed as a short-term energy storage device in various energy systems including uninterruptable power supplies, electrified vehicles, renewable energy systems, and wireless communication. They exhibit excellent power density and energy efficiency. The dynamic behavior of a UC, however, strongly depends on its impedance characteristics. In this paper, the impedance characteristics of a commercial UC are experimentally investigated through the well-adopted Electrochemical Impedance Spectroscopy (EIS) technique. The implications of the UC operating conditions (i.e., temperature and state of charge (SOC)) to the impedance are systematically examined. The results show that the impedance is highly sensitive to the temperature and SOC; and the temperature effect is more significant. In particular, the coupling effect between the temperature and SOC is illustrated, as well as the high-efficiency SOC window, which is highlighted. To further verify the reliability of the EIS-based investigation and to probe the sensitivity of UC parameters to the operating conditions, a dynamic model is characterized by fitting the collected impedance data. The interdependence of UC parameters (i.e., capacitance and resistance elements) on the temperature and SOC is quantitatively revealed. The impedance-based model is demonstrated to be accurate in two driving-cycle tests.

A search for the optimal duration of treatment with 6-mercaptopurine for ulcerative colitis.

PubMed

Lobel, Efrat Z; Korelitz, Burton I; Xuereb, Mark A; Panagopoulos, Georgia

2004-03-01

6-mercaptopurine has proven to be effective in the treatment and maintenance of remission of ulcerative colitis (UC). The optimal duration of treatment with 6-MP is unknown. The intention of this study was to determine the best duration of treatment with 6-MP in terms of maintenance efficacy once remission has been achieved. We reviewed the records from the inflammatory bowel disease (IBD) center at Lenox Hill Hospital and one large IBD practice in New York City of 334 patients treated with 6-MP for UC. These patients were followed from 4 months to 28.7 yr. Sixty-one patients were treated with 6-MP for at least 6 months and had at least a 3-month disease-free interval off steroids while on the medication. These patients were divided into two groups: Group 1 continued 6-MP and group 2 discontinued the drug at various times for reasons other than relapse. Time to relapse was calculated for both groups. A Kaplan-Meier survival analysis was employed and differences between the two groups were analyzed using the log-rank test. The median time to relapse in group 2 was 24 wk and in group 1 was 58 wk (p < 0.05). There were no significant differences between the two groups in age, gender, extent of disease, use of concomitant 5-ASA products, dose of 6-MP during remission, duration of UC, and duration of treatment with 6-MP before remission was achieved. Discontinuation of treatment with 6-MP while UC is in remission leads to a higher relapse rate than maintenance on 6-MP. Therefore, we favor the indefinite treatment with 6-MP in most patients.

Nationwide prevalence and drug treatment practices of inflammatory bowel diseases in Hungary: A population-based study based on the National Health Insurance Fund database.

PubMed

Kurti, Zsuzsanna; Vegh, Zsuzsanna; Golovics, Petra A; Fadgyas-Freyler, Petra; Gecse, Krisztina B; Gonczi, Lorant; Gimesi-Orszagh, Judit; Lovasz, Barbara D; Lakatos, Peter L

2016-11-01

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization. Our aim was to estimate the national prevalence of inflammatory bowel disease (IBD), CD and UC and to describe current drug treatment practices in CD and UC. Patients and drug dispensing events were identified according to international classification codes for UC and CD in in-patient care, non-primary out-patient care and drug prescription databases (2011-2013) of the National Health Insurance Fund. A total of 55,039 individuals (men: 44.6%) with physician-diagnosed IBD were alive in Hungary in 2013, corresponding to a prevalence of 0.55% (95% CI, 0.55-0.56). The prevalence of CD 0.20% (95% CI, 0.19-0.20), and UC was 0.34% (95% CI, 0.33-0.34). The prevalence both in men and women was the highest in the 20-39 year-olds in CD. Current use of immunosuppressives and biological therapy was highest in the pediatric CD population (44% and 15%) followed by adult CD (33% and 9%), while their use was lowest in elderly patients. Interestingly, current use of 5-ASA (5-aminosalicylates) was high in both UC and CD irrespective of the age group. The Hungarian IBD prevalence based on nationwide database of the National Health Insurance Fund was high. We identified significant differences in the drug prescription practices according to age-groups. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

PubMed Central

2012-01-01

Background Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Methods Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). Conclusions A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC. PMID:22726388

Primary Care Provider Perceptions of the Effectiveness of Two Self-Management Support Programs for Vulnerable Patients with Diabetes

PubMed Central

Ratanawongsa, Neda; Bhandari, Vijay K; Handley, Margaret; Rundall, Thomas; Hammer, Hali; Schillinger, Dean

2012-01-01

Background Primary care providers (PCPs) in safety net settings face barriers to optimizing care for patients with diabetes. We conducted this study to assess PCPs' perspectives on the effectiveness of two language-concordant diabetes self-management support programs. Methods One year postintervention, we surveyed PCPs whose patients with diabetes participated in a three-arm multiclinic randomized controlled trial comparing usual care (UC), weekly automated telephone self-management (ATSM) support with nurse care management, and monthly group medical visits (GMVs). We compared PCP perspectives on patient activation to create and achieve goals, quality of care, and barriers to care using regression models accounting for within-PCP clustering. Results Of 113 eligible PCPs caring for 330 enrolled patients, 87 PCPs (77%) responded to surveys about 245 (74%) enrolled patients. Intervention patients were more likely to be perceived by PCPs as activated to create and achieve goals for chronic care when compared with UC patients (standardized effect size, ATSM vs UC, +0.41, p = 0.01; GMV vs UC, +0.31, p = 0.05). Primary care providers rated quality of care as higher for patients exposed to ATSM compared to UC (odds ratio 3.6, p < 0.01). Compared with GMV patients, ATSM patients were more likely to be perceived by PCPs as overcoming barriers related to limited English proficiency (82% ATSM vs 44% GMV, p = 0.01) and managing medications (80% ATSM vs 53% GMV, p = 0.01). Conclusions Primary care providers perceived that patients receiving ATSM support had overcome barriers, participated more actively, and received higher quality diabetes care. These views of clinician stakeholders lend additional evidence for the potential to upscale ATSM more broadly to support PCPs in their care of diverse, multilinguistic populations. PMID:22401329

Exposure-efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn's Disease.

PubMed

Rosario, Maria; French, Jonathan L; Dirks, Nathanael L; Sankoh, Serap; Parikh, Asit; Yang, Huyuan; Danese, Silvio; Colombel, Jean-Frédéric; Smyth, Michael; Sandborn, William J; Feagan, Brian G; Reinisch, Walter; Sands, Bruce E; Sans, Miguel; Fox, Irving

2017-08-01

A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [UC] or Crohn's disease [CD] has been reported. Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data. Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated. Exposure-efficacy relationships at Week 6 and potential baseline covariate effects were explored using logistic regression and individual predicted cumulative average concentration through Week 6 [Caverage] as exposure measure. Higher vedolizumab concentrations were associated with higher clinical remission rates; the exposure-efficacy relationship was steeper for UC than CD. Unadjusted analyses overestimated the relationship, more so for CD. From covariate-adjusted models, average probability of remission at Week 6 increased by approximately 15% for UC and 10% for CD between Caverage values of 35 and 84 µg/ml [5th and 95th percentiles, respectively]. On average, patients with higher albumin, lower faecal calprotectin [UC only], lower C-reactive protein [CD only], and no previous tumour necrosis factor-α [TNFα] antagonist use had a higher remission probability. Previous TNFα antagonist use had the greatest impact; remission probability was approximately 10% higher in treatment-naïve patients. Higher vedolizumab serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD. This relationship is affected by several factors, including previous TNFα antagonist use. Prospective studies are needed to assess vedolizumab dose individualisation and optimisation. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis.

PubMed

Xu, L; Lochhead, P; Ko, Y; Claggett, B; Leong, R W; Ananthakrishnan, A N

2017-11-01

Breastfeeding is a modifiable factor that may influence development of inflammatory bowel diseases. However, literature on this has been inconsistent and not accounted for heterogeneity in populations and exposure. To conduct a meta-analysis to examine the association between breastfeeding in infancy and risk of Crohn's disease (CD) and ulcerative colitis (UC). A systematic search of Medline/PubMed and Embase was performed for full text, English-language literature through November 2016. Studies were included if they described breastfeeding in infancy in patients with CD or UC, and healthy controls. Data were pooled using a random effects model for analysis. A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months. Breastfeeding in infancy protects against the development of CD and ulcerative colitis. © 2017 John Wiley & Sons Ltd.

[Mechanism of leukocytapheresis effect in the treatment of ulcerative colitis].

PubMed

Sawada, K; Ohnishi, K; Fukunaga, K; Chikano, S; Egashira, A; Satomi, M; Shimoyama, T

1999-12-01

To solve adverse effects of high dose steroid administration for patients with moderately severe and severe ulcerative colitis (UC), additional use of leukocytapheresis (LCAP) was tried to settle colonic inflammation. We evaluated immunological changes in the treatment of LCAP using leukocyte removal filter for UC patients. We then assessed the clinical effectiveness of LCAP compared with that of high dose of steroid therapy. LCAP removed monocytes, granulocytes, and lymphocytes presenting CD 11 b+, CD 11 c+, and HLADR+, selectively from the patients. Proinflammatory cytokine productions measured such as TNF alpha, IL-1 beta, and IL 8 reduced and IL 10 increased immediately after LCAP compared with before perfusion. Improved rate was about 70% for LCAP group and about 40% for high dose steroid group (Refer J Gastroenterol). Selective removal of granulocyte, monocytes, and activated lymphocytes inhibits proinflammatory cytokine production and increases immune modulating cytokine productions (Refer Therapeutic Apheresis). Then quick inhibition of several inflammatory deteriorated factors simultaneously controls the activity and clinical symptoms of UC with less severe adverse effects. It can be considered one option for treatment of UC.

Internal or External Stenting of the Ureterovesical Anastomosis in Renal Transplantation.

PubMed

Fockens, M Matthijs; Alberts, Victor P; Bemelman, Frederike J; Laguna Pes, M Pilar; Idu, Mirza M

2016-01-01

Stenting of the ureterovesical anastomosis reduces the incidence of urological complications (UCs) after renal transplantation, but there are multiple stenting techniques, and there is no consensus regarding which technique is preferred. The aim of this study was to compare an internal versus an external stenting technique on the incidence of UCs. This is a retrospective analysis of 419 deceased donor renal transplantations performed between January 2008 and December 2013. Until 2011, 183 patients received an external stent through the ureterovesical anastomosis placed by suprapubic bladder puncture (SP stent). From 2011, 236 recipients received an internal double-J (JJ) stent. The rate of UC was 3.8% in JJ stents, compared to 9.3% in SP stents (p = 0.021). No difference in surgical ureter revision rate was observed between the groups (2.1 vs. 5.5%; p = 0.068). Urinary tract infection (UTI) rate and graft function were comparable between both groups. Internal JJ stenting significantly decreased the incidence of UC compared to an external SP stent. There was no difference in surgical ureter revision rate, UTI or graft function. © 2015 S. Karger AG, Basel.

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.

PubMed

McConville, Christopher; Smith, James M; McCoy, Clare F; Srinivasan, Priya; Mitchell, James; Holder, Angela; Otten, Ron A; Butera, Salvatore; Doncel, Gustavo F; Friend, David R; Malcolm, R Karl

2015-02-01

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

Urinary calculi increase the risk for adverse pregnancy outcomes: a nationwide study.

PubMed

Chung, Shiu-Dong; Chen, Yi-Hua; Keller, Jospeh J; Lin, Ching-Chun; Lin, Herng-Ching

2013-01-01

Using two large-scale nationwide population-based data sets, this study aimed to assess the risk of adverse pregnancy outcomes between mothers with and without urinary calculi. Cross-sectional study. Taiwan. This study included 3694 women who had live singleton births and received a diagnosis of urinary calculi (UC) in the year prior to their delivery, as well as 18 470 matched women without UC, who were used as a comparison group. Conditional logistic regression analyses were performed. Low birthweight, preterm birth, small for gestational age, cesarean section, lower Apgar score and pre-eclampsia/eclampsia. Women with UC had a higher prevalence of low-birthweight neonates (7.4 vs. 6.0%, p = 0.003), preterm births (9.5 vs. 7.3%, p < 0.001) and cesarean sections (43.1 vs. 35.4%, p < 0.001) than women without UC. After adjusting for potential confounding factors, women with UC were more likely than women without UC to have low-birthweight neonates (odds ratio 1.21, 95% confidence interval 1.05-1.39), preterm birth (odds ratio 1.28, 95% confidence interval 1.13-1.43) and cesarean sections (odds ratio 1.37, 95% confidence interval 1.28-1.48). There were increased risks for having low-birthweight, preterm infants and for experiencing cesarean section among women with UC in comparison to women without UC. © 2012 The Authors © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

[Effect of moxa-burning heat stimulating Liangmen (ST 21) and Zusanli (ST 36) on proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer].

PubMed

Peng, Li; Wang, Yadong; Chang, Xiaorong; Wu, Huangan; Liu, Mi; Wang, Hong; Chen, Jiaolong; Wang Chao; Quan, Renfu; Yang, Zongbao

2016-06-01

To observe the effect of moxa-burning heat stimulating acupoints of Liangmen (ST 21) and Zusanli (ST 36) on the proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer. Forty rats were randomly divided into four groups: negative control (NC), ulcer control (UC), acupoints of stomach meridian (ASM), and acupoints control (AC). The acute gastric ulcer model was established by bound and water immersion. Rats in NC and UC groups didn't receive any moxa-burning heat stimulating treatment, while rats in ASM and AC groups were treated with buringmoxa heat stimulating the acupoints of Liangmen (ST 21) and Zusanli (ST 36) and their controlled points, respectively. Rats in all groups were sacrificed after 12 consecutive days treatment. The ulcer index was evaluated by using Guth's method. The expression of tumor necrosis factor-alpha (TNF-α), apoptotic protease activating facter-1 (Apaf-1), Caspase-3, p21 activated kinase 1 (PAK1), extracellular regulated protein kinases 2 (ERK2), phosphorylated ERK2 (pERK2), phosphoinositide 3-kinase (PI3K) and RAC-alpha serine/threonine-protein kinase (Akt) in gastric mucosa was detected by enzyme linked immunosorbent assay (ELISA). Compared with UC group, the ulcer index of ASM and AC groups decreased, and the injured gastric mucosa was improved, the expression of TNF-α, Apaf-1 and Caspase-3 in gastric mucosa was significantly reduced (P < 0.05), while the expression of PAK1, ERK2, pERK2, PI3K and Akt in gastric mucosa was significantly increased (P < 0.05). And ASM showed better effect than AC group (P < 0.05). Moxa-burning Heat stimulating of Liangmen (ST 21) and Zusanli (ST 36) could promote the recovery of gastric mucosal lesion probably by inhibiting cell apoptosis and promoting cell proliferation in stress-induced gastric ulcer.

Protective Effect of Daikenchuto on Dextran Sulfate Sodium-Induced Colitis in Mice

PubMed Central

Matsunaga, Takaharu; Yamamoto, Naoki; Kawasato, Ryo; Shirasawa, Tomohiro; Goto, Atsushi; Fujisawa, Koichi; Takami, Taro; Okamoto, Takeshi; Nishikawa, Jun; Sakaida, Isao

2017-01-01

Aim. To investigate the effect of daikenchuto (TJ-100; DKT) for ulcerative colitis (UC) model mouse and assess its anti-inflammatory mechanisms. Methods. We evaluated the effects of DKT on dextran sulfate sodium- (DSS-) induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL-) 10, IL-1β, and tumor necrosis factor-α mRNA expression profiles were analyzed using real-time PCR. Second, we assessed the long-term effects of DKT, by comparing survival time between 2% DSS and 2% DSS with DKT groups. Results. After 7 days, the colon lengths of DSS + DKT group were longer than those of the DSS group (mean values: 6.11 versus 5.69 cm, p < 0.05). Furthermore, compared to DSS group, the DSS + DKT group maintained significantly higher levels of serum hemoglobin (13.1 versus 10.7 g/dL, p < 0.05) and exhibited significantly higher expression levels of IL-10 (p < 0.05). The 2% DSS + DKT group exhibited significantly longer survival time than the 2% DSS group (70 versus 44 days, p < 0.01). Conclusion. Our results indicate that DKT prevented inflammation in the colon, indicating its potential as a new therapeutic agent for UC. PMID:28210268

Protective Effect of Daikenchuto on Dextran Sulfate Sodium-Induced Colitis in Mice.

PubMed

Matsunaga, Takaharu; Hashimoto, Shinichi; Yamamoto, Naoki; Kawasato, Ryo; Shirasawa, Tomohiro; Goto, Atsushi; Fujisawa, Koichi; Takami, Taro; Okamoto, Takeshi; Nishikawa, Jun; Sakaida, Isao

2017-01-01

Aim . To investigate the effect of daikenchuto (TJ-100; DKT) for ulcerative colitis (UC) model mouse and assess its anti-inflammatory mechanisms. Methods . We evaluated the effects of DKT on dextran sulfate sodium- (DSS-) induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL-) 10, IL-1 β , and tumor necrosis factor- α mRNA expression profiles were analyzed using real-time PCR. Second, we assessed the long-term effects of DKT, by comparing survival time between 2% DSS and 2% DSS with DKT groups. Results . After 7 days, the colon lengths of DSS + DKT group were longer than those of the DSS group (mean values: 6.11 versus 5.69 cm, p < 0.05). Furthermore, compared to DSS group, the DSS + DKT group maintained significantly higher levels of serum hemoglobin (13.1 versus 10.7 g/dL, p < 0.05) and exhibited significantly higher expression levels of IL-10 ( p < 0.05). The 2% DSS + DKT group exhibited significantly longer survival time than the 2% DSS group (70 versus 44 days, p < 0.01). Conclusion . Our results indicate that DKT prevented inflammation in the colon, indicating its potential as a new therapeutic agent for UC.

Apixaban pharmacodynamic activity in umbilical cord, paediatric, and adult plasma.

PubMed

Yetman, Robert J; Barrett, Yu Chen; Wang, Zhaoqing; Adamczyk, Robert; Wang, Jessie; Ramacciotti, Eduardo; Frost, Charles

2017-07-26

The objective was to characterise apixaban pharmacodynamic (PD) activity in umbilical cord (UC), paediatric, and adult plasma. Plasma was obtained from blood samples from six UC donors, 70 paediatric (neonates [birth-≤1 month], infants [>1-≤6 months], toddlers [>6 months-≤2 years], young children [>2-≤6 years], children [>6-≤12 years], adolescents [>12-≤18 years]), and six adult (19-45 years) subjects. Plasma spiked with apixaban 0 (baseline), 30, or 110 ng/ml was analysed for anti-factor Xa activity, factor X levels, prothrombin time (PT), and modified PT (mPT). Apixaban had similar concentration-related effects on anti-factor Xa activity across groups (30 ng/ml: 0.223-0.295 IU/ml; 110 ng/ml: 1.212-1.474 IU/ml). Endogenous baseline factor X levels were 43 %-68 % lower in plasma from UC and subjects ≤6 months versus adults. Factor Xa inhibition (percentage change from baseline in apparent factor X levels) was similar for both apixaban concentrations across groups, except UC, neonate, and infant groups, which showed greater inhibition vs adults for apixaban 110 ng/ml. Baseline PT and mPT were similar across groups. Apixaban had no effect on PT at the concentrations tested. Apixaban 110 ng/ml prolonged mPT similarly across groups (44.4-53.2 s to 64.5-70.0 s); no prolongation was found with apixaban 30 ng/ml. Apixaban demonstrated consistent concentration-related effects on other PD endpoints in plasma samples from all age groups, except factor Xa inhibition.

Combined Diosmectite and Mesalazine Treatment for Mild-to-Moderate Ulcerative Colitis: A Randomized, Placebo-Controlled Study

PubMed Central

Jiang, Xue-Liang; Wang, Hua-Hong; Cui, Hui-Fei

2015-01-01

Background The relapse rate of ulcerative colitis (UC) is high. The efficacy of combined diosmectite and mesalazine treatment for active mild-to-moderate UC was investigated. Material/Methods A total of 120 patients with UC were enrolled in this randomized, single-blind, placebo-controlled study. Sixty patients were assigned to the Diosmectite group (diosmectite and mesalazine) and 60 were assigned to Placebo group (placebo and mesalazine). In the induction phase, the primary end point was the clinical remission rate at 8 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, C-reactive protein levels, and defecation frequency. In the maintenance phase, the primary end point was clinical remission at 52 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, and defecation frequency. Results At 8 weeks, the Diosmectite group had a significantly higher clinical remission rate (68.3% vs. 50%) and mucosal healing rate (66.7% vs. 48.3%) compared with the Placebo group. There were no significant differences in clinical response rates, Mayo score, erythrocyte sedimentation rate, C-reactive protein, or defecation frequency. At 52 weeks, the Diosmectite group had a significantly higher clinical remission rate (61.7% vs. 40%) and mucosal healing rate (60% vs. 38.3%) compared with the Placebo group. Defecation frequency was lower, but this was not significant. Conclusions Combined diosmectite and mesalazine treatment successfully induced and maintained the treatment of active mild-to-moderate UC as indicated by higher rates of clinical remission and mucosal healing. PMID:25582578

University-Community Partnership Models: Employing Organizational Management Theories of Paradox and Strategic Contradiction

ERIC Educational Resources Information Center

Bowers, Amanda M.

2017-01-01

University-Community (U-C) partnerships have the potential to respond to society's most pressing needs through engaged scholarship. Despite this promise, partnerships face paradoxical tensions and inherent contradictions that are often not fully addressed in U-C partnership models or frameworks, or in practice. This article seeks to explore the…

Florid urticarial vasculitis heralding a flare up of ulcerative colitis.

PubMed

Boules, Evon; Lyon, Calum

2014-12-22

A 75-year-old man with ulcerative colitis (UC) and diet controlled diabetes mellitus presented with a 3-week history of slightly itchy, red plaques on both lower limbs ascending gradually to cover the trunk and arms. One week later, he developed a flare up of his UC. Routine blood tests showed modest drop in haemoglobin (122 g/L) and C reactive protein (85 mg/L). Serology was remarkable for high antiproteinase 3 (c-ANCA). Serum electrophoresis showed a mildly positive paraprotein band (γ region). Stool culture was negative. Urine analysis showed proteinuria. Skin biopsy showed features of urticarial vasculitis (UV). He underwent a flexible sigmoidoscopy after the flare up showed mildly active UC. The patient was given hydrocortisone for 7 days and then prednisolone. Both rash and UC subsided. Electrophoresis was repeated 4 weeks later showing normal pattern. Prednisolone has been gradually reduced. Although rare, UV can be considered as one of the skin manifestations of UC. 2014 BMJ Publishing Group Ltd.

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

In situ synthesis and characterization of uranium carbide using high temperature neutron diffraction

NASA Astrophysics Data System (ADS)

Reiche, H. Matthias; Vogel, Sven C.; Tang, Ming

2016-04-01

We investigated the formation of UCx from UO2+x and graphite in situ using neutron diffraction at high temperatures with particular focus on resolving the conflicting reports on the crystal structure of non-quenchable cubic UC2. The agents were UO2 nanopowder, which closely imitates nano grains observed in spent reactor fuels, and graphite powder. In situ neutron diffraction revealed the onset of the UO2 + 2C → UC + CO2 reaction at 1440 °C, with its completion at 1500 °C. Upon further heating, carbon diffuses into the uranium carbide forming C2 groups at the octahedral sites. This resulting high temperature cubic UC2 phase is similar to the NaCl-type structure as proposed by Bowman et al. Our novel experimental data provide insights into the mechanism and kinetics of formation of UC as well as characteristics of the high temperature cubic UC2 phase which agree with proposed rotational rehybridization found from simulations by Wen et al.

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson's Disease: A Pilot Randomized Controlled Trial.

PubMed

Vergara-Diaz, Gloria; Osypiuk, Kamila; Hausdorff, Jeffrey M; Bonato, Paolo; Gow, Brian J; Miranda, Jose Gv; Sudarsky, Lewis R; Tarsy, Daniel; Fox, Michael D; Gardiner, Paula; Thomas, Cathi A; Macklin, Eric A; Wayne, Peter M

2018-01-01

To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson's disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Two-arm, wait-list controlled RCT. Tertiary care hospital. Thirty-two subjects aged 40-75 diagnosed with idiopathic PD within 10 years. Six-month TC intervention added to usual care (UC) versus UC alone. Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson's Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [-0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

Telephone and In-Person Cognitive Behavioral Therapy for Major Depression after Traumatic Brain Injury: A Randomized Controlled Trial

PubMed Central

Bombardier, Charles H.; Vannoy, Steven; Dyer, Joshua; Ludman, Evette; Dikmen, Sureyya; Marshall, Kenneth; Barber, Jason; Temkin, Nancy

2015-01-01

Abstract Major depressive disorder (MDD) is prevalent after traumatic brain injury (TBI); however, there is a lack of evidence regarding effective treatment approaches. We conducted a choice-stratified randomized controlled trial in 100 adults with MDD within 10 years of complicated mild to severe TBI to test the effectiveness of brief cognitive behavioral therapy administered over the telephone (CBT-T) (n=40) or in-person (CBT-IP) (n=18), compared with usual care (UC) (n=42). Participants were recruited from clinical and community settings throughout the United States. The main outcomes were change in depression severity on the clinician-rated 17 item Hamilton Depression Rating Scale (HAMD-17) and the patient-reported Symptom Checklist-20 (SCL-20) over 16 weeks. There was no significant difference between the combined CBT and UC groups over 16 weeks on the HAMD-17 (treatment effect=1.2, 95% CI: −1.5–4.0; p=0.37) and a nonsignificant trend favoring CBT on the SCL-20 (treatment effect=0.28, 95% CI: −0.03–0.59; p=0.074). In follow-up comparisons, the CBT-T group had significantly more improvement on the SCL-20 than the UC group (treatment effect=0.36, 95% CI: 0.01–0.70; p=0.043) and completers of eight or more CBT sessions had significantly improved SCL-20 scores compared with the UC group (treatment effect=0.43, 95% CI: 0.10–0.76; p=0.011). CBT participants reported significantly more symptom improvement (p=0.010) and greater satisfaction with depression care (p<0.001), than did the UC group. In-person and telephone-administered CBT are acceptable and feasible in persons with TBI. Although further research is warranted, telephone CBT holds particular promise for enhancing access and adherence to effective depression treatment. PMID:25072405

Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy.

PubMed

Palagiano, A; Bulletti, C; Pace, M C; DE Ziegler, D; Cicinelli, E; Izzo, A

2004-12-01

Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospective, randomized, double-blind study in one medical center carried out with a parallel trial. The primary objective was to establish the effects of vaginal progesterone (Crinone 8%) in reducing both pain and uterine contractions (UCs). The gel with or without (placebo) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The secondary objective of the study was to evaluate the outcome of the pregnancies. The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration (P < 0.005). The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried (P < 0.05). In conclusion, patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain. The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase.

Efficacy of cell phone-delivered smoking cessation counseling for persons living with HIV/AIDS: 3-month outcomes.

PubMed

Vidrine, Damon J; Marks, Rachel M; Arduino, Roberto C; Gritz, Ellen R

2012-01-01

Substantial evidence indicates that cigarette smoking among people living with HIV/AIDS (PLWHA) represents a significant public health concern. However, few efforts to assess smoking cessation interventions targeting this population have been reported. In this brief report, 3-month outcomes from an ongoing treatment trial for PLWHA who smoke are described. Study participants were recruited from a large HIV care center serving a diverse population of PLWHA. A two-group randomized design was used to compare the efficacy of usual-care (UC) smoking cessation treatment versus a cell phone intervention (CPI). Follow-ups were conducted at the HIV clinic 3 months postenrollment. Using an intent-to-treat approach, a series of multiple regression models were used to compare smoking outcomes in the 2 groups. Four hundred and seventy-four participants were enrolled and randomized, UC (n = 238) and CPI (n = 236). Mean age in the sample was 44.8 (SD = 8.1) years, and the majority were male (70.0%), Black (76.6%), and had an education level of high school or less (77.5%). At follow-up, participants in the CPI group were 4.3 (95% CI = 1.9, 9.8) times more likely to be abstinent (7 day) compared with those in the UC group. Similarly, significant point estimates were observed for the other smoking outcomes of interest. Findings from this preliminary report indicate that a smoking cessation intervention for PLWHA consisting of cell phone-delivered proactive counseling results in significantly higher abstinence rates compared with a standard care approach. Evaluation of the long-term (6-month and 12-month) efficacy of the CPI approach is ongoing.

Efficacy of Cell Phone–Delivered Smoking Cessation Counseling for Persons Living With HIV/AIDS: 3-Month Outcomes

PubMed Central

Marks, Rachel M.; Arduino, Roberto C.; Gritz, Ellen R.

2012-01-01

Introduction: Substantial evidence indicates that cigarette smoking among people living with HIV/AIDS (PLWHA) represents a significant public health concern. However, few efforts to assess smoking cessation interventions targeting this population have been reported. In this brief report, 3-month outcomes from an ongoing treatment trial for PLWHA who smoke are described. Methods: Study participants were recruited from a large HIV care center serving a diverse population of PLWHA. A two-group randomized design was used to compare the efficacy of usual-care (UC) smoking cessation treatment versus a cell phone intervention (CPI). Follow-ups were conducted at the HIV clinic 3 months postenrollment. Using an intent-to-treat approach, a series of multiple regression models were used to compare smoking outcomes in the 2 groups. Results: Four hundred and seventy-four participants were enrolled and randomized, UC (n = 238) and CPI (n = 236). Mean age in the sample was 44.8 (SD = 8.1) years, and the majority were male (70.0%), Black (76.6%), and had an education level of high school or less (77.5%). At follow-up, participants in the CPI group were 4.3 (95% CI = 1.9, 9.8) times more likely to be abstinent (7 day) compared with those in the UC group. Similarly, significant point estimates were observed for the other smoking outcomes of interest. Conclusions: Findings from this preliminary report indicate that a smoking cessation intervention for PLWHA consisting of cell phone–delivered proactive counseling results in significantly higher abstinence rates compared with a standard care approach. Evaluation of the long-term (6-month and 12-month) efficacy of the CPI approach is ongoing. PMID:21669958

Ultrasonographic assessment of the thyroid gland structure in inflammatory bowel disease patients.

PubMed

Neubauer, Katarzyna; Woźniak-Stolarska, Barbara

2012-01-01

The etiopathogenesis of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is still not fully elucidated and seems to be multifactorial. It has been suggested that genetic, immunological and environmental factors participate in IBD development. IBD extraintestinal manifestations include rheumatic, metabolic, dermatologic, ophthalmologic, hepatobiliary, pancreatic, urologic, pulmonary, neurological, hematological and thromboembolic complications. Thyroid gland diseases have not been confirmed as extraintestinal manifestations of IBD. However, it is known that some thyroid diseases share an immunological background with IBD, and that dysfunction of the thyroid gland may induce gastrointestinal symptoms. Ultrasound examination is the gold standard for evaluation of thyroid gland morphology. This study was designed to assess the prevalence of abnormalities in the structure of the thyroid gland in IBD patients and to compare it to the control group. The study group consisted of 199 consecutive IBD patients (80 CD patients and 119 UC patients) hospitalized at the Department of Gastroenterology and Hepatology of Wroclaw Medical University (Poland). The control group consisted of 42 healthy volunteers and patients with functional gastrointestinal disorders. The most common finding in the ultrasound examination in IBD patients were tumors. Tumors, which were smaller than or equal to 10 mm were present in 11.5% of IBD patients; and tumors larger than 10 mm were present in 13.1%. These results show that small tumors (less than 10 mm in diameter) of the thyroid gland are more frequent among patients with CD and UC compared to the control group (p = 0.0001 and p = 0.001, respectively). Additionally, enlargement of the thyroid gland occurs more often in UC patients compared to the control group (p = 0.003). There was no difference in the frequency of thyroid abnormalities between UC and CD patients. In patients with inflammatory bowel diseases focal lesions relating to tumors of the thyroid gland are more common than in the control group. In patients with ulcerative colitis enlargement of the thyroid gland is more frequent than in the control group. Initial assessments of IBD patients should include ultrasound examinations of the thyroid gland.

MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1.

PubMed

Lv, Bo; Liu, Zhihui; Wang, Shuping; Liu, Fengbin; Yang, Xiaojun; Hou, Jiangtao; Hou, Zhengkun; Chen, Bin

2014-01-01

While it's widely accepted that the etiology of ulcerative colitis (UC) involves both genetic and environmental factors, the pathogenesis of ulcerative colitis is still poorly understood. Intestinal epithelial apoptosis is one of the most common histopathological changes of UC and the expression of a number of apoptosis genes may contribute to the progression of UC. MicroRNAs have recently emerged as powerful regulators of diverse cellular processes and have been shown to be involved in many immune-mediated disorders such as psoriasis, rheumatoid arthritis, lupus, and asthma. A unique microRNA expression profile has been identified in UC, suggesting that, microRNAs play an important role in the pathogenesis of UC. We investigated the role of miR-29a in intestinal epithelial apoptosis in UC. The expression of miR-29a and Mcl-1, an anti-apoptotic BCL-2 family member, was evaluated in both UC patients and UC mice model induced by dextran sodium sulfate (DSS). The apoptosis rate of intestinal epithelial cells was also evaluated. In UC patients and DSS-induced UC in mice, the expression of miR-29a and Mcl-1, were up-regulated and down-regulated, respectively. We identified a miR-29a binding site (7 nucleotides) on the 3'UTR of mcl-1 and mutation in this binding site on the 3'UTR of mcl-1 led to mis-match between miR-29a and mcl-1. Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1. miR-29a is involved in the pathogenesis of UC by regulating intestinal epithelial apoptosis via Mcl-1.

Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis

PubMed Central

da Silva, Bruno César; Lyra, Andre Castro; Rocha, Raquel; Santana, Genoile Oliveira

2014-01-01

Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of the colon and rectum. The hallmark clinical symptom of UC is bloody diarrhea. The clinical course is marked by exacerbations and remissions, which may occur spontaneously or in response to treatment changes or intercurrent illnesses. UC is most commonly diagnosed in late adolescence or early adulthood, but it can occur at any age. The incidence of UC has increased worldwide over recent decades, especially in developing nations. In contrast, during this period, therapeutic advances have improved the life expectancy of patients, and there has been a decrease in the mortality rate over time. It is important to emphasize that there is considerable variability in the phenotypic presentation of UC. Within this context, certain clinical and demographic characteristics are useful in identifying patients who tend to have more severe evolution of the disease and a poor prognosis. In this group of patients, better clinical surveillance and more intensive therapy may change the natural course of the disease. The aim of this article was to review the epidemiology and demographic characteristics of UC and the factors that may be associated with its clinical prognosis. PMID:25071340

Supra-pubic versus urethral catheter after robot-assisted radical prostatectomy: systematic review of current evidence.

PubMed

Bertolo, Riccardo; Tracey, Andrew; Dasgupta, Prokar; Rocco, Bernardo; Micali, Salvatore; Bianchi, Giampaolo; Hampton, Lance; Tewari, Ash K; Porpiglia, Francesco; Autorino, Riccardo

2018-03-29

To provide latest evidence on the use of suprapubic catheter (SPC) versus urethral catheter (UC) after robot-assisted laparoscopic radical prostatectomy (RARP). A systematic revision of literature was performed up to September 2017 using different search engines (Pubmed, Ovid, Scopus) to identified studies comparing the use of SPC versus standard UC after RARP. Identification and selection of the studies were conducted according to the preferred reporting items for systematic reviews and meta-analysis criteria. For continuous outcomes, the weighted mean difference (WMD) was used as a summary measure, whereas the odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI) was calculated for binary variables. RR was preferred in cases of a high number of events to avoid overestimation. Pooled estimates were calculated using the random-effect model to account for clinical heterogeneity. All statistical analyses were performed using Review manager 5 (Cochrane Collaboration, Oxford, UK). Eight studies were identified and included in this systematic review, namely 3 RCTs, 4 non-randomized prospective studies, and one retrospective study. A total of 966 RARP cases were collected for the cumulative analysis. Among them, 492 patients received standard UC and 474 SPC placement after RARP. UC patients had higher baseline PSA (WMD 0.44 ng/ml; p = 0.02). Visual Analog Scale (VAS) score was found to be significantly lower in patients with SPC at postoperative day 7 (WMD 0.53; 95% CI 0.13-0.93; p = 0.009). Regarding penile pain, a significant difference in favor of the SPC group was found at postoperative day 7 assessment (WMD 1.2; 95% CI 0.82-1.6; p < 0.001). More patients in the SPC group reported "not at all" or "minimal pain" at this time point (OR 0.17, 95% CI 0.06, 0.44; p < 0.001). No significant differences were found in terms of continence recovery rate at 6-12 weeks between the groups (UC 78.7%, 88.2%; RR 0.92, 95% CI 0.84, 1.01; p = 0.09). Similarly, no differences were found in terms of catheter-related issues (p = 0.17). However, UC patients had lower likelihood of overall complications (OR 0.44, 95% CI 0.21-0.89, p = 0.02). Available evidence suggests that the use of SPC can be a viable option for postoperative urine drainage after RARP, as it can translate into decreased postoperative pain without carrying a significant higher risk of catheter-related complications. Further investigation seems to be warranted, ideally within the framework of a multicentre randomized study with standardized analysis of outcomes.

17-β Estradiol reduces atherosclerosis without exacerbating lupus in ovariectomized systemic lupus erythematosus-susceptible LDLr(-/-) mice.

PubMed

Shelton, K A; Cline, J M; Cann, J A

2013-04-01

To test the hypothesis that estrogen treatment in a radiation chimera mouse model of systemic lupus erythematosus (SLE) and atherosclerosis will increase SLE-associated atherosclerosis by increasing autoantibody production and inflammation. We used a radiation chimera mouse model in which bone marrow from the polygenic B6.Sle1.2.3 model of SLE was transferred to the low density lipoprotein receptor knock out (LDLr(-/-)) model of atherosclerosis on a C57BL/6 background (Sle/LDLr(-/-)). Ovariectomized chimeric mice were treated for 10 weeks with either 5.6 μg/day of 17β-estradiol or placebo; outcomes included atherosclerosis plaque size, anti-dsDNA autoantibody production and renal pathology. Mean atherosclerosis plaque size was 67.4 ± 7.6% smaller in the estrogen treated group (p < 0.0001). Estrogen treated Sle/LDLr(-/-) mice had no significant difference in serum cholesterol concentration, lipoprotein distribution, anti-dsDNA autoantibody concentration, antibody isotype concentration and renal histopathology score compared to placebo. However, they had significantly lower mean urine protein to urine creatinine ratio (UP:UC). There was no correlation between atherosclerosis lesion size and either the renal histology score or UP:UC ratio in Sle/LDLr(-/-) mice. These results indicate that 17β-estradiol is atheroprotective within the context of murine SLE independent of changes in serum cholesterol concentration, autoantibody concentration, or renal pathology. The SLE phenotype in Sle/LDLr(-/-) mice is not exacerbated by exogenous 17β-estradiol administration, and the reduced UP:UC ratio suggests a protective effect against lupus nephritis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

17-β Estradiol reduces atherosclerosis without exacerbating lupus in ovariectomized systemic lupus erythematosus-susceptible LDLr−/− mice

PubMed Central

Shelton, KA; Cline, JM; Cann, JA

2013-01-01

Objective To test the hypothesis that estrogen treatment in a radiation chimera mouse model of systemic lupus erythematosus (SLE) and atherosclerosis will increase SLE-associated atherosclerosis by increasing autoantibody production and inflammation. Methods We used a radiation chimera mouse model in which bone marrow from the polygenic B6.Sle1.2.3 model of SLE was transferred to the low density lipoprotein receptor knock out (LDLr−/−) model of atherosclerosis on a C57BL/6 background (Sle/LDLr−/−). Ovariectomized chimeric mice were treated for 10 weeks with either 5.6 ug/day of 17β-estradiol or placebo; outcomes included atherosclerosis plaque size, anti-dsDNA autoantibody production and renal pathology. Results Mean atherosclerosis plaque size was 67.4 ± 7.6% smaller in the estrogen treated group (p<0.0001). Estrogen treated Sle/LDLr−/− mice had no significant difference in serum cholesterol concentration, lipoprotein distribution, anti-dsDNA autoantibody concentration, antibody isotype concentration and renal histopathology score compared to placebo. However, they had significantly lower mean urine protein to urine creatinine ratio (UP:UC). There was no correlation between atherosclerosis lesion size and either the renal histology score or UP:UC ratio in Sle/LDLr−/− mice. Conclusion These results indicate that 17β-estradiol is atheroprotective within the context of murine SLE independent of changes in serum cholesterol concentration, autoantibody concentration, or renal pathology. The SLE phenotype in Sle/LDLr−/− mice is not exacerbated by exogenous 17β-estradiol administration, and the reduced UP:UC ratio suggests a protective effect against lupus nephritis. PMID:23395521

[Hormonal changes during relaxation].

PubMed

Gallois, P; Forzy, G; Dhont, J L

1984-01-01

Among 10 subjects who practiced autogenic training (AT) and 10 subjects who practiced transcendental meditation (TM), compared to 10 control subjects during 40 minutes, have been observed the following results: --decrease in cortisol plasma level (reaching a minima of 2 g/100 ml), --decrease in prolactin plasma level, --the basal plasma level of cortisol and prolactin were significantly lower in the TM group. Lastly, the urinary catecholamines (UC) increase after 40 minutes of rest in the control group, whereas the UC decrease in the TA group and most certainly in the TM group. All these variations indicate a humoral modification which seems to be the opposite of the state induced by stress.

Maternal Pre-Gravid Obesity Changes Gene Expression Profiles Towards Greater Inflammation and Reduced Insulin Sensitivity in Umbilical Cord

PubMed Central

Thakali, Keshari M.; Saben, Jessica; Faske, Jennifer B.; Lindsey, Forrest; Gomez-Acevedo, Horacio; Lowery, Curtis L.; Badger, Thomas M.; Andres, Aline; Shankar, Kartik

2014-01-01

Background Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). Methods UCs from 12 lean (pre-gravid BMI < 24.9) and 10 overweight/obese (OW/OB, pre-gravid BMI ≥25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays (Affymetrix). Metabolic parameters were assayed in mother’s plasma and cord blood. Results Although offspring birth weight and adiposity (at 2-wk) did not differ between groups, expression of 232 transcripts was affected in UC from OW/OB compared to those of lean mothers. GSEA analysis revealed an up-regulation of genes related to metabolism, stimulus and defense response and inhibitory to insulin signaling in the OW/OB group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from OW/OB moms, while endothelin receptor B, KFL10, PEG3 and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST and SOCS1 were positively correlated (p<0.05) with mother’s first trimester body fat mass (%). Conclusions Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. PMID:24819376

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial.

PubMed

Mijwel, Sara; Backman, Malin; Bolam, Kate A; Jervaeus, Anna; Sundberg, Carl Johan; Margolin, Sara; Browall, Maria; Rundqvist, Helene; Wengström, Yvonne

2018-02-01

Exercise training is an effective and safe way to counteract cancer-related fatigue (CRF) and to improve health-related quality of life (HRQoL). High-intensity interval training has proven beneficial for the health of clinical populations. The aim of this randomized controlled trial was to compare the effects of resistance and high-intensity interval training (RT-HIIT), and moderate-intensity aerobic and high-intensity interval training (AT-HIIT) to usual care (UC) in women with breast cancer undergoing chemotherapy. The primary endpoint was CRF and the secondary endpoints were HRQoL and cancer treatment-related symptoms. Two hundred and forty women planned to undergo chemotherapy were randomized to supervised RT-HIIT, AT-HIIT, or UC. Measurements were performed at baseline and at 16 weeks. Questionnaires included Piper Fatigue Scale, EORTC-QLQ-C30, and Memorial Symptom Assessment Scale. The RT-HIIT group was superior to UC for CRF: total CRF (p = 0.02), behavior/daily life (p = 0.01), and sensory/physical (p = 0.03) CRF. Role functioning significantly improved while cognitive functioning was unchanged for RT-HIIT compared to declines shown in the UC group (p = 0.04). AT-HIIT significantly improved emotional functioning versus UC (p = 0.01) and was superior to UC for pain symptoms (p = 0.03). RT-HIIT reported a reduced symptom burden, while AT-HIIT remained stable compared to deteriorations shown by UC (p < 0.01). Only RT-HIIT was superior to UC for total symptoms (p < 0.01). 16 weeks of resistance and HIIT was effective in preventing increases in CRF and in reducing symptom burden for patients during chemotherapy for breast cancer. These findings add to a growing body of evidence supporting the inclusion of structured exercise prescriptions, including HIIT, as a vital component of cancer rehabilitation. Clinicaltrials.gov Registration Number: NCT02522260.

Different intraoperative kinematics with comparable clinical outcomes of ultracongruent and posterior stabilized mobile-bearing total knee arthroplasty.

PubMed

Kim, Tae Woo; Lee, Sang Min; Seong, Sang Cheol; Lee, Sahnghoon; Jang, Jak; Lee, Myung Chul

2016-09-01

There remains no consensus as to whether mobile total knee arthroplasty (TKA) should use a posterior cruciate ligament-sacrificing ultracongruent (UC) or a posterior cruciate ligament-substituting posterior stabilized (PS) prosthesis. The purpose of this study was to assess intraoperative kinematics and clinical outcomes of UC and PS rotating platform mobile-bearing TKA. In this randomized controlled study, mobile UC TKA prostheses (n = 45) were compared with mobile PS TKA prostheses (n = 45) with regard to intraoperative kinematics and clinical outcomes. The passive kinematic study using intraoperative navigation system included anterior/posterior translation, varus/valgus alignment and rotation of femur during flexion. The patients were clinically and radiographically evaluated over a 3-year follow-up. Paradoxical anterior translation of the femur was 10.8 ± 5.2 mm in the UC knee from 0° to 82° of knee flexion and 8.7 ± 3.0 mm in the PS knee from 0° to 70° of knee flexion (p = 0.027). Paradoxical internal rotation of the femur was 5.8° in the UC knees and 9.9° in the PS knees (p = 0.003). But, there was no significant difference between the groups in regard to the coronal alignment. There was no significant difference in the range of motion, KS knee scores, KS function scores, and WOMAC index scores. Despite different intraoperative kinematics between mobile UC and mobile PS TKA, neither design reproduced physiologic knee kinematics and there was no difference in clinical outcomes between the two groups. The clinical relevance of the study is that despite different intraoperative kinematics, UC design can be a considerable alternative to PS design in mobile-bearing TKA in respect of clinical outcomes. II.

miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis.

PubMed

Benderska, Natalya; Dittrich, Anna-Lena; Knaup, Sabine; Rau, Tilman T; Neufert, Clemens; Wach, Sven; Fahlbusch, Fabian B; Rauh, Manfred; Wirtz, Ralph M; Agaimy, Abbas; Srinivasan, Swetha; Mahadevan, Vijayalakshmi; Rümmele, Petra; Rapti, Emmanouela; Gazouli, Maria; Hartmann, Arndt; Schneider-Stock, Regine

2015-09-01

Longstanding ulcerative colitis (UC) bears a high risk for development of UC-associated colorectal carcinoma (UCC). The inflammatory microenvironment influences microRNA expression, which in turn deregulates target gene expression. microRNA-26b (miR-26b) was shown to be instrumental in normal tissue growth and differentiation. Thus, we aimed to investigate the impact of miR-26b in inflammation-associated colorectal carcinogenesis. Two different cohorts of patients were investigated. In the retrospective group, a tissue microarray with 38 samples from 17 UC/UCC patients was used for miR-26b in situ hybridization and quantitative reverse transcription polymerase chain reaction analyses. In the prospective group, we investigated miR-26b expression in 25 fresh-frozen colon biopsies and corresponding serum samples of 6 UC and 15 non-UC patients, respectively. In silico analysis, Ago2-RNA immunoprecipitation, luciferase reporter assay, quantitative reverse transcription polymerase chain reaction examination, and miR-26b mimic overexpression were employed for target validation. miR-26b expression was shown to be upregulated with disease progression in tissues and serum of UC and UCC patients. Using miR-26b and Ki-67 expression levels, an UCC was predicted with high accuracy. We identified 4 novel miR-26b targets (DIP1, MDM2, CREBBP, BRCA1). Among them, the downregulation of the E3 ubiquitin ligase DIP1 was closely related to death-associated protein kinase stabilization along the normal mucosa-UC-UCC sequence. In silico functional pathway analysis revealed that the common cellular pathways affected by miR-26b are highly related to cancerogenesis and the development of gastrointestinal diseases. We suggest that miR-26b could serve as a biomarker for inflammation-associated processes in the gastrointestinal system. Because miR-26b expression is downregulated in sporadic colon cancer, it could discriminate between UCC and the sporadic cancer type.

Randomised controlled trial and economic evaluation of the 'Families for Health' programme to reduce obesity in children.

PubMed

Robertson, Wendy; Fleming, Joanna; Kamal, Atiya; Hamborg, Thomas; Khan, Kamran A; Griffiths, Frances; Stewart-Brown, Sarah; Stallard, Nigel; Petrou, Stavros; Simkiss, Douglas; Harrison, Elizabeth; Kim, Sung Wook; Thorogood, Margaret

2017-05-01

Evaluating effectiveness and cost-effectiveness of 'Families for Health V2' (FFH) compared with usual care (UC). Multicentre randomised controlled trial (RCT) (investigators blinded, families unblinded) and economic evaluation. Stratified randomisation by family; target of 120 families. Three National Health Service Primary Care Trusts in West Midlands, England. Overweight or obese (≥91st or ≥98th centile body mass index (BMI)) children aged 6-11 years and their parents/carers, recruited March 2012-February 2014. FFH; a 10-week community-based family programme addressing parenting, lifestyle change and social and emotional development. UC; usual support for childhood obesity at each site. Primary outcomes were 12-months change in children's BMI z-score and incremental cost per quality-adjusted life-year gained (QALY). Secondary outcomes included changes in children's physical activity, fruit and vegetable consumption and quality of life, parents' BMI and mental well-being, family eating/activity, parent-child relationships and parenting style. 115 families (128 children) were randomised to FFH (n=56) or UC (n=59). There was no significant difference in BMI z-score 12-months change (0.114, 95% CI -0.001 to 0.229, p=0.053; p=0.026 in favour of UC with missing value multiple imputation). One secondary outcome, change in children's waist z-score, was significantly different between groups in favour of UC (0.15, 95% CI 0.00 to 0.29). Economic evaluation showed that mean costs were significantly higher for FFH than UC (£998 vs £548, p<0.001). Mean incremental cost-effectiveness of FFH was estimated at £552 175 per QALY. FFH was neither effective nor cost-effective for the management of obesity compared with UC. ISRCTN45032201. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Advanced fuels modeling: Evaluating the steady-state performance of carbide fuel in helium-cooled reactors using FRAPCON 3.4

NASA Astrophysics Data System (ADS)

Hallman, Luther, Jr.

Uranium carbide (UC) has long been considered a potential alternative to uranium dioxide (UO2) fuel, especially in the context of Gen IV gas-cooled reactors. It has shown promise because of its high uranium density, good irradiation stability, and especially high thermal conductivity. Despite its many benefits, UC is known to swell at a rate twice that of UO2. However, the swelling phenomenon is not well understood, and we are limited to a weak empirical understanding of the swelling mechanism. One suggested cladding for UC is silicon carbide (SiC), a ceramic that demonstrates a number of desirable properties. Among them are an increased corrosion resistance, high mechanical strength, and irradiation stability. However, with increased temperatures, SiC exhibits an extremely brittle nature. The brittle behavior of SiC is not fully understood and thus it is unknown how SiC would respond to the added stress of a swelling UC fuel. To better understand the interaction between these advanced materials, each has been implemented into FRAPCON, the preferred fuel performance code of the Nuclear Regulatory Commission (NRC); additionally, the material properties for a helium coolant have been incorporated. The implementation of UC within FRAPCON required the development of material models that described not only the thermophysical properties of UC, such as thermal conductivity and thermal expansion, but also models for the swelling, densification, and fission gas release associated with the fuel's irradiation behavior. This research is intended to supplement ongoing analysis of the performance and behavior of uranium carbide and silicon carbide in a helium-cooled reactor.

Aberrant excitatory rewiring of layer V pyramidal neurons early after neocortical trauma.

PubMed

Takahashi, D Koji; Gu, Feng; Parada, Isabel; Vyas, Shri; Prince, David A

2016-07-01

Lesioned neuronal circuits form new functional connections after a traumatic brain injury (TBI). In humans and animal models, aberrant excitatory connections that form after TBI may contribute to the pathogenesis of post-traumatic epilepsy. Partial neocortical isolation ("undercut" or "UC") leads to altered neuronal circuitry and network hyperexcitability recorded in vivo and in brain slices from chronically lesioned neocortex. Recent data suggest a critical period for maladaptive excitatory circuit formation within the first 3days post UC injury (Graber and Prince 1999, 2004; Li et al. 2011, 2012b). The present study focuses on alterations in excitatory connectivity within this critical period. Immunoreactivity (IR) for growth-associated protein (GAP)-43 was increased in the UC cortex 3days after injury. Some GAP-43-expressing excitatory terminals targeted the somata of layer V pyramidal (Pyr) neurons, a domain usually innervated predominantly by inhibitory terminals. Immunocytochemical analysis of pre- and postsynaptic markers showed that putative excitatory synapses were present on somata of these neurons in UC neocortex. Excitatory postsynaptic currents from UC layer V Pyr cells displayed properties consistent with perisomatic inputs and also reflected an increase in the number of synaptic contacts. Laser scanning photostimulation (LSPS) experiments demonstrated reorganized excitatory connectivity after injury within the UC. Concurrent with these changes, spontaneous epileptiform bursts developed in UC slices. Results suggest that aberrant reorganization of excitatory connectivity contributes to early neocortical hyperexcitability in this model. The findings are relevant for understanding the pathophysiology of neocortical post-traumatic epileptogenesis and are important in terms of the timing of potential prophylactic treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis.

PubMed

Sargın, Zeynep Gök; Erin, Nuray; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients' demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis

PubMed Central

Sargın, Zeynep Gök; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC. PMID:29232715

Beverage consumption and risk of ulcerative colitis: Systematic review and meta-analysis of epidemiological studies.

PubMed

Nie, Jia-Yan; Zhao, Qiu

2017-12-01

Epidemiological studies have provided controversial evidence between beverage consumption and the risk of ulcerative colitis (UC). This study aimed to determine the role of beverage consumption in the development of UC. A systematic search was conducted in public databases to identify all relevant studies, and study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Sixteen studies were identified with a total of 3689 cases and 335,339 controls. Alcohol consumption showed no significant association with UC risk (RR for the highest vs the lowest consumption level: 0.95, 95% CI: 0.65-1.39). Coffee consumption tended to be inversely associated with UC risk (RR: 0.58, 95% CI: 0.33-1.05), but it was not significant and confounded by smoking adjustment. Soft drinks consumption was associated with UC risk (RR: 1.69, 95% CI: 1.24-2.30), and tea consumption was inversely associated with UC risk (RR: 0.69, 95% CI: 0.58-0.83). In conclusion, high consumption of soft drinks might increase the risk of UC, while tea consumption might decrease the risk.

The Role of Triplet Exciton Diffusion in Light-Upconverting Polymer Glasses.

PubMed

Raišys, Steponas; Kazlauskas, Karolis; Juršėnas, Saulius; Simon, Yoan C

2016-06-22

Light upconversion (UC) via triplet-triplet annihilation (TTA) by using noncoherent photoexcitation at subsolar irradiance power densities is extremely attractive, particularly for enhanced solar energy harvesting. Unfortunately, practical TTA-UC application is hampered by low UC efficiency of upconverting polymer glasses, which is commonly attributed to poor exciton diffusion of the triplet excitons across emitter molecules. The present study addresses this issue by systematically evaluating triplet exciton diffusion coefficients and diffusion lengths (LD) in a UC model system based on platinum-octaethylporphyrin-sensitized poly(methyl methacrylate)/diphenylanthracene (emitter) films as a function of emitter concentration (15-40 wt %). For this evaluation time-resolved photoluminescence bulk-quenching technique followed by Stern-Volmer-type quenching analysis of experimental data was employed. The key finding is that although increasing emitter concentration in the disordered PMMA/DPA/PtOEP films improves triplet exciton diffusion, and thus LD, this does not result in enhanced UC quantum yield. Conversely, improved LD accompanied by the accelerated decay of UC intensity on millisecond time scale degrades TTA-UC performance at high emitter loadings (>25 wt %) and suggests that diffusion-enhanced nonradiative decay of triplet excitons is the major limiting factor.

Genetic polymorphisms in the IL-18 gene and ulcerative colitis risk: a meta-analysis.

PubMed

Wang, Ying; Tong, Jing; Chang, Bing; Wang, Bai-Fang; Zhang, Dai; Wang, Bing-Yuan

2014-07-01

This meta-analysis was performed to evaluate the relationships between genetic polymorphisms in the IL-18 gene and ulcerative colitis (UC) risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with their 95% confidence intervals (95% CI) were calculated. Eight case-control studies with a total of 1000 UC cases and 1392 healthy subjects met the inclusion criteria. Six common polymorphisms in the IL-18 gene were evaluated, including rs1946518 A>C, rs187238 G>C, rs917997 G>A, Codon35, rs1946519 C>A, and rs360718 A>C. The results of our meta-analysis suggest that the IL-18 rs1946518 (allele model: OR=1.22, 95% CI: 1.01-1.48, p=0.039; dominant model: OR=1.44, 95% CI: 1.01-2.06, p=0.045; respectively), rs187238 (allele model: OR=1.38, 95% CI: 1.19-1.61, p<0.001; dominant model: OR=1.50, 95% CI: 1.03-2.19, p=0.034; respectively), and rs360718 (allele model: OR=2.18, 95% CI: 1.22-3.90, p=0.008) polymorphisms might be strongly correlated with an increased risk of UC. A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's risk of UC. Our results revealed positive significant correlations between IL-18 genetic polymorphisms and an increased risk of UC among Asians (allele model: OR=1.36, 95% CI: 1.16-1.60, p<0.001; dominant model: OR=1.50, 95% CI: 1.14-1.98, p=0.004; respectively) and Africans (allele model: OR=1.45, 95% CI: 1.03-2.05, p=0.034), but not among Caucasians (all p>0.05). Our findings provide convincing evidence that IL-18 genetic polymorphisms may contribute to susceptibility to UC, especially the rs1946518, rs187238, and rs360718 polymorphisms among Asians and Africans.

Comparison of post-operative intravesical recurrence and oncological outcomes after open versus laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma.

PubMed

Zou, Lujia; Zhang, Limin; Zhang, Hu; Jiang, Haowen; Ding, Qiang

2014-04-01

To retrospectively evaluate intravesical recurrence and oncological outcomes after open or laparoscopic radical nephroureterectomy (RNU) for the upper urinary tract urothelial carcinoma (UUT-UC). This study comprised 122 patients diagnosed UUT-UC and subsequently nephroureterectomy was performed on. Several clinical and pathological parameters were emphasized for comparison of clinical outcomes. Among 122 patients with UUT-UC, 101 (82.8 %) and 21 (17.2 %) underwent open or laparoscopic radical nephroureterectomy (ONU or LNU), respectively. In univariable and multivariable Cox regression models, the surgical procedure exerted an impact neither on post-operative intravesical recurrence rate (p = 0.179 and 0.213, respectively) nor on cancer-specific mortality rate (p = 0.561 and 0.159, respectively). The 1-, 2- and 5-year cancer-specific survival (CSS) rates of patients undergoing ONU or LNU were 92.1 versus 95.2 %, 87.1 versus 90.5 %, 79.2 versus 85.7 %, respectively, and the Kaplan–Meier plot illustrated that patients from two groups enjoyed an equivalent survival rate (p = 0.559). Moreover, we added that previous history of bladder tumor and pre-operative hydronephrosis was associated with intravesical recurrence, whereas three prognostic factors, including pathological tumor stage, grade, and lymphovascular invasion, showed possibility to be predictors of cancer-specific mortality. There existed no significant difference of intravesical recurrence and CSS between patients after ONU and LNU. Conclusively, laparoscopic radical nephroureterectomy did not present superiority to open management for patients with UUT-UC.

Assessing the Impact of Surgeon Experience on Urinary Continence Recovery After Robot-Assisted Radical Prostatectomy: Results of Four High-Volume Surgeons.

PubMed

Fossati, Nicola; Di Trapani, Ettore; Gandaglia, Giorgio; Dell'Oglio, Paolo; Umari, Paolo; Buffi, Nicolò Maria; Guazzoni, Giorgio; Mottrie, Alexander; Gaboardi, Franco; Montorsi, Francesco; Briganti, Alberto; Suardi, Nazareno

2017-09-01

To test the impact of surgeon experience on urinary continence (UC) recovery after robot-assisted radical prostatectomy (RARP). The study included 1477 consecutive patients treated with RARP by four surgeons between 2006 and 2014. UC recovery was defined as being completely dry over a 24-hour period at follow-up. Surgeon experience was coded as the total number of RARP performed by the surgeon before the patient's operation. Multivariable analysis tested the association between surgeon experience and UC recovery. Covariates consisted of patient age, Charlson comorbidity index, preoperative International Index of Erectile Function-Erectile Function domain (IIEF-EF), nerve-sparing surgery (none vs unilateral vs bilateral), and preoperative risk groups (low- vs intermediate- vs high risk). The number of cases performed by each surgeon was 541, 413, 411, and 112, respectively. Median follow-up was 24 months (inter-quartile range: 18, 40). The UC recovery rate at 1 year after surgery was 82%. At multivariable analyses, surgeon experience represented an independent predictor of UC recovery (hazard ratio: 1.02, p < 0.001). The surgical learning curve was similar among surgeons, moving linearly from ∼60% of UC rate at the initial cases to almost 90% after more than 400 procedures. In patients undergoing RARP, surgeon experience is a significant predictor of UC recovery. The surgical learning curve of UC recovery does not reach a plateau even after more than 100 cases, suggesting a continuous improvement of the surgical technique. These findings deserve attention for patient counseling and future comparative studies evaluating functional outcomes after RARP.

Low prevalence of Blastocystis sp. in active ulcerative colitis patients.

PubMed

Rossen, N G; Bart, A; Verhaar, N; van Nood, E; Kootte, R; de Groot, P F; D'Haens, G R; Ponsioen, C Y; van Gool, T

2015-05-01

Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5-49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0-37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls.

IBS-like symptoms in patients with ulcerative colitis

PubMed Central

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted. PMID:25733921

IBS-like symptoms in patients with ulcerative colitis.

PubMed

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain-gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain-gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted.

Prediction of zeolite-cement-sand unconfined compressive strength using polynomial neural network

NASA Astrophysics Data System (ADS)

MolaAbasi, H.; Shooshpasha, I.

2016-04-01

The improvement of local soils with cement and zeolite can provide great benefits, including strengthening slopes in slope stability problems, stabilizing problematic soils and preventing soil liquefaction. Recently, dosage methodologies are being developed for improved soils based on a rational criterion as it exists in concrete technology. There are numerous earlier studies showing the possibility of relating Unconfined Compressive Strength (UCS) and Cemented sand (CS) parameters (voids/cement ratio) as a power function fits. Taking into account the fact that the existing equations are incapable of estimating UCS for zeolite cemented sand mixture (ZCS) well, artificial intelligence methods are used for forecasting them. Polynomial-type neural network is applied to estimate the UCS from more simply determined index properties such as zeolite and cement content, porosity as well as curing time. In order to assess the merits of the proposed approach, a total number of 216 unconfined compressive tests have been done. A comparison is carried out between the experimentally measured UCS with the predictions in order to evaluate the performance of the current method. The results demonstrate that generalized polynomial-type neural network has a great ability for prediction of the UCS. At the end sensitivity analysis of the polynomial model is applied to study the influence of input parameters on model output. The sensitivity analysis reveals that cement and zeolite content have significant influence on predicting UCS.

Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls.

PubMed

Kleessen, B; Kroesen, A J; Buhr, H J; Blaut, M

2002-09-01

Endogenous intestinal bacteria and/or specific bacterial pathogens are suspected of being involved in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to investigate IBD tissues for different bacterial population groups harbouring the mucosal surface and/or invading the mucosa. Tissue sections from surgical resections from the terminal ileum and/or the colon from 24 IBD patients (12 active ulcerative colitis (UC), 12 active Crohn disease (CD)) and 14 non-IBD controls were studied by fluorescent in situ hybridization on a quantifiable basis. More bacteria were detected on the mucosal surface of IBD patients than on those of non-IBD controls (P < 0.05). Bacterial invasion of the mucosa was evident in 83.3% of colonic specimens from the UC patients, in 55.6% of the ileal and in 25% of the colonic specimens from the CD patients, but no bacteria were detected in the tissues of the controls. Colonic UC specimens were colonized by a variety of organisms, such as bacteria belonging to the gamma subdivision of Proteobacteria, the Enterobacteriaceae, the Bacteroides/Prevotella cluster, the Clostridium histolyticum/Clostridium lituseburense group, the Clostridium coccoides/Eubacterium rectale group, high G + C Gram-positive bacteria, or sulphate-reducing bacteria, while CD samples harboured mainly bacteria belonging to the former three groups. Pathogenic events in CD and UC may be associated with different alterations in the mucosal flora of the ileum and colon.

Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis

PubMed Central

Tahara, Tomomitsu; Hirata, Ichiro; Nakano, Naoko; Tahara, Sayumi; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Yamada, Hyuga; Yoshida, Dai; Ohmori, Takafumi; Maeda, Kohei; Komura, Naruomi; Ikuno, Hirokazu; Jodai, Yasutaka; Kamano, Toshiaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Tuskamoto, Tetsuya; Urano, Makoto; Shibata, Tomoyuki; Kuroda, Makoto; Ohmiya, Naoki

2017-01-01

BACKGROUND AND AIM Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of >450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/neg) samples (P<0.01). Genes hypermethylated in FB-high samples included well-known type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC. PMID:28977914

Surgical Outcomes in Vedolizumab-Treated Patients with Ulcerative Colitis.

PubMed

Lightner, Amy L; McKenna, Nicholas P; Moncrief, Sara; Pemberton, John H; Raffals, Laura E; Mathis, Kellie L

2017-12-01

Surgical outcomes and pouch outcomes in the setting of vedolizumab remains poorly understood. We sought to determine the rate of 30-day postoperative surgical infectious complications and pouch-specific complications among patients with ulcerative colitis (UC) who received vedolizumab within 12 weeks of surgery. A retrospective chart review between 5/1/2014 and 12/31/2016 of all adult patients with UC who underwent an abdominal operation was performed. Patients with UC who received vedolizumab within 12 weeks of their abdominal operation were compared with patients with UC on anti-TNFα treatment. Eighty-eight patients received vedolizumab and 62 received anti-TNFα within 12 weeks of surgery. More vedolizumab-treated patients had superficial surgical site infections (P = 0.047) and mucocutaneous separation at the ileostomy (P = 0.047), but there was no difference in the overall surgical infectious complication rate, deep space SSI, 30-day hospital readmission or return to the operating room. On univariate analysis of SSI among patients with UC, exposure to vedolizumab was not a significant predictor of SSI (P = 0.27), but steroids were predictive of SSI on univariate (P = 0.02) and multivariable analysis (P = 0.02). After ileal pouch anal anastomosis, there was a higher rate of intra-abdominal abscesses (31.3% versus 5.9%) and mucocutaneous separation (18.8% versus 0%) in the vedolizumab group compared with the anti-TNFα group, but statistical significance was not reached. Vedolizumab patients had significantly increased rates of superficial SSI, but not overall infectious complications. Among ileal pouch anal anastomosis patients, peripouch abscess rates were increased among vedolizumab-treated patients, but this did not reach statistical significance. Vedolizumab seems safe in the perioperative period for patients with UC.

Role of moxibustion in inflammatory responses during treatment of rat ulcerative colitis

PubMed Central

Han, Yang; Ma, Tie-Ming; Lu, Mao-Lin; Ren, Lu; Ma, Xian-De; Bai, Zeng-Hua

2014-01-01

AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-κB p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 ± 0.54 vs 1.20 ± 0.44, 0.60 ± 0.54 vs 1.80 ± 0.45, 0.60 ± 0.54 vs 3.0 ± 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 ± 8.75 vs 76.61 ± 3.58, 105.46 ± 8.75 vs 69.78 ± 1.87, 105.46 ± 8.75 vs 67.41 ± 1.84, respectively, P < 0.01 for IL-8; and 30.83 ± 1.29 vs 75.64 ± 1.90, 30.83 ± 1.29 vs 80.90 ± 3.16, 30.83 ± 1.29 vs 83.46 ± 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-κB p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 ± 0.026 vs 0.380 ± 0.022, 0.492 ± 0.026 vs 0.355 ± 0.005, 0.492 ± 0.026 vs 0.327 ± 0.015, respectively, P < 0.05 for TLR9; and 0.436 ± 0.041 vs 0.326 ± 0.022, 0.436 ± 0.041 vs 0.293 ± 0.006, 0.436 ± 0.041 vs 0.265 ± 0.017, respectively, P < 0.05 for NF-κB p65). CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-κB p65 in UC rats. PMID:25170214

Role of moxibustion in inflammatory responses during treatment of rat ulcerative colitis.

PubMed

Han, Yang; Ma, Tie-Ming; Lu, Mao-Lin; Ren, Lu; Ma, Xian-De; Bai, Zeng-Hua

2014-08-28

To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-κB p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 ± 0.54 vs 1.20 ± 0.44, 0.60 ± 0.54 vs 1.80 ± 0.45, 0.60 ± 0.54 vs 3.0 ± 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 ± 8.75 vs 76.61 ± 3.58, 105.46 ± 8.75 vs 69.78 ± 1.87, 105.46 ± 8.75 vs 67.41 ± 1.84, respectively, P < 0.01 for IL-8; and 30.83 ± 1.29 vs 75.64 ± 1.90, 30.83 ± 1.29 vs 80.90 ± 3.16, 30.83 ± 1.29 vs 83.46 ± 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-κB p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 ± 0.026 vs 0.380 ± 0.022, 0.492 ± 0.026 vs 0.355 ± 0.005, 0.492 ± 0.026 vs 0.327 ± 0.015, respectively, P < 0.05 for TLR9; and 0.436 ± 0.041 vs 0.326 ± 0.022, 0.436 ± 0.041 vs 0.293 ± 0.006, 0.436 ± 0.041 vs 0.265 ± 0.017, respectively, P < 0.05 for NF-κB p65). Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-κB p65 in UC rats.

CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis.

PubMed

Zhao, Jia-Jun; Wang, Di; Yao, Hui; Sun, Da-Wei; Li, Hong-Yu

2015-09-14

To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk. PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran's Q-statistic and I(2) tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger's linear regression test were inspected for indication of publication bias. A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222-1.886, P < 0.001). CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk.

[Use of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases].

PubMed

Lazebnik, L B; Konopliannikov, A G; Kniazev, O V; Parfenov, A I; Tsaregorodtseva, T M; Ruchkina, I N; Khomeriki, S G; Rogozina, V A; Konopliannikova, O A

2010-01-01

to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID). Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn's disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn's disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2) x 10(8) tells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion. A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comporison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only. The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial.

PubMed

Lang, Alon; Salomon, Nir; Wu, Justin C Y; Kopylov, Uri; Lahat, Adi; Har-Noy, Ofir; Ching, Jessica Y L; Cheong, Pui Kuan; Avidan, Benjamin; Gamus, Dorit; Kaimakliotis, Ioannis; Eliakim, Rami; Ng, Siew C; Ben-Horin, Shomron

2015-08-01

The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC. We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded. In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups. Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

PubMed

Rosario, M; Dirks, N L; Gastonguay, M R; Fasanmade, A A; Wyant, T; Parikh, A; Sandborn, W J; Feagan, B G; Reinisch, W; Fox, I

2015-07-01

Vedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3). © 2015 Takeda Pharmaceuticals International Co published by John Wiley & Sons Ltd.

Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

PubMed

Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

2010-08-01

The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Intestinal protozoa infections among patients with ulcerative colitis: prevalence and impact on clinical disease course.

PubMed

Yamamoto-Furusho, Jesús K; Torijano-Carrera, Emma

2010-01-01

Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of inflammatory bowel disease. To explore the prevalence of intestinal protozoa in patients with ulcerative colitis (UC) and its impact on clinical disease course. A total of 215 patients with definitive diagnosis of UC were studied. Fresh feces samples taken from all UC patients were examined immediately using trichrome-staining methods. A total of 103 female and 112 male UC patients were analyzed. The mean age at diagnosis was 30.5 +/- 10.8 years. The prevalence of overall parasitic infections was 24% and distributed as follows: Blastocystis hominis in 22 patients (10%), Endolimax nana in 19 cases (9%), and Entamoebahistolytica in 11 cases (5%). A significantly increased frequency of protozoa infection was found in those patients with persistent activity and intermittent activity as compared to active than inactive group (p = 1 x 10(-7), OR 13.05, 95% CI 4.28-42.56, and p = 0.003, OR 1.42-14.47, respectively). Interestingly, this association remained significant when we compared the persistent activity group versus intermittent activity group (p = 0.003, OR 2.97, 95% CI 1.35-6.59). Subgroup analysis showed no association between protozoa infection (E. histolytica, B. hominis, and E. nana) and other clinical variables such as gender, extent of disease, extraintestinal complications, medical treatment and grade of disease activity. The prevalence of intestinal protozoa infections in Mexican UC patients was 24% and these microorganisms could be a contributing cause of persistent activity despite medical treatment in our population. 2010 S. Karger AG, Basel.

Assessment of Atrial Electromechanical Delay and Left Atrial Mechanical Functions in Patients with Ulcerative Colitis.

PubMed

Nar, Gokay; Ergul, Bilal; Aksan, Gokhan; Inci, Sinan

2016-07-01

Ulcerative colitis (UC) is a common inflammatory bowel disease causing systemic inflammation, which may also affect the cardiovascular system, as well as other organ systems. The aim of the current study was to evaluate left atrial (LA) mechanical functions and duration of atrial electromechanical delay (AEMD) with echocardiography in patients with UC. A total of 91 patients, 45 with UC (Group 1) and 46 healthy individuals as control (Group 2) were included in the study. The demographic and laboratory data were recorded, and echocardiographic measurements were taken for all patients. In the evaluation of basal clinical and laboratory findings, no difference was detected between the two groups, except for white blood cell count (WBC) (8.26 ± 2.71 vs. 7.06 ± 1.70, P = 0.013) and high-sensitivity C-reactive protein (Hs-CRP; 3.4 ± 1.7 vs. 1.0 ± 0.8, P < 0.001). The echocardiographic assessment revealed that the diastolic parameters such as E-, E/A-, and E- waves decreased in the UC group when compared to the control group. LA mechanical functions were different between groups, except for left atrial (LA) maximal volume: LA minimum volume (22.2 ± 12.9 vs. 15.3 ± 4.7, P = 0.001), LA volume before atrial systole (29.9 ± 14.2 vs. 24.2 ± 4.9, P = 0.021), LA ejection fraction (27.4 ± 16.5 vs. 38.6 ± 10.1, P < 0.001), LA total emptying volume (17.9 ± 6.9 vs. 21.9 ± 5.9, P = 0.004), LA active emptying fraction (27.4 ± 16.5 vs. 38.6 ± 10.1, P < 0.001), LA active emptying volume (7.7 ± 3.6 vs. 9.4 ± 2.9, P = 0.013), LA passive emptying fraction (26.8 ± 10.2 vs. 33.2 ± 9.2, P = 0.002), and LA passive emptying volume (10.3 ± 4.9 vs. 12.5 ± 4.5, P = 0.029). There was a significant difference between the groups in terms of AEMD durations, except time interval from the onset of the P-wave on the surface ECG to the peak of the late diastolic wave (PA) of the tricuspid valve. The correlation analysis revealed that age and duration of disease were correlated with AEMD. The current study reported that LA volume and mechanical functions degenerated and AEMD increased in patients with UC when compared to the control group. These findings demonstrate that UC may have effects on LA electromechanical functions related to duration of disease. © 2016, Wiley Periodicals, Inc.

Nationwide analysis on the impact of socioeconomic land use factors and incidence of urothelial carcinoma.

PubMed

Brandt, Maximilian P; Gust, Kilian M; Mani, Jens; Vallo, Stefan; Höfner, Thomas; Borgmann, Hendrik; Tsaur, Igor; Thomas, Christian; Haferkamp, Axel; Herrmann, Eva; Bartsch, Georg

2018-02-01

Incidence rates for urothelial carcinoma (UC) have been reported to differ between countries within the European Union (EU). Besides occupational exposure to chemicals, other substances such as tobacco and nitrite in groundwater have been identified as risk factors for UC. We investigated if regional differences in UC incidence rates are associated with agricultural, industrial and residential land use. Newly diagnosed cases of UC between 2003 and 2010 were included. Information within 364 administrative districts of Germany from 2004 for land use factors were obtained and calculated as a proportion of the total area of the respective administrative district and as a smoothed proportion. Furthermore, information on smoking habits was included in our analysis. Kulldorff spatial clustering was used to detect different clusters. A negative binomial model was used to test the spatial association between UC incidence as a ratio of observed versus expected incidence rates, land use and smoking habits. We identified 437,847,834 person years with 171,086 cases of UC. Cluster analysis revealed areas with higher incidence of UC than others (p=0.0002). Multivariate analysis including significant pairwise interactions showed that the environmental factors were independently associated with UC (p<0.001). The RR was 1.066 (95% CI 1.052-1.080), 1.066 (95% CI 1.042-1.089) and 1.067 (95% CI 1.045-1.093) for agricultural, industrial and residential areas, respectively, and 0.996 (95% CI 0.869-0.999) for the proportion of never smokers. This study displays regional differences in incidence of UC in Germany. Additionally, results suggest that socioeconomic factors based on agricultural, industrial and residential land use may be associated with UC incidence rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intermittent granulocyte and monocyte apheresis versus mercaptopurine for maintaining remission of ulcerative colitis: a pilot study.

PubMed

Sakuraba, Atsushi; Sato, Toshiro; Morohoshi, Yuichi; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Takaishi, Hiromasa; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi

2012-06-01

The effect of granulocyte and monocyte adsorption apheresis (GMA) on prevention of relapse of ulcerative colitis (UC) is not clear. This was a pilot open-labeled, prospective, randomized, unblinded study to compare the tolerability and efficacy of intermittent GMA (once every 2 weeks) with mercaptopurine to maintain remission of UC. Twenty-one patients with UC, who had achieved remission by induction therapies were randomly assigned to receive either intermittent GMA (N = 10) or oral mercaptopurine (0.5 mg/kg per day; N = 11). The study period was 24 months. The rate of the patients maintaining remission and the incidences of adverse effects were compared between the two groups. At 24 months, seven of 10 patients (70.0%) on intermittent GMA and seven of 11 patients (63.6%, P = 1.00) on oral mercaptopurine were still in remission. Three patients relapsed in each group. One patient taking mercaptopurine, but none receiving intermittent GMA, dropped out because of adverse effects. Intermittent therapy with GMA was well tolerated and a substantial proportion of patients maintained remission. Intermittent GMA therapy in maintaining remission of UC merits further investigation. © 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.

JAK2 rs10758669 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis.

PubMed

Zhang, Ji-Xiang; Song, Jia; Wang, Jun; Dong, Wei-Guo

2014-06-01

In this meta-analysis, we aimed to clarify the impact of Janus kinase 2 (JAK2) rs10758669 polymorphisms on ulcerative colitis (UC) and Crohn's disease (CD) risk. Data were extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95%CIs) were calculated. Eleven studies with 7009 CD patients, 7929 UC patients, and 19235 controls were included. The results showed that JAK2 rs10758669 polymorphism was associated with CD (AC vs. AA, OR = 1.16, 95%CI, 1.08-1.24; CC vs. AA, OR = 1.29, 95%CI, 1.17-1.43; AC + CC vs. AA, OR = 1.19, 95%CI, 1.11-1.27; CC vs. AA + AC, OR = 1.19, 95%CI, 1.09-1.31; C vs. A, OR = 1.14, 95%CI, 1.09-1.20) and UC susceptibility (AC vs. AA, OR = 1.14, 95%CI, 1.06-1.22; CC vs. AA, OR = 1.33, 95%CI, 1.20-1.47; AC + CC vs. AA, OR = 1.18, 95%CI, 1.10-1.27; CC vs. AA + AC, OR = 1.24, 95%CI, 1.12-1.36; C vs. A, OR = 1.15, 95%CI, 1.10-1.21). But no significant association was found between JAK2 rs10758669 polymorphism with CD in Asian. Either in adult-onset group or multi-age group, hospital-based group or population-based group, JAK2 rs10758669 polymorphism was associated with CD and UC susceptibility. This meta-analysis indicated that JAK2 rs10758669 polymorphism was a risk factor both for CD and UC, especially in Caucasian. The differences in age of onset and study design did not influence the associations obviously. Gene-gene and gene-environment interactions should be investigated in the future.

Mass-imbalanced ionic Hubbard chain

NASA Astrophysics Data System (ADS)

Sekania, Michael; Baeriswyl, Dionys; Jibuti, Luka; Japaridze, George I.

2017-07-01

A repulsive Hubbard model with both spin-asymmetric hopping (t↑≠t↓ ) and a staggered potential (of strength Δ ) is studied in one dimension. The model is a compound of the mass-imbalanced (t↑≠t↓ ,Δ =0 ) and ionic (t↑=t↓ ,Δ >0 ) Hubbard models, and may be realized by cold atoms in engineered optical lattices. We use mostly mean-field theory to determine the phases and phase transitions in the ground state for a half-filled band (one particle per site). We find that a period-two modulation of the particle (or charge) density and an alternating spin density coexist for arbitrary Hubbard interaction strength, U ≥0 . The amplitude of the charge modulation is largest at U =0 , decreases with increasing U and tends to zero for U →∞ . The amplitude for spin alternation increases with U and tends to saturation for U →∞ . Charge order dominates below a value Uc, whereas magnetic order dominates above. The mean-field Hamiltonian has two gap parameters, Δ↑ and Δ↓, which have to be determined self-consistently. For U Uc they have different signs, and for U =Uc one gap parameter jumps from a positive to a negative value. The weakly first-order phase transition at Uc can be interpreted in terms of an avoided criticality (or metallicity). The system is reluctant to restore a symmetry that has been broken explicitly.

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

PubMed

van den Heuvel, E G H M; van Schoor, N M; Vermeer, C; Zwijsen, R M L; den Heijer, M; Comijs, H C

2015-11-01

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. Longitudinal study with six years follow-up. Community based. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Mutational Hotspots in the Mitochondrial D-Loop Region of Cancerous and Precancerous Colorectal Lesions in Egyptian Patients

PubMed Central

El-Guendy, Nadia; Tantawy, Marwa; Abdelhady, Hala; El-Ghor, Akmal; Abdel Wahab, Abdel Hady

2011-01-01

Mutations in the mitochondrial genome (mtDNA) are associated with different types of cancer, specifically colorectal cancer (CRC). However, few studies have been performed on precancerous lesions, such as ulcerative colitis (UC) lesions and adenomatous polyps (AP). The aim of this study was to identify mtDNA mutations in the cancerous and precancerous lesions of Egyptian patients. An analysis of the mutations found in six regions of the mtDNA genome (ND1, ND5, COI, tRNAser, D-loop 1, and 2) in 80 Egyptian patients (40 CRC, 20 UC, and 20 AP) was performed using polymerase chain reaction–single-strand conformational polymorphism techniques and followed up by direct sequencing. The overall incidence of mutations was 25%, 25%, and 35% in CRC, UC, and AP cases, respectively. Although there was no common mutation pattern within each group, a large number of mutations were detected in the D-loop region in all of the groups. Some mutations (e.g., T414G) were detected repeatedly in precancerous (UC and AP) and cancerous lesions. Mutations detected in patients with CRC were predominantly found in the ND1 gene (40%). Our preliminary study suggests that Egyptian patients with CRC have a large number of mtDNA mutations, especially in the D-loop region, which have not been previously reported. Mutations in the mtDNA of precancerous lesions (i.e., AP and UC) may contribute to transformation events that lead to CRC. PMID:21612400

Assessment of selected psychological factors in patients with inflammatory bowel disease

PubMed Central

Kaczówka, Anna; Jeżewska, Maria

2015-01-01

Introduction In the majority of patients with inflammatory bowel diseases (IBD) mental health problems are demonstrated in the form of excessive anxiety and unstable emotional reactions. Emotional instability affects the wellbeing of these patients, and also their attitude towards the disease and the course of treatment. Aim The objective of the study is to evaluate psychological factors in patients with IBD, and to compare patients with ulcerative colitis (UC) and patients suffering from Crohn's disease (CD) with respect to intensity of these factors. Material and methods The study included 108 patients with IBD. NEO-FFI and type-D Scale were used to evaluate personality traits. Anxiety level was measured with STAI. CECS was used to measure the patients’ tendency to suppress negative emotions. Results In the patients with CD 45% of subjects presented type D personality. In the group of patients with UC, type D personality was found in 38%. The higher levels of neuroticism and extraversion were observed in patients with UC, whereas the patients with CD exhibited a higher level of openness to experience and agreeableness. In patients with CD the levels of state anxiety were elevated, whereas in patients with UC higher scores were both for state and trait anxiety. Conclusions There were no statistically significant differences in terms of personality factors in a group of patients with CD and UC. It was found that the majority of patients with IBD suffer elevated or high sense of anxiety. PMID:27110311

CAMPARE and Cal-Bridge: Two Institutional Networks Increasing Diversity in Astronomy

NASA Astrophysics Data System (ADS)

Rudolph, Alexander L.; Impey, Chris David; Smecker-Hane, Tammy A.

2016-01-01

We describe two programs, CAMPARE and Cal-Bridge, with the common mission of increasing participation of groups traditionally underrepresented in astronomy, through summer research opportunities, in the case of CAMPARE, scholarships in the case of Cal-Bridge, and significant mentoring in both programs, leading to an increase in their numbers successfully pursuing a PhD in the field.In 6 years, the CAMPARE program has sent 62 students, >85% from underrepresented groups, to conduct summer research at one of twelve major research institutions in California, Arizona, and Wyoming. The graduation rate among CAMPARE scholars is 97%, and of the 37 CAMPARE scholars who have graduated with a Bachelor's degree, almost 60% (21) have completed or are pursuing graduate education in astronomy or a related field, at institutions including UCLA, USC, UC Riverside, Stanford, Univ. of Rochester, Georgia Tech, Kent State, Indiana Univ., Univ. of Oregon, Syracuse, and the Fisk-Vanderbilt Master's-to-PhD program. The Cal-Bridge program is a CSU-UC Bridge program comprised of faculty form 5 University of California (UC), 8 California State University (CSU), and 8 California Community College (CCC) campuses in Southern California. Cal-Bridge provides much deeper mentoring and professional development experiences over the last two years of undergraduate and first year of graduate school to students from this diverse network of higher education institutions. Cal-Bridge Scholars benefit from financial support, intensive, joint mentoring by CSU and UC faculty, professional development workshops, and exposure to research opportunities at the participating UC campuses.

Long Noncoding RNA uc002yug.2 Activates HIV-1 Latency through Regulation of mRNA Levels of Various RUNX1 Isoforms and Increased Tat Expression.

PubMed

Huan, Chen; Li, Zhaolong; Ning, Shanshan; Wang, Hong; Yu, Xiao-Fang; Zhang, Wenyan

2018-05-01

The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long noncoding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. In this study, we demonstrated that lncRNA uc002yug.2 plays a key role in HIV-1 replication and latency. uc002yug.2 potentially enhances HIV-1 replication, long terminal repeat (LTR) activity, and the activation of latent HIV-1 in both cell lines and CD4 + T cells from patients. Further investigation revealed that uc002yug.2 activates latent HIV-1 through downregulating RUNX1b and -1c and upregulating Tat protein expression. The accumulated evidence supports our model that the Tat protein has the key role in the uc002yug.2-mediated regulatory effect on HIV-1 reactivation. Moreover, uc002yug.2 showed an ability to activate HIV-1 similar to that of suberoylanilide hydroxamic acid or phorbol 12-myristate 13-acetate using latently infected cell models. These findings improve our understanding of lncRNA regulation of HIV-1 replication and latency, providing new insights into potential targeted therapeutic interventions. IMPORTANCE The latent viral reservoir is the primary obstacle to curing HIV-1 disease. To date, only a few lncRNAs, which play major roles in various biological processes, including viral infection, have been identified as regulators in HIV-1 latency. In this study, we demonstrated that lncRNA uc002yug.2 is important for both HIV-1 replication and activation of latent viruses. Moreover, uc002yug.2 was shown to activate latent HIV-1 through regulating alternative splicing of RUNX1 and increasing the expression of Tat protein. These findings highlight the potential merit of targeting lncRNA uc002yug.2 as an activating agent for latent HIV-1. Copyright © 2018 American Society for Microbiology.

Fecal immunochemical test for predicting mucosal healing in ulcerative colitis patients: A systematic review and meta-analysis.

PubMed

Dai, Cong; Jiang, Min; Sun, Ming-Jun; Cao, Qin

2018-05-01

Fecal immunochemical test (FIT) is a promising marker for assessment of inflammatory bowel disease activity. However, the utility of FIT for predicting mucosal healing (MH) of ulcerative colitis (UC) patients has yet to be clearly demonstrated. The objective of our study was to perform a diagnostic test accuracy test meta-analysis evaluating the diagnostic accuracy of FIT in predicting MH of UC patients. We systematically searched the databases from inception to November 2017 that evaluated MH in UC. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Six studies comprising 625 UC patients were included in the meta-analysis. The pooled sensitivity and specificity values for predicting MH in UC were 0.77 (95% confidence interval [CI], 0.72-0.81) and 0.81 (95% CI, 0.76-0.85), respectively. The FIT level had a high rule-in value (positive likelihood ratio, 3.79; 95% CI, 2.85-5.03) and a moderate rule-out value (negative likelihood ratio, 0.26; 95% CI, 0.16-0.43) for predicting MH in UC. The results of the receiver operating characteristic curve analysis (area under the curve, 0.88; standard error of the mean, 0.02) and diagnostic odds ratio (18.08; 95% CI, 9.57-34.13) also revealed improved discrimination for identifying MH in UC with FIT concentration. Our meta-analysis has found that FIT is a simple, reliable non-invasive marker for predicting MH in UC patients. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis

PubMed Central

Wang, Ming-Hsi; Fiocchi, Claudio; Zhu, Xiaofeng; Ripke, Stephan; Kamboh, M. Ilyas; Rebert, Nancy; Duerr, Richard H.; Achkar, Jean-Paul

2014-01-01

Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust Case-Control Consortium (WTCCC) IBD GWAS was used as a replication cohort. We applied logic regression (LR), a novel adaptive regression methodology, to search for high order interactions. Exploratory genotype correlations with UC sub-phenotypes (extent of disease, need of surgery, age of onset, extra-intestinal manifestations and primary sclerosing cholangitis (PSC)) were conducted. The combination of 133 UC loci yielded good UC risk predictability (area under the curve [AUC] of 0.86). A higher cumulative allele score predicted higher UC risk. Through LR, several lines of evidence for genetic interactions were identified and successfully replicated in the WTCCC cohort. The genetic interactions combined with the gene-smoking interaction significantly improved predictability in the model (AUC, from 0.86 to 0.89, P=3.26E-05). Explained UC variance increased from 37% to 42% after adding the interaction terms. A within case analysis found suggested genetic association with PSC. Our study demonstrates that the LR methodology allows the identification and replication of high order genetic interactions in UC GWAS datasets. UC risk can be predicted by a 133 loci and improved by adding gene-gene and gene-environment interactions. PMID:24241240

Specific immunotherapy ameliorates ulcerative colitis.

PubMed

Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

2016-01-01

Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

Subcorneal pustular dermatosis and episcleritis associated with poorly controlled ulcerative colitis.

PubMed

Wargo, Jeffrey J; Adams, Megan; Trevino, Julian

2017-01-30

A man aged 56 years with a history of ulcerative colitis (UC) status postsubtotal colectomy was hospitalised with fevers, dry cough, eye redness and a new bloody, mucoid rectal discharge. 2 months prior to admission, the dermatologist had started him on dapsone for subcorneal pustular dermatosis but did not recognise that he had recently self-discontinued mesalamine enemas, inducing a flare of his UC. After a thorough inpatient evaluation, including flexible sigmoidoscopy, active UC involving the rectal stump was determined to be driving his dermatological and ophthalmological findings. By reinstituting mesalamine enemas, control of his UC was achieved and the extraintestinal manifestations of his inflammatory bowel disease (IBD) resolved. This case illustrates the importance of careful history taking and of early recognition of extraintestinal manifestations of IBD in order to appropriately target treatment and prevent unnecessary morbidity. 2017 BMJ Publishing Group Ltd.

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

PubMed

Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

2015-10-01

Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

PubMed Central

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena YZ; Martin, Patrick

2016-01-01

Background Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). Aim To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Methods Participants (5–17 years of age; 18–82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Results Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Conclusion Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844. PMID:26893546

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

PubMed

Ghione, Silvia; Sarter, Hélène; Fumery, Mathurin; Armengol-Debeir, Laura; Savoye, Guillaume; Ley, Delphine; Spyckerelle, Claire; Pariente, Benjamin; Peyrin-Biroulet, Laurent; Turck, Dominique; Gower-Rousseau, Corinne

2018-02-01

Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10 5 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/10 5 (+126%; P<0.001) and for UC, from 1.6 to 4.1/10 5 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Curcumin for maintenance of remission in ulcerative colitis.

PubMed

Kumar, Sushil; Ahuja, Vineet; Sankar, Mari Jeeva; Kumar, Atul; Moss, Alan C

2012-10-17

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon characterized by episodes of disease activity and symptom-free remission.There is paucity of evidence regarding the efficacy and safety of complementary or alternative medicines for the management of UC. Curcumin, an anti-inflammatory agent, has been used in many chronic inflammatory conditions such as rheumatoid arthritis, esophagitis and post-surgical inflammation. The efficacy of this agent for maintenance of remission in patients with UC has not been systematically evaluated. The primary objective was to systematically review the efficacy and safety of curcumin for maintenance of remission in UC. A computer-assisted literature search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed on July 11, 2012 to identify relevant publications. Proceedings from major gastroenterology meetings and references from published articles were also searched to identify additional studies. Randomized placebo-controlled trials (RCT) of curcumin for maintenance of remission in UC were included. Studies included patients (of any age) who were in remission at the time of recruitment. Co-interventions were allowed. Two authors independently extracted data and assessed the methodological quality of the included studies using the Cochrane risk of bias tool. Data were analyzed using Review Manager (RevMan 5.1). We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each dichotomous outcome. For continuous outcomes we calculated the mean difference (MD) and 95% CI. Only one trial (89 patients) fulfilled the inclusion criteria. This trial randomized 45 patients to curcumin and 44 patients to placebo. All patients received treatment with sulfasalazine or mesalamine. The study was rated as low risk of bias. Curcumin was administered orally in a dose of 2 g/day for six months. Fewer patients relapsed in the curcumin group than the placebo group at six months. Four per cent of patients in the curcumin group relapsed at six months compared to 18% of patients in the placebo group (RR 0.24, 95% CI 0.05 to 1.09; P = 0.06). There was no statistically significant difference in relapse rates at 12 months. Twenty-two per cent of curcumin patients relapsed at 12 months compared to 32% of placebo patients (RR 0.70, 95% CI 0.35 to 1.40; P = 0.31). A total of nine adverse events were reported in seven patients. These adverse events included sensation of abdominal bulging, nausea, transient hypertension, and transient increase in the number of stools. The authors did not report which treatment group the patients who experienced adverse events belonged to. The clinical activity index (CAI) at six months was significantly lower in the curcumin group compared to the placebo group (1.0 + 2.0 versus 2.2 + 2.3; MD -1.20, 95% CI -2.14 to -0.26). The endoscopic index (EI) at six months was significantly lower in the curcumin group than in the placebo group (0.8 + 0.6 versus 1.6 + 1.6; MD -0.80, 95% CI -1.33 to -0.27). Curcumin may be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine. However, further research in the form of a large scale methodologically rigorous randomized controlled trial is needed to confirm any possible benefit of curcumin in quiescent UC.

Comparative Evaluation between Sulfasalazine Alone and in Combination with Herbal Medicine on DSS-Induced Ulcerative Colitis Mice

PubMed Central

Shin, Mi-Rae; Kim, Kyeong Jo; Kim, Soo Hyun; Kim, Su Ji

2017-01-01

The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and sulfasalazine in combination with herbal medicine on dextran sodium sulfate- (DSS-) induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (n = 9): Group I (normal group), Group II (DSS control group), Group III (DSS + sulfasalazine (30 mg/kg)), Group IV (DSS + sulfasalazine (60 mg/kg)), and Group V (DSS + sulfasalazine (30 mg/kg) + Cinnamomi Cortex and Bupleuri Radix mixture (30 mg/kg) (SCB)). Colonic pathological changes were analyzed using hematoxyline/eosin staining. The antioxidant, inflammatory, and apoptotic protein levels were determined using western blotting. SCB supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SCB treatment significantly reduced the expression of proinflammatory signaling molecules through suppression of both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and prevented the apoptosis of the colon. Moreover, SCB administration significantly led to the upregulation of antioxidant enzymes including SOD and catalase. Taken together, SCB treatment might offer a better treatment for human UC than sulfasalazine alone or may be useful as an alternative therapeutic strategy against UC, without any evidence of side effects. PMID:29018816

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson’s Disease: A Pilot Randomized Controlled Trial

PubMed Central

Vergara-Diaz, Gloria; Osypiuk, Kamila; Hausdorff, Jeffrey M; Bonato, Paolo; Gow, Brian J; Miranda, Jose GV; Sudarsky, Lewis R; Tarsy, Daniel; Fox, Michael D; Gardiner, Paula; Thomas, Cathi A; Macklin, Eric A; Wayne, Peter M

2018-01-01

Objectives To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson’s disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Design Two-arm, wait-list controlled RCT. Settings Tertiary care hospital. Subjects Thirty-two subjects aged 40–75 diagnosed with idiopathic PD within 10 years. Interventions Six-month TC intervention added to usual care (UC) versus UC alone. Outcome Measures Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson’s Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Results Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [−0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conclusions Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

To evaluate the effectiveness of health care ethics consultation based on the goals of health care ethics consultation: a prospective cohort study with randomization.

PubMed

Chen, Yen-Yuan; Chu, Tzong-Shinn; Kao, Yu-Hui; Tsai, Pi-Ru; Huang, Tien-Shang; Ko, Wen-Je

2014-01-03

The growing prevalence of health care ethics consultation (HCEC) services in the U.S. has been accompanied by an increase in calls for accountability and quality assurance, and for the debates surrounding why and how HCEC is evaluated. The objective of this study was to evaluate the effectiveness of HCEC as indicated by several novel outcome measurements in East Asian medical encounters. Patients with medical uncertainty or conflict regarding value-laden issues, and requests made by the attending physicians or nurses for HCEC from December 1, 2009 to April 30, 2012 were randomly assigned to the usual care group (UC group) and the intervention group (HCEC group). The patients in the HCEC group received HCEC conducted by an individual ethics consultant. Data analysis was based on the intention-to-treat principle. Mann-Whitney test and Chi-squared test were used depending on the scale of measurement. Thirty-three patients (53.23%) were randomly assigned to the HCEC group and 29 patients were randomly assigned to the UC group. Among the 33 patients in the HCEC group, two (6.06%) of them ultimately did not receive a HCEC service. Among the 29 patients in the UC group, four (13.79%) of them received a HCEC service. The survival rate at hospital discharge did not differ between the two groups. Patients in the HCEC group showed significant reductions in the entire ICU stay and entire hospital stay. HCEC significantly facilitated achieving the goal of medical care (p < .01). Furthermore, patients in the HCEC group had a shorter ICU stay and shorter hospital stay after the occurrence of medical uncertainty or conflict regarding value-laden issues than those in the UC group. Our findings demonstrated that HCEC were associated with reduced consumption of medical resources as indicated by shorter entire ICU stay, entire hospital stay, and shorter ICU and hospital stay after the occurrence of the medical uncertainty or conflict regarding value-laden issues. This study also showed that HCEC facilitated achieving a consensus regarding the goal of medical care, which conforms to the goal of HCEC.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

PubMed

Domènech, Eugeni; Panés, Julián; Hinojosa, Joaquín; Annese, Vito; Magro, Fernando; Sturniolo, Giacomo Carlo; Bossa, Fabrizio; Fernández, Francisco; González-Conde, Benito; García-Sánchez, Valle; Dignass, Axel; Herrera, José Manuel; Cabriada, José Luis; Guardiola, Jordi; Vecchi, Maurizio; Portela, Francisco; Ginard, Daniel

2018-05-25

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

PubMed Central

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-01-01

Background/Aims To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Methods Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. Results This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). Conclusions ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA. PMID:26780088

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials.

PubMed

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-03-01

To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

Inpatient care expenditure of the elderly with chronic diseases who use public health insurance: Disparity in their last year of life.

PubMed

Chandoevwit, Worawan; Phatchana, Phasith

2018-06-01

The Thai elderly are eligible for the Civil Servant Medical Benefit Scheme (CS) or Universal Coverage Scheme (UCS) depending on their pre-retirement or their children work status. This study aimed to investigate the disparity in inpatient care expenditures in the last year of life among Thai elderly individuals who used the two public health insurance schemes. Using death registration and inpatient administrative data from 2007 to 2011, our subpopulation group included the elderly with four chronic disease groups: diabetes mellitus, hypertension and cardiovascular disease, heart disease, and cancer. Among 1,242,150 elderly decedents, about 40% of them had at least one of the four chronic disease conditions and were hospitalized in their last year of life. The results showed that the means of inpatient care expenditures in the last year of life paid by CS and UCS per decedent were 99,672 Thai Baht and 52,472 Thai Baht, respectively. On average, UCS used higher healthcare resources by diagnosis-related group relative weight measure per decedent compared with CS. In all cases, the rates of payment for inpatient treatment per diagnosis-related group adjusted relative weight were higher for CS than UCS. This study found that the disparities in inpatient care expenditures in the last year of life stemmed mainly from the difference in payment rates. To mitigate this disparity, unified payment rates for various types of treatment that reflect costs of hospital care across insurance schemes were recommended. Copyright © 2018 Elsevier Ltd. All rights reserved.

Motivational counselling for physical activity in patients with coronary artery disease not participating in cardiac rehabilitation.

PubMed

Reid, Robert D; Morrin, Louise I; Higginson, Lyall A J; Wielgosz, Andreas; Blanchard, Chris; Beaton, Louise J; Nelson, Chantal; McDonnell, Lisa; Oldridge, Neil; Wells, George A; Pipe, Andrew L

2012-04-01

Many patients with coronary artery disease (CAD) fail to attend cardiac rehabilitation following acute coronary events because they lack motivation to exercise. Theory-based approaches to promote physical activity among non-participants in cardiac rehabilitation are required. A randomized trial comparing physical activity levels at baseline, 6, and 12 months between a motivational counselling (MC) intervention group and a usual care (UC) control group. One hundred and forty-one participants hospitalized with acute coronary syndromes not planning to attend cardiac rehabilitation were recruited at a single centre and randomized to either MC (n = 69) or UC (n = 72). The MC intervention, designed from an ecological perspective, included one face-to-face contact and eight telephone contacts with a trained physiotherapist over a 52-week period. The UC group received written information about starting a walking programme and brief physical activity advice from their attending cardiologist. Physical activity was measured by: 7-day physical activity recall interview; self-report questionnaire; and pedometer at baseline, 6, and 12 months after randomization. Latent growth curve analyses, which combined all three outcome measures into a single latent construct, showed that physical activity increased more over time in the MC versus the UC group (µ(add) = 0.69, p < 0.05). Patients with CAD not participating in cardiac rehabilitation receiving a theory-based motivational counselling intervention were more physically active at follow-up than those receiving usual care. This intervention may extend the reach of cardiac rehabilitation by increasing physical activity in those disinclined to participate in structured programmes.

[Cardiovascular risk reduction: impact of an international project].

PubMed

Colle, B; Brusaferro, S

2008-01-01

The Euroaction project, promoted by European Society of Cardiology, aims to determine whether a nurse co-ordinated, multidisciplinary, family based preventive cardiology programme could help more patients and their families achieve the recommended European lifestyle, risk factor and therapeutic goals for cardiovascular disease prevention. EUROACTION was evaluated in a paired cluster randomized controlled trial, and the primary care branch included 6 European countries. Consecutive patients > 50 years and < 80 years, with no history of cardiovascular disease, were prospectively identified by the general practitioners with one of the following: (i) high total cardiovascular risk (HeartScore > or = 5% over 10 years, either now or when projected to age 60 years) and on no medical treatment for blood pressure, lipids or diabetes; (ii) on treatment with anti-hypertensive and/or lipid-lowering drug therapies started in the last year but with no diabetes; (iii) diagnosed with diabetes mellitus (treated by diet alone or with oral hypoglycaemic drug therapy and/or insulin) within the last three years in both intervention and usual care practices. All eligible high risk individuals and their partners were then invited by the nurse for an assessment of their lifestyle, risk factors and therapeutic management as soon as possible after identification. In the primary care intervention branch 1019 patients have been enrolled with no differences by sex and mean age 62, while in the control branch 1005 patients were recruited with mean age 63, female were 43%. The main results show that Intervention group (I) had a statistically significant improvement compared to Usual Care (UC) in the assumption of recommended quantity of fruit and vegetables (78.4% I vs 38.8% UC p=0.005), in the weight loss (weight loss > al 5% in subjects with BMI > 25 kg/m2) (16.5% I vs 6.8% UC p=0.005), in blood pressure control both in people specifically treated with drugs and untreated (respectively 52% I vs 35% UC p=0.04 and 65% Ivs 45% UC p=0.02), in reaching the European target for total cholesterol (Total Cholesterol < 5.0 mmol/l) during the study year (from 21.9% to 35.8% (I) absolute increase 12.7% (p=0.025) vs from 33% to 32.2% (UC)). No significant differences were found about change of smoking habits. The experimented intervention model based on a multidisciplinary approach and nurses leaded showed a good one year impact in reducing cardiovascular risk factors in high risk people. This model should be further tested in local contexts.

Differentiation-dependent rearrangements of actin filaments and microtubules hinder apical endocytosis in urothelial cells.

PubMed

Tratnjek, Larisa; Romih, Rok; Kreft, Mateja Erdani

2017-08-01

During differentiation, superficial urothelial cells (UCs) of the urinary bladder form the apical surface, which is almost entirely covered by urothelial plaques containing densely packed uroplakin particles. These urothelial plaques are the main structural components of the blood-urine permeability barrier in the urinary bladder. We have shown previously that endocytosis from the apical plasma membrane decreases during urothelial cell differentiation. Here, we investigated the role of actin filament and microtubule rearrangements in apical endocytosis of differentiating UCs cells using hyperplastic and normoplastic porcine urothelial models. Partially differentiated normal porcine UCs contained actin filaments in the subapical cytoplasm, while microtubules had a net-like appearance. In highly differentiated UCs, actin filaments mostly disappeared from the subapical cytoplasm and microtubules remained as a thin layer close to the apical plasma membrane. Inhibition of actin filament formation with cytochalasin-D in partially differentiated UCs caused a decrease in apical endocytosis. Depolymerisation of microtubules with nocodazole did not prevent endocytosis of the endocytotic marker WGA into the subapical cytoplasm; however, it abolished WGA transport to endolysosomal compartments in the central cytoplasm. Cytochalasin-D or nocodazole treatment did not significantly change apical endocytosis in highly differentiated UCs. In conclusion, we showed that the physiological differentiation-dependent or chemically induced redistribution and reorganization of actin filaments and microtubules impair apical endocytosis in UCs. Importantly, reduced apical endocytosis due to cytoskeletal rearrangements in highly differentiated UCs, together with the formation of rigid urothelial plaques, reinforces the barrier function of the urothelium.

Biological and clinical implications of herbal medicine and natural products for the treatment of inflammatory bowel disease.

PubMed

Guo, Bao-Jian; Bian, Zhao-Xiang; Qiu, Hong-Cong; Wang, Yi-Tao; Wang, Ying

2017-08-01

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that includes Crohn's disease (CD) and ulcerative colitis (UC). Homeostasis of various regulatory factors involved with intestinal immunity is disrupted in IBD, including the intestinal epithelial barrier, macrophages, and cellular mediators such as cytokines and chemokines. No successful treatment is currently available for the management of IBD. Natural products and herbal medicines have exhibited efficacy for UC and CD in experimental models and clinical trials with the following activities: (1) maintenance of integrity of the intestinal epithelial barrier, (2) regulation of macrophage activation, (3) modulation of innate and adaptive immune response, and (4) inhibition of TNF-α activity. Here, we discuss the major factors involved in the pathogenesis of IBD and the current development of natural products and herbs for the treatment of IBD. © 2017 New York Academy of Sciences.

CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis

PubMed Central

Zhao, Jia-Jun; Wang, Di; Yao, Hui; Sun, Da-Wei; Li, Hong-Yu

2015-01-01

AIM: To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran’s Q-statistic and I2 tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger’s linear regression test were inspected for indication of publication bias. RESULTS: A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222-1.886, P < 0.001). CONCLUSION: CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk. PMID:26379408

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology.

PubMed

Zhang, Bei-Ying; Wang, Bing-Yun; Li, Shao-Chuan; Luo, Dong-Zhang; Zhan, Xiaoshu; Chen, Sheng-Feng; Chen, Zhi-Sheng; Liu, Can-Ying; Ji, Hui-Qin; Bai, Yin-Shan; Li, Dong-Sheng; He, Yang

2018-01-01

The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro . A suspension of allogeneic UC-MSCs (1 × 10 6 ) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF- α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF- α of the untreated control group were significantly higher than those of the treated group ( P < 0.05) 7-14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference ( P < 0.01). Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response.

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology

PubMed Central

Zhang, Bei-ying; Li, Shao-chuan; Luo, Dong-zhang; Zhan, Xiaoshu; Chen, Sheng-feng; Chen, Zhi-sheng; Liu, Can-ying; Ji, Hui-qin; Bai, Yin-shan; Li, Dong-sheng; He, Yang

2018-01-01

Objective The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Methods Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro. A suspension of allogeneic UC-MSCs (1 × 106) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF-α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF-α of the untreated control group were significantly higher than those of the treated group (P < 0.05) 7–14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference (P < 0.01). Conclusion Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response. PMID:29861739

LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.

PubMed

Chen, Ting; Gu, Chengxin; Xue, Cailin; Yang, Tao; Zhong, Yun; Liu, Shiming; Nie, Yuqiang; Yang, Hui

2017-01-01

Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.

Systematic analysis of annual health resource utilization and costs in hospitalized patients with inflammatory bowel disease in Switzerland.

PubMed

Schoepfer, Alain; Vavricka, Stephan R; Brüngger, Beat; Reich, Oliver; Blozik, Eva; Bähler, Caroline

2018-05-11

Real-life data on health resource utilization and costs of hospitalized patients with inflammatory bowel disease are lacking in Switzerland. We aimed to assess health resource utilization and costs during a 1-year follow-up period starting with an index hospitalization. On the basis of claims data of the Helsana health insurance group, health resource utilization was assessed and costs reimbursed by mandatory basic health insurance [in Swiss Francs (CHF); 1 CHF=0.991 US$] were calculated during a 1-year follow-up period starting with an index hospitalization in the time period between 1 January 2013 and 31 December 2014. Of 202 002 patients with at least one hospitalization in 2013-2014, a total of 270 (0.13%) patients had inflammatory bowel disease as main diagnosis [112 (41.5%) ulcerative colitis (UC), 158 (58.5%) Crohn's disease (CD), 154/270 (57.0%) females]. In comparison with patients with UC, patients with CD were significantly more frequently treated with biologics (45.6 vs. 20.5%, P<0.001) and more frequently underwent surgery during index hospitalization (27.8 vs. 9.8%, P=0.002). Compared with patients with UC, those with CD had significantly more consultations [odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01-1.12, P=0.016], higher median annual total costs (OR: 1.25, 95% CI: 1.05-1.48, P=0.012), and higher outpatient costs (OR: 1.33, 95% CI: 1.07-1.66, P=0.011). In the bivariate model, median total costs for patients with CD and those with UC were 24 270 and 17 270 CHF, respectively (P=0.032). When compared with patients with UC, hospitalized patients with CD have during a 1-year follow-up a higher rate of outpatient consultations and generate higher costs.

Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis.

PubMed

Vieira de Barros, Karina; Gomes de Abreu, Gilclay; Xavier, Roberta Araujo Navarro; Real Martinez, Carlos Augusto; Ribeiro, Marcelo Lima; Gambero, Alessandra; de Oliveira Carvalho, Patrícia; Silveira, Vera Lúcia Flor

2011-02-01

High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. Copyright © 2011 Elsevier Inc. All rights reserved.

The estimation of uniaxial compressive strength conversion factor of trona and interbeds from point load tests and numerical modeling

NASA Astrophysics Data System (ADS)

Ozturk, H.; Altinpinar, M.

2017-07-01

The point load (PL) test is generally used for estimation of uniaxial compressive strength (UCS) of rocks because of its economic advantages and simplicity in testing. If the PL index of a specimen is known, the UCS can be estimated using conversion factors. Several conversion factors have been proposed by various researchers and they are dependent upon the rock type. In the literature, conversion factors on different sedimentary, igneous and metamorphic rocks can be found, but no study exists on trona. In this study, laboratory UCS and field PL tests were carried out on trona and interbeds of volcano-sedimentary rocks. Based on these tests, PL to UCS conversion factors of trona and interbeds are proposed. The tests were modeled numerically using a distinct element method (DEM) software, particle flow code (PFC), in an attempt to guide researchers having various types of modeling problems (excavation, cavern design, hydraulic fracturing, etc.) of the abovementioned rock types. Average PFC parallel bond contact model micro properties for the trona and interbeds were determined within this study so that future researchers can use them to avoid the rigorous PFC calibration procedure. It was observed that PFC overestimates the tensile strength of the rocks by a factor that ranges from 22 to 106.

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia.

PubMed

Lazarevic, Vladimir; Hörstedt, Ann-Sofi; Johansson, Bertil; Antunovic, Petar; Billström, Rolf; Derolf, Åsa; Lehmann, Sören; Möllgård, Lars; Peterson, Stefan; Stockelberg, Dick; Uggla, Bertil; Vennström, Lovisa; Wahlin, Anders; Höglund, Martin; Juliusson, Gunnar

2015-05-01

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dietary protein intakes and risk of ulcerative colitis.

PubMed

Rashvand, Samaneh; Somi, Mohammad Hossein; Rashidkhani, Bahram; Hekmatdoost, Azita

2015-01-01

The incidence of ulcerative colitis (UC) is rising in populations with western-style diet, rich in fat and protein, and low in fruits and vegetables. In the present study, we aimed to evaluate the association between dietary protein intakes and the risk of developing incident UC. Sixty two cases of UC and 124 controls were studied using country-specific food frequency questionnaire (FFQ). Group comparisons by each factor were done using χ2 test, and significance level was set at α= 0.05. Logistic regression adjusted for potential confounding variables was carried out. Univariate analysis suggested positive associations between processed meat, red meat and organ meat with risk of ulcerative colitis. Comparing highest versus lowest categories of consumption, multivariate conditional logistic regression analysis accounting for potential confounding variables indicated that patients who consumed a higher amount of processed meat were at a higher risk for developing UC (P value for trend= 0.02). Similarly, patients who consumed higher amounts of red meat were at a higher risk for UC (P value for trend= 0.01). The highest tertile of intake of organ meat was associated with an increased risk of ulcerative colitis with a statistically significant trend across tertiles (P value for trend= 0.01) when adjusted. In this case-control study we observed that higher consumptions of processed meat, red meat and organ meat were associated with increased risk for UC.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

A case-control study on the risk factors of urinary calculus in Uyghur children in the Kashi region.

PubMed

Wang, H C; Liu, C; He, H Y; Wang, M X

2015-06-01

The incidence of urinary calculus (UC) is very high in Uyghur children in the Kashi region of Xinjiang, China, which seriously affects the growth and life quality of these children. This study was aimed at investigating the risk factors of UC in Uyghur children in Kashi region. One hundred fifteen Uyghur children (age <7 years) with UC who were treated in First People's Hospital in Kashi were enrolled in the case group. A 1:1 case-control study with a questionnaire was performed. The results showed that, among the 115 UC patients, there were more boys (71.3%) than girls (28.7%), and most cases had an onset age of 1-3 years (75.7%). A lower than primary school education in the mother, drinking unboiled water, water intake <500 mL/day, and eating too much sweets were risk factors [odds ratio (OR) = 2.385, 9.160, 3.263, and 8.945, respectively], whereas vegetable intake and exposure to summer sunshine of <2 h/day were protective factors against UC onset (OR = 0.154 and 0.344, respectively). Analysis of UC-related factors in 99 cases of <3-year-old children revealed that breastfeeding was also a protective factor (OR = 0.007), whereas frequent cow's milk intake within 5 months (OR = 2.414) and frequent "panada" intake (OR = 2.529) were risk factors. The occurrence of UC in Uyghur children in the Kashi region is mainly affected by maternal educational background, quality of drinking water, water intake volume, and dietary pattern. Furthermore, geography may also have a role.

Mass Spectrometry Data Set for Renal Cell Carcinoma and Polycystic Kidney Disease Cell Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, B. J.

This data set will be evaluated by collaborators at UC Davis for possible inclusion in a research paper for publication in a scientific journal and to assist in the design of additional experiments. Researchers from UC Davis and LLNL will contribute to the manuscript.

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

PubMed Central

Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

2015-01-01

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis.

PubMed

Mortensen, Joachim Høg; Godskesen, Line Elbjerg; Jensen, Michael Dam; Van Haaften, Wouter Tobias; Klinge, Lone Gabriels; Olinga, Peter; Dijkstra, Gerard; Kjeldsen, Jens; Karsdal, Morten Asser; Bay-Jensen, Anne-Christine; Krag, Aleksander

2015-10-01

A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD. Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers. All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively. Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study.

PubMed

Kopylov, Uri; Papamichael, Konstantinos; Katsanos, Konstantinos; Waterman, Matti; Bar-Gil Shitrit, Ariella; Boysen, Trine; Portela, Francisco; Peixoto, Armando; Szilagyi, Andrew; Silva, Marco; Maconi, Giovanni; Har-Noy, Ofir; Bossuyt, Peter; Mantzaris, Gerassimos; Barreiro de Acosta, Manuel; Chaparro, Maria; Christodoulou, Dimitrios K; Eliakim, Rami; Rahier, Jean-Francois; Magro, Fernando; Drobne, David; Ferrante, Marc; Sonnenberg, Elena; Siegmund, Britte; Muls, Vinciane; Thurm, Tamara; Yanai, Henit; Dotan, Iris; Raine, Tim; Levin, Avi; Israeli, Eran; Ghalim, Fahd; Carbonnel, Franck; Vermeire, Severine; Ben-Horin, Shomron; Roblin, Xavier

2017-09-01

Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Treating Anxiety Disorders in Inner City Schools: Results from a Pilot Randomized Controlled Trial Comparing CBT and Usual Care

PubMed Central

Becker, Kimberly D.; Drazdowski, Tess K.; Tein, Jenn-Yun

2012-01-01

Background The effectiveness of cognitive-behavioral treatment (CBT) in inner city schools, when delivered by novice CBT clinicians, and compared to usual care (UC), is unknown. Objective This pilot study addressed this issue by comparing a modular CBT for anxiety disorders to UC in a sample of 32 volunteer youth (mean age 10.28 years, 63% female, 84% African American) seen in school-based mental health programs. Methods Youth were randomly assigned to CBT (n = 17) or UC (n = 15); independent evaluators conducted diagnostic interviews with children and parents at pre- and post-intervention, and at a one-month follow-up. Results Based on intent-to-treat analyses, no differences were found in response rates between groups with 50 and 42% of the children in CBT, compared to 46 and 57% in UC no longer meeting criteria for an anxiety disorder at post-treatment and follow-up respectively. Similar improvements in global functioning were also found in both treatment groups. Baseline predictors of a positive treatment response included lower anxiety, fewer maladaptive thoughts, less exposure to urban hassles, and lower levels of parenting stress. Therapist use of more CBT session structure elements and greater competence in implementing these elements was also related to a positive treatment response. Conclusions Findings from this small pilot failed to show that CBT was superior to UC when delivered by school-based clinicians. Large scale comparative effectiveness trials are needed to determine whether CBT leads to superior clinical outcomes prior to dissemination. PMID:22701295

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

PubMed

Costello, S P; Soo, W; Bryant, R V; Jairath, V; Hart, A L; Andrews, J M

2017-08-01

Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. To determine whether FMT is effective and safe for the induction of remission in active UC. Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent. © 2017 John Wiley & Sons Ltd.

Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis.

PubMed

Polychronopoulou, Erietta; Lygoura, Vasiliki; Gatselis, Nikolaos K; Dalekos, George N

2017-09-25

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients.

PubMed

Kumsiri, Ratchanok; Troye-Blomberg, Marita; Pattanapanyasat, Kovit; Krudsood, Srivicha; Maneerat, Yaowapa

2016-02-01

Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-α and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-α levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p=0.011) and S groups (p=0.025) were significantly higher than those in C group. In contrast the TNF-α levels tended to be higher in the UC than those in the S (p=0.343) and significantly higher than those in C (p=0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p<0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r=-0.762, p=0.028), and TNF-α and IgE-IgG complexes (r=-0.715, p=0.002). Significant positive correlations between levels of specific IgE and TNF-α (r=0.575, p=0.010); and sCD23 (r=0.597, p=0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-α and the malaria-specific IgG may correlate with protection against falciparum malaria. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Mesenchymal Stem Cells from Human Amniotic Membrane and Umbilical Cord Can Diminish Immunological Response in an in vitro Allograft Model.

PubMed

Dabrowski, Filip A; Burdzinska, Anna; Kulesza, Agnieszka; Chlebus, Marcin; Kaleta, Beata; Borysowski, Jan; Zolocinska, Aleksandra; Paczek, Leszek; Wielgos, Miroslaw

2017-01-01

Mesenchymal stem cells (MSCs) are gaining rising interest in gynecology and obstetrics. MSCs immunomodulatory properties are suitable enough to reduce perinatal morbidity caused by inflammation in premature neonates. The aim of this study was to evaluate and compare the ability to inhibit allo-activated lymphocytes proliferation by MSCs derived from different sources: amniotic membrane (AM), umbilical cord (UC) and adipose tissue (AT). MSCs were isolated from AM (n = 7) and UC (n = 6) and AT (n = 6) of healthy women. Cells were characterized by flow cytometry and differentiation assay. To evaluate the potential of fetal and adult MSCs to diminish immunological response, mixed lymphocytes reaction (MLR) was performed. Amnion and UC-derived cells displayed typical MSCs characteristics. Addition of MSCs to MLR significantly inhibited the proliferation of stimulated lymphocytes. The effect was observed regardless of the MSCs type used (p < 0.01 in all groups). Comparative analysis revealed no significant differences in this action between tested MSCs types. Additionally, no type of MSCs significantly stimulated allogeneic lymphocytes. The results prove the immunosuppressive capacities of fetal-derived MSCs in vitro. In the future, they may be potentially used to treat premature newborn as well as in immunomodulation in post-transplant therapy. © 2016 S. Karger AG, Basel.

[Ursolic acid inhibits corneal graft rejection following orthotopic allograft transplantation in rats].

PubMed

Wang, Bo; Wu, Jing; Ma, Ming; Li, Ping-Ping; Yu, Jian

2015-04-01

To investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation. Forty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). The allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found. As a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.

Aberrant excitatory rewiring of layer V pyramidal neurons early after neocortical trauma

PubMed Central

Takahashi, D. Koji; Isabel, Feng Gu; Parada, Shri Vyas; Prince, David A.

2016-01-01

Lesioned neuronal circuits form new functional connections after a traumatic brain injury (TBI). In humans and animal models, aberrant excitatory connections that form after TBI may contribute to the pathogenesis of post-traumatic epilepsy. Partial neocortical isolation (“undercut” or “UC”) leads to altered neuronal circuitry and network hyperexcitability recorded in vivo and in brain slices from chronically lesioned neocortex. Recent data suggest a critical period for maladaptive excitatory circuit formation within the first 3 days post UC injury (Graber and Prince, 1999, 2004; Li et al., 2011, 2012b). The present study focuses on alterations in excitatory connectivity within this critical period. Immunoreactivity (IR) for growth-associated protein (GAP)-43 was increased in the UC cortex 3 days after injury. Some GAP-43-expressing excitatory terminals targeted the somata of layer V pyramidal (Pyr) neurons, a domain usually innervated predominantly by inhibitory terminals. Immunocytochemical analysis of pre- and postsynaptic markers showed that putative excitatory synapses were present on somata of these neurons in UC neocortex. Excitatory postsynaptic currents from UC layer V Pyr cells displayed properties consistent with perisomatic inputs and also reflected an increase in the number of synaptic contacts. Laser scanning photostimulation (LSPS) experiments demonstrated reorganized excitatory connectivity after injury within the UC. Concurrent with these changes, spontaneous epileptiform bursts developed in UC slices. Results suggest that aberrant reorganization of excitatory connectivity contributes to early neocortical hyperexcitability in this model. The findings are relevant for understanding the pathophysiology of neocortical post-traumatic epileptogenesis and are important in terms of the timing of potential prophylactic treatments. PMID:26956396

The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease.

PubMed

Kim, Dong Uk; Kim, Young-Ho; Kim, Beom Jin; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul

2009-01-01

Azathioprine (AZA) and 6-mercaptopurine (6-MP) have been widely used in patients with ulcerative colitis (UC) and Crohn's disease (CD). However, some patients cannot tolerate standard doses (2-2.5 mg/kg for AZA or 1-1.5 mg/kg for 6-MP) due to side effects such as leukopenialneutropenia. The aim of this study was to evaluate the efficacy of low dose AZA/6-MP compared to the standard dose. From 1995 to 2005, 122 patients with UC or CD treated with AZA/6-MP at Samsung Medical Center in Korea were enrolled. We divided these patients into 2 groups (standard dose group versus low dose group) according to the maintenance dose. Among the 122 patients, 17 received the standard dose and 105 received a low dose. The mean maintenance doses were 2.25 mg/kg for the standard dose group and 1.35mg/kg for the low dose group. The clinical outcomes of remission induction, maintenance of remission and relapse rate showed no significant difference in comparisons between these two groups. Low dose AZA/6-MP was as effective as the standard dose for remission induction and maintenance of remission in patients with UC and CD. For patients that develop leukopenia/neutropenia during dose escalation, maintenance therapy with low dose AZA/6-MP should be considered.

A Randomized Controlled Trial of a Group Motivational Interviewing Intervention for Adolescents with a First Time Alcohol or Drug Offense

PubMed Central

D’Amico, Elizabeth J.; Hunter, Sarah B.; Miles, Jeremy N.V.; Ewing, Brett A.; Osilla, Karen Chan

2013-01-01

Group Motivational Interviewing (MI) interventions that target youth at-risk for alcohol and other drug (AOD) use may prevent future negative consequences. Youth in a teen court setting (n=193; 67% male, 45% Hispanic; mean age 16.6 (SD = 1.05) were randomized to receive either a group MI intervention, Free Talk, or usual care (UC). We examined client acceptance, intervention feasibility and conducted a preliminary outcome evaluation. Free Talk teens reported higher quality and satisfaction ratings, and MI integrity scores were higher for Free Talk groups. AOD use and delinquency decreased for both groups at three months, and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC. Results contribute to emerging literature on MI in a group setting. A longer term follow-up is warranted. PMID:23891459

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.

PubMed

Huang, Tzou-Chi; Tsai, Shinn-Shyong; Liu, Li-Fang; Liu, Yu Lin; Liu, Hung-Jen; Chuang, Kuo Pin

2010-09-07

To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in colonic sections were detected by immunohistochemistry. There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups. We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.

Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative Colitis: A Simulation Model.

PubMed

Scott, Frank I; Shah, Yash; Lasch, Karen; Luo, Michelle; Lewis, James D

2018-01-18

Vedolizumab, an α4β7 integrin monoclonal antibody inhibiting gut lymphocyte trafficking, is an effective treatment for ulcerative colitis (UC). We evaluated the optimal position of vedolizumab in the UC treatment paradigm. Using Markov modeling, we assessed multiple algorithms for the treatment of UC. The base case was a 35-year-old male with steroid-dependent moderately to severely active UC without previous immunomodulator or biologic use. The model included 4 different algorithms over 1 year, with vedolizumab use prior to: initiating azathioprine (Algorithm 1), combination therapy with infliximab and azathioprine (Algorithm 2), combination therapy with an alternative anti-tumor necrosis factor (anti-TNF) and azathioprine (Algorithm 3), and colectomy (Algorithm 4). Transition probabilities and quality-adjusted life-year (QALY) estimates were derived from the published literature. Primary analyses included simulating 100 trials of 100,000 individuals, assessing clinical outcomes, and QALYs. Sensitivity analyses employed longer time horizons and ranges for all variables. Algorithm 1 (vedolizumab use prior to all other therapies) was the preferred strategy, resulting in 8981 additional individuals in remission, 18 fewer cases of lymphoma, and 1087 fewer serious infections per 100,000 patients compared with last-line use (A4). Algorithm 1 also resulted in 0.0197 to 0.0205 more QALYs compared with other algorithms. This benefit increased with longer time horizons. Algorithm 1 was preferred in all sensitivity analyses. The model suggests that treatment algorithms positioning vedolizumab prior to other therapies should be considered for individuals with moderately to severely active steroid-dependent UC. Further prospective research is needed to confirm these simulated results. © 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis.

PubMed

Cheng, Yang; Zhu, Yun; Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn's disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted.

Cost-Effectiveness of a Technology-Facilitated Depression Care Management Adoption Model in Safety-Net Primary Care Patients with Type 2 Diabetes.

PubMed

Hay, Joel W; Lee, Pey-Jiuan; Jin, Haomiao; Guterman, Jeffrey J; Gross-Schulman, Sandra; Ell, Kathleen; Wu, Shinyi

2018-05-01

The Diabetes-Depression Care-Management Adoption Trial is a translational study of safety-net primary care predominantly Hispanic/Latino patients with type 2 diabetes in collaboration with the Los Angeles County Department of Health Services. To evaluate the cost-effectiveness of an information and communication technology (ICT)-facilitated depression care management program. Cost-effectiveness of the ICT-facilitated care (TC) delivery model was evaluated relative to a usual care (UC) and a supported care (SC) model. TC added automated low-intensity periodic depression assessment calls to patients. Patient-reported outcomes included the 12-Item Short Form Health Survey converted into quality-adjusted life-years (QALYs) and the 9-Item Patient Health Questionnaire-calculated depression-free days (DFDs). Costs and outcomes data were collected over a 24-month period (-6 to 0 months baseline, 0 to 18 months study intervention). A sample of 1406 patients (484 in UC, 480 in SC, and 442 in TC) was enrolled in the nonrandomized trial. TC had a significant improvement in DFDs (17.3; P = 0.011) and significantly greater 12-Item Short Form Health Survey utility improvement (2.1%; P = 0.031) compared with UC. Medical costs were statistically significantly lower for TC (-$2328; P = 0.001) relative to UC but not significantly lower than for SC. TC had more than a 50% probability of being cost-effective relative to SC at willingness-to-pay thresholds of more than $50,000/QALY. An ICT-facilitated depression care (TC) delivery model improved QALYs, DFDs, and medical costs. It was cost-effective compared with SC and dominant compared with UC. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

PubMed Central

Halling, Morten L; Kjeldsen, Jens; Knudsen, Torben; Nielsen, Jan; Hansen, Lars Koch

2017-01-01

AIM To investigate whether immune mediated diseases (IMD) are more frequent in patients with inflammatory bowel disease (IBD). METHODS In this population based registry study, a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16, 2013. Controls were randomly selected from the Danish Civil Registration System (CRS) and matched for sex, age, and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis (UC), Crohn’s disease (CD) and Both the latter referring to those registered with both diagnoses. Subsequently, odds-ratios (OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher’s exact test. RESULTS There were significantly more women than men in the registry, and a greater percentage of comorbidity in the IBD groups (P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased (P < 0.00125) for primary sclerosing cholangitis (PSC), celiac disease, type 1 diabetes (T1D), sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis. Restricted to UC (P < 0.00125) were autoimmune hepatitis, primary biliary cholangitis, Grave’s disease, polymyalgia rheumatica, temporal arteritis , and atrophic gastritis. Restricted to CD (P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC (P < 0.00125) were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica. Restricted to women with CD were episcleritis, rheumatoid arthritis, and psoriatic arthritis. The only disease restricted to men (P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways. PMID:28970729

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases.

PubMed

Halling, Morten L; Kjeldsen, Jens; Knudsen, Torben; Nielsen, Jan; Hansen, Lars Koch

2017-09-07

To investigate whether immune mediated diseases (IMD) are more frequent in patients with inflammatory bowel disease (IBD). In this population based registry study, a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16, 2013. Controls were randomly selected from the Danish Civil Registration System (CRS) and matched for sex, age, and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis (UC), Crohn's disease (CD) and Both the latter referring to those registered with both diagnoses. Subsequently, odds-ratios (OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P -values were estimated using Fisher's exact test. There were significantly more women than men in the registry, and a greater percentage of comorbidity in the IBD groups ( P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased ( P < 0.00125) for primary sclerosing cholangitis (PSC), celiac disease, type 1 diabetes (T1D), sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis. Restricted to UC ( P < 0.00125) were autoimmune hepatitis, primary biliary cholangitis, Grave's disease, polymyalgia rheumatica, temporal arteritis , and atrophic gastritis. Restricted to CD ( P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC ( P < 0.00125) were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica. Restricted to women with CD were episcleritis, rheumatoid arthritis, and psoriatic arthritis. The only disease restricted to men ( P < 0.00125) was sarcoidosis. Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Transurethral Resection of Bladder Tumors: Next-generation Virtual Reality Training for Surgeons.

PubMed

Neumann, Eva; Mayer, Julian; Russo, Giorgio Ivan; Amend, Bastian; Rausch, Steffen; Deininger, Susanne; Harland, Niklas; da Costa, Inês Anselmo; Hennenlotter, Jörg; Stenzl, Arnulf; Kruck, Stephan; Bedke, Jens

2018-05-22

The number of virtual reality (VR) simulators is increasing. The aim of this prospective trial was to determine the benefit of VR cystoscopy (UC) and transurethral bladder tumor resection (TURBT) training in students. Medical students without endoscopic experience (n=51, median age=25 yr, median 4th academic year) were prospectively randomized into groups A and B. After an initial VR-UC and VR-TURBT task, group A (n=25) underwent a video-based tutorial by a skilled expert. Group B (n=26) was trained using a VR training program (Uro-Trainer). Following the training, every participant performed a final VR-UC and VR-TURBT task. Performance indicators were recorded via the simulator. Data was analyzed by Mann-Whitney U test. VR cystoscopy and TURBT. No baseline and post-training differences were found for VR-UC between groups. During baseline, VR-TURBT group A showed higher inspected bladder surface than group B (56% vs 73%, p=0.03). Subgroup analysis detected differences related to sex before training (male: 31.2% decreased procedure time; 38.1% decreased resectoscope movement; p=0.02). After training, significant differences in procedure time (3.9min vs 2.7min, p=0.007), resectoscope movement (857mm vs 529mm, p=0.005), and accidental bladder injury (n=3.0 vs n=0.88, p=0.003) were found. Male participants showed reduced blood loss (males: 3.92ml vs females: 10.12ml; p=0.03) after training. Measuring endoscopic skills within a virtual environment can be done easily. Short training improved efficacy and safety of VR-TURBT. Nevertheless, transfer of improved VR performance into real world surgery needs further clarification. We investigated how students without endoscopic experience profit from simulation-based training. The safe environment and repeated simulations can improve the surgical training. It may be possible to enhance patient's safety and the training of surgeons in long term. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Protective effect of Averrhoa bilimbi L. fruit extract on ulcerative colitis in wistar rats via regulation of inflammatory mediators and cytokines.

PubMed

Suluvoy, Jagadish Kumar; Sakthivel, K M; Guruvayoorappan, C; Berlin Grace, V M

2017-07-01

Ulcerative Colitis (UC) is a lingering type of Inflammatory Bowel Disease (IBD) which affects the colon mucosa. Ulcerative colitis is majorly associated with oxidative stress and inflammation in colon tissue leading to damage. Averrhoa bilimbi L. fruit is rich in antioxidant phytochemicals including Vitamin C. In the current research, we have evaluated the defence mechanism of Averrhoa bilimbi L. on Ulcerative Colitis (UC). Male wistar rats were treated with Averrhoa bilimbi L. fruit extract (50mg/kg/bwt and 100mg/kg/bwt) and a standard drug Sulfasalazine (100mg/kg/bwt) for 6 consecutive days via intra peritoneally. After one day fasting, rats were given single dose of 3% 2ml of acetic acid through anal (intra-anal) region to induce Ulcerative Colitis. The protective and therapeutic effect of fruit extract on UC was assessed by comparing the relevant changes observed in the normal and treated group. In treated group the level of mucosal injury was decreased (ulcer score - 2) when compared to the control group (ulcer score - 9). The abnormal increase observed in the inflammation mediator cytokines in control rats, i.e IL-1β, IL-6, TNF-α levels were decreased significantly (**p<0.01) in the Averrhoa bilimbi L. fruit extract treated groups. The increase in weights of the colon tissue and spleen of the control rats were found to be reduced in treated groups. The levels of inflammatory markers iNOS and COX-2 were also decreased in treated group significantly (**p<0.01) when compared with the control. Furthermore, the treatment with Averrhoa bilimbi L. fruit extract has shown a significant antioxidant activity in the UC condition by reducing the levels of NO and enhancing the levels of SOD and GSH in the colon tissue. These results demonstrate the effective anti-ulcerative colitis activity of the Averrhoa bilimbi L. fruit extract in experimental wistar rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of skeletal maturity using maxillary canine, mandibular second and third molar calcification stages.

PubMed

Trakinienė, Giedrė; Smailienė, Dalia; Kučiauskienė, Ainė

2016-08-01

The objective of this study was to evaluate whether the calcification stages of maxillary canine, mandibular second molar, and mandibular third molar can be used for assessment of growth phase. The study group consisted of 274 subjects. Pre-treatment digital panoramic and lateral cephalometric radiographs of the patients were analysed. The patients' age was ranging from 7 to 19 years. Right maxillary canine, mandibular second molar and third molar were used as a sample. The teeth mineralization was assessed using modification of Gleiser and Hunt method. The skeletal maturation was assessed by the cervical vertebrae maturation (CVM) method. A significant association was found between CVM stage 2 and maxillary canine (UC) stage 4, mandibular second molar (LM2) stage 4, and mandibular third molar (LM3) stage 1. CVM stage 3 corresponded with UC stage 5, LM2 stage 5, LM3 stage 2. CVM stage 4 matched with UC stage 5, LM2 stage 6 and LM3 stage 3. The highest correlations between CVM and calcification stages were in the group of the maxillary canine (r = 0.812, P < 0.01) and mandibular second molar (r = 0.824, P < 0.01). Limitation of our study was that the study sample was not very big and the distribution value in the groups was very high, so it was impossible to check more statistical parameters. The calcification stages of UC, LM2, and LM3 as indicators of skeletal maturity could be clinically used with caution, until this method is verified with a larger sample group. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The Association Between CMV Viremia or Endoscopic Features and Histopathological Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis.

PubMed

Yang, Hong; Zhou, Weixun; Lv, Hong; Wu, Dongsheng; Feng, Yunlu; Shu, Huijun; Jin, Meng; Hu, Lingling; Wang, Qiang; Wu, Dong; Chen, Jie; Qian, Jiaming

2017-05-01

Cytomegalovirus (CMV) infection has been shown to be related to severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this study was to evaluate the endoscopic and pathological characteristics of CMV colitis in patients with UC and to assess the predictive value of the endoscopic and pathological features of CMV colitis. A total of 50 consecutive UC patients with CMV infection who were admitted to Peking Union Medical College Hospital from 2010 to 2015 were enrolled in this study. Twenty-five UC patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%, respectively. A higher proportion of endoscopic punched-out ulcers, irregular ulcers, and cobblestone-like appearance were observed among the patients in the CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%, 60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of CMV inclusion bodies per high-power field was significantly higher in those with punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of pathological inflammation was observed in the CMV colitis group than in the control group (68.0% versus 44.0%). Characteristic endoscopic features with punch-out ulcers and high CMV viremia load may be useful for predicting the presence of CMV colitis in histology. Punch-out ulcers were found to be associated with a higher number of inclusion bodies on histology, suggesting a role of targeted biopsy for endoscopist.

Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

PubMed Central

Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

2014-01-01

Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

Intestinal colonization with phylogenetic group B2 Escherichia coli related to inflammatory bowel disease: a systematic review and meta-analysis.

PubMed

Petersen, Andreas Munk; Halkjær, Sofie Ingdam; Gluud, Lise Lotte

2015-01-01

Increased numbers of Escherichia coli and, furthermore, specific subtypes of E. coli, such as E. coli of the phylogenetic groups B2 and D have been found in the intestine of patients with inflammatory bowel disease (IBD). In this review, we wanted to evaluate the relationship between B2 and D E. coli intestinal colonization and IBD. A systematic review with meta-analyses. We included studies comparing colonization with B2 and D E. coli in IBD patients and in controls. Random-effects and fixed-effect meta-analyses were performed. We included 7 studies on 163 patients with IBD and 89 controls. Among IBD patients, 57 patients had ulcerative colitis (UC) and 95 Crohn's disease (CD). Random-effects meta-analysis showed that IBD patients were more likely to have B2 E. coli intestinal colonization compared with controls (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.25-4.16). There was little between-study heterogeneity (I(2) = 0). The result was confirmed in subgroup analyses of patients with UC (OR: 3.58; 95% CI: 1.62-7.90), but not CD (OR: 1.94; 95% CI: 0.98-3.82). Intestinal colonization with phylogenetic group D E. coli was not found to be related to IBD, UC or CD. Our study reveals that intestinal colonization with phylogenetic group B2 E. coli is associated with UC. Due to the design, we are unable to determine if the colonization with B2 E. coli leads to the development of the disease or the disease increases the risk of colonization with B2 E. coli.

Biochemical and dietary factors of uric acid stone formation.

PubMed

Trinchieri, Alberto; Montanari, Emanuele

2018-04-01

The aim of this study was to compare the clinical characteristics of "pure" uric acid renal stone formers (UA-RSFs) with that of mixed uric acid/calcium oxalate stone formers (UC-RSFs) and to identify which urinary and dietary risk factors predispose to their formation. A total of 136 UA-RSFs and 115 UC-RSFs were extracted from our database of renal stone formers. A control group of 60 subjects without history of renal stones was considered for comparison. Data from serum chemistries, 24-h urine collections and 24-h dietary recalls were considered. UA-RSFs had a significantly (p = 0.001) higher body mass index (26.3 ± 3.6 kg/m 2 ) than UC-RSFs, whereas body mass index of UA-RSFs was higher but not significantly than in controls (24.6 ± 4.7) (p = 0.108). The mean urinary pH was significantly lower in UA-RSFs (5.57 ± 0.58) and UC-RSFs (5.71 ± 0.56) compared with controls (5.83 ± 0.29) (p = 0.007). No difference of daily urinary uric acid excretion was observed in the three groups (p = 0.902). Daily urinary calcium excretion was significantly (p = 0.018) higher in UC-RSFs (224 ± 149 mg/day) than UA-RSFs (179 ± 115) whereas no significant difference was observed with controls (181 ± 89). UA-RSFs tend to have a lower uric acid fractional excretion (0.083 ± 0.045% vs 0.107+/-0.165; p = 0.120) and had significantly higher serum uric acid (5.33 ± 1.66 vs 4.78 ± 1.44 mg/dl; p = 0.007) than UC-RSFs. The mean energy, carbohydrate and vitamin C intakes were higher in UA-SFs (1987 ± 683 kcal, 272 ± 91 g, 112 ± 72 mg) and UC-SFs (1836 ± 74 kcal, 265 ± 117, 140 ± 118) with respect to controls (1474 ± 601, 188 ± 84, 76 ± 53) (p = 0.000). UA-RSFs should be differentiated from UC-RSFs as they present lower urinary pH, lower uric acid fractional excretion and higher serum uric acid. On the contrary, patients with UC-RSFs show urinary risk factors more similar to those for calcium oxalate stones. The dietary approach in patients forming uric acid stones should be reconsidered with more attention to the quantity and quality of carbohydrate intake.

Prediction of mean circulation velocity in oxidation ditch.

PubMed

Simon, S; Roustan, M; Audic, J M; Chatellier, P

2001-02-01

In wastewater treatment, oxidation ditches are used for the removal of carbon and nitrogen of activated sludge. The control of the single-phase flow is essential to the optimisation of the whole process. Among the two global functioning parameters (mean liquid velocity Uc, power dissipated per unit of volume P/V), the mean circulation velocity can be recommended. Indeed, the values of the power dissipated per unit of volume P/V obtained in different scale plant show that the industrial criterion on P/V leads to an overdesign of channel. Therefore a mean liquid circulation velocity Uc created by horizontal impellers must be maintained inside the ditch. In order to predict the velocity Uc, a model has been proposed based on the Equations of the continuity and motion and using a few simple parameters. Experiments were carried out on pilot plant (1 m3) and full scale ditches (860, 1400 and 2800 m3) in which the characteristics of the mixing system and the dimensions of channels were varied. A good agreement was observed between the model predictions and experimental data for the mean circulation velocity Uc.

Intelligent agents as a basis for natural language interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chin, D.N.

1987-01-01

Typical natural-language interfaces respond passively to the users's commands and queries. They cannot volunteer information, correction user misconceptions, or reject unethical requests. In order to do these things, a system must be an intelligent agent. UC (UNIX Consultant), a natural language system that helps the user solve problems in using the UNIX operating system, is such an intelligent agent. The agent component of UC in UCEgo. UCEgo provides UC with its own goals and plans. By adopting different goals in different situations, UCEgo creates and executes different plans, enabling it to interact appropriately with the user. UCEgo adopts goals frommore » its themes, adopts subgoals during planning, and adopts metagoals for dealing with goal interactions. It also adopts goals when it notices that the user either lacks necessary knowledge, or has incorrect beliefs. In these cases, UCEgo plans to volunteer information or correct the user's misconception as appropriate. The user's knowledge and beliefs are modeled by the KNOME (KNOwledge Model of Expertise) component of UC. KNOME is a double-stereotype system which categorizes users by expertise and categorizes UNIX facts by difficulty.« less

Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort

PubMed Central

Bank, Steffen; Andersen, Paal Skytt; Burisch, Johan; Pedersen, Natalia; Roug, Stine; Galsgaard, Julied; Ydegaard Turino, Stine; Broder Brodersen, Jacob; Rashid, Shaista; Kaiser Rasmussen, Britt; Avlund, Sara; Bastholm Olesen, Thomas; Hoffmann, Hans Jürgen; Andersen Nexø, Bjørn; Sode, Jacob; Vogel, Ulla; Andersen, Vibeke

2015-01-01

Background The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC. Methods Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression. Results The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59–6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64–5.32, p = 0.005). Conclusion Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC. PMID:26698117

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study.

PubMed

Biancone, Livia; Zuzzi, Sara; Ranieri, Micaela; Petruzziello, Carmelina; Calabrese, Emma; Onali, Sara; Ascolani, Marta; Zorzi, Francesca; Condino, Giovanna; Iacobelli, Simona; Pallone, Francesco

2012-06-01

The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Blood-based biomarkers used to predict disease activity in Crohn's disease and ulcerative colitis.

PubMed

Burakoff, Robert; Pabby, Vikas; Onyewadume, Louisa; Odze, Robert; Adackapara, Cheryl; Wang, Wei; Friedman, Sonia; Hamilton, Matthew; Korzenik, Joshua; Levine, Jonathan; Makrauer, Frederick; Cheng, Changming; Smith, Hai Choo; Liew, Choong-Chin; Chao, Samuel

2015-05-01

Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC). Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC). Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data. The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.

Collaborative care for depression symptoms in an outpatient cardiology setting: A randomized clinical trial.

PubMed

Carney, Robert M; Freedland, Kenneth E; Steinmeyer, Brian C; Rubin, Eugene H; Ewald, Gregory

2016-09-15

Depression is a risk factor for morbidity and mortality in patients with coronary heart disease. Finding effective methods for identifying and treating depression in these patients is a high priority. The purpose of this study was to determine whether collaborative care (CC) for patients who screen positive for depression during an outpatient cardiology visit results in greater improvement in depression symptoms and better medical outcomes than seen in patients who screen positive for depression but receive only usual care (UC). Two hundred-one patients seen in an outpatient cardiology clinic who screened positive for depression during an outpatient visit were randomized to receive either CC or UC. Recommendations for depression treatment and ongoing support and monitoring of depression symptoms were provided to CC patients and their primary care physicians (PCPs) for up to 6months. There were no differences between the arms in mean Beck Depression Inventory-II scores(CC, 15.9; UC, 17.4; p=.45) or in depression remission rates(CC, 32.5%; UC, 26.2%; p=0.34) after 6months, or in the number of hospitalizations after 12months (p=0.73). There were fewer deaths among the CC (1/100) than UC patients (8/101) (p=0.03). This trial did not show that CC produces better depression outcomes than UC. Screening led to a higher rate of depression treatment than was expected in the UC group, and delays in obtaining depression treatment from PCPs may have reduced treatment effectiveness for the CC patients. A different strategy for depression treatment following screening in outpatient cardiology services is needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts entering puberty: a 3-year follow-up study.

PubMed

Võsoberg, Kristel; Tillmann, Vallo; Tamm, Anna-Liisa; Jürimäe, Toivo; Maasalu, Katre; Jürimäe, Jaak

2016-04-01

To investigate changes in bone mineral density (BMD) in rhythmic gymnasts (RG) entering puberty and their age-matched untrained controls (UC) over the 36-month period, and associations with leptin, adiponectin and ghrelin over this period. Whole body (WB), lumbar spine (LS) and femoral neck (FN) BMD, WB bone mineral content (BMC), and leptin, adiponectin and ghrelin were measured in 35 RG and 33 UC girls at baseline and at 12-month intervals over the next 3 years. The change over the 36 months was calculated (∆ score). The pubertal development over the next 36 months was slower in RG compard to UC, while there was no difference in bone age development between the groups. BMD at all sites was higher in RG in comparison with UC at every measurement point. ∆LS BMD and ∆FN BMD, but not ∆WB BMD and ∆WB BMC, were higher in RG compared with UC. None of the measured hormones at baseline or their ∆ scores correlated with ∆BMD and ∆BMC in RG. Baseline fat free mass correlated with ∆WB BMD and ∆WB BMC in RG, while baseline leptin was related to ∆WB BMC, ∆WB BMD and ∆LS BMD in UC. Measured baseline hormones and their ∆ scores did not correlate with increases in bone mineral values in RG entering puberty. Although the pubertal development in RG was slower than in UC, high-intensity training appeared to increase BMD growth and counterbalance negative effects of slow pubertal develpment, lower fat mass and leptin in RG.

Wnt5a / planar cell polarity signaling pathway in urothelial carcinoma, a potential prognostic biomarker

PubMed Central

Saling, Mark; Duckett, Jordan K; Ackers, Ian; Coschigano, Karen; Jenkinson, Scott; Malgor, Ramiro

2017-01-01

Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines. Formalin fixed and paraffin embedded transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E-cadherin. In addition, in vitro studies using UC cell lines were investigated for Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression. The IHC results showed a correlation between the expression of Wnt5a, Ror2 and CTHRC1 with high histological grade of the tumor, while E-cadherin showed an opposite trend of expression. Real time RT-PCR results showed that RNA expression of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that the high grade cell lines exhibited signs of EMT. These findings support that Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a prognostic marker and provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools. PMID:28427201

Simple cubic equation of state applied to hard-sphere, Lennard-Jones fluids, simple fluids and solids

NASA Astrophysics Data System (ADS)

Sun, Jiu-Xun; Cai, Ling-Cang; Wu, Qiang; Jin, Ke

2013-09-01

Based on the expansion and extension of the virial equation of state (EOS) of hard-sphere fluids solved by the Percus-Yevick integration equation, a universal cubic (UC) EOS is developed. The UC EOS is applied to model hard-sphere and Lennard-Jones (LJ) fluids, simple Ar and N2 liquids at low temperatures, and supercritical Ar and N2 fluids at high temperatures, as well as ten solids, respectively. The three parameters are determined for the hard-sphere fluid by fitting molecular dynamics (MD) simulation data of the third to eighth virial coefficients in the literature; for other fluids by fitting isothermal compression data; and for solids by using the Einstein model. The results show that the UC EOS gives better results than the Carnahan-Starling EOS for compressibility of hard-sphere fluids. The Helmholtz free energy and internal energy for LJ fluids are predicted and compared with MD simulation data. The calculated pressures for simple Ar and N2 liquids are compared with experimental data. The agreement is fairly good. Eight three-parameter EOSs are applied to describe isothermals of ten typical solids. It is shown that the UC EOS gives the best precision with correct behavior at high-pressure limitation. The UC EOS considering thermal effects is used to analytically evaluate the isobaric thermal expansivity and isothermal compressibility coefficients. The results are in good agreement with experimental data.

Cost-Effectiveness of Multidisciplinary Management Program and Exercise Training Program in Heart Failure.

PubMed

Dang, Weixiong; Yi, Anji; Jhamnani, Sunny; Wang, Shi-Yi

2017-10-15

Heart failure causes significant health and financial burdens for patients and society. Multidisciplinary management program (MMP) and exercise training program (ETP) have been reported as cost-effective in improving health outcomes, yet no study has compared the 2 programs. We constructed a Markov model to simulate life year (LY) gained and total costs in usual care (UC), MMP, and ETP. The probability of transitions between states and healthcare costs were extracted from previous literature. We calculated the incremental cost-effectiveness ratio (ICER) over a 10-year horizon. Model robustness was assessed through 1-way and probabilistic sensitivity analyses. The expected LY for patients treated with UC, MMP, and ETP was 7.6, 8.2, and 8.4 years, respectively. From a societal perspective, the expected cost of MMP was $20,695, slightly higher than the cost of UC ($20,092). The cost of ETP was much higher ($48,378) because of its high implementation expense and the wage loss it incurred. The ICER of MMP versus UC was $976 per LY gained, and the ICER of ETP versus MMP was $165,702 per LY gained. The results indicated that, under current cost-effectiveness threshold, MMP is cost-effective compared with UC, and ETP is not cost-effective compared with MMP. However, ETP is cost-effective compared with MMP from a healthcare payer's perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic characterization of UCS region of Pneumocystis jirovecii and construction of allelic profiles of Indian isolates based on sequence typing at three regions.

PubMed

Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Kumar, Lalit; Luthra, Kalpana; Agarwal, Sanjay Kumar; Sreenivas, Vishnubhatla

2013-01-01

Pneumocystis jirovecii is an opportunistic pathogen that causes severe pneumonia in immunocompromised patients. To study the genetic diversity of P. jirovecii in India the upstream conserved sequence (UCS) region of Pneumocystis genome was amplified, sequenced and genotyped from a set of respiratory specimens obtained from 50 patients with a positive result for nested mitochondrial large subunit ribosomal RNA (mtLSU rRNA) PCR during the years 2005-2008. Of these 50 cases, 45 showed a positive PCR for UCS region. Variations in the tandem repeats in UCS region were characterized by sequencing all the positive cases. Of the 45 cases, one case showed five repeats, 11 cases showed four repeats, 29 cases showed three repeats and four cases showed two repeats. By running amplified DNA from all these cases on a high-resolution gel, mixed infection was observed in 12 cases (26.7%, 12/45). Forty three of 45 cases included in this study had previously been typed at mtLSU rRNA and internal transcribed spacer (ITS) region by our group. In the present study, the genotypes at those two regions were combined with UCS repeat patterns to construct allelic profiles of 43 cases. A total of 36 allelic profiles were observed in 43 isolates indicating high genetic variability. A statistically significant association was observed between mtLSU rRNA genotype 1, ITS type Ea and UCS repeat pattern 4. Copyright © 2012 Elsevier B.V. All rights reserved.

Yokukansan in the treatment of behavioral and psychological symptoms of dementia: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Matsuda, Yuki; Kishi, Taro; Shibayama, Hiroto; Iwata, Nakao

2013-01-01

There is currently no meta-analysis of the efficacy and tolerability of Yokukansan in the treatment of behavioral and psychological symptoms of dementia. We used information obtained from the PubMed and Cochrane Library databases until October 2012. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing Yokukansan with usual care (UC, i.e., controls). Standardized mean difference and weighted mean difference were calculated. All studies used the Neuropsychiatric Inventory (NPI) for the evaluation of behavioral and psychological symptoms of dementia. Four relevant studies (total n = 236) were identified. Yokukansan was superior to UC in the reduction of total NPI scores (p = 0.0009, weighted mean difference = -7.20, I(2) = 0%). In addition, Yokukansan was more efficacious in reducing scores on the NPI subscale (delusions, hallucinations, and agitation/aggression) than UC (p < 0.00001-0.0009). Yokukansan treatment also improved activities of daily living scores compared with UC (p = 0.04, standardized mean difference = -0.32, I(2) = 0%). Mini-mental state examination scores did not differ between the Yokukansan and UC treatment groups. Yokukansan was not different from UC regarding discontinuation due to any cause. Our results suggest that Yokukansan has a beneficial effect on NPI and on ADL scores and that Yokukansan seems to be a well-tolerated treatment. Copyright © 2013 John Wiley & Sons, Ltd.

Physician Perspectives on Unresolved Issues in the Management of Ulcerative Colitis: The UC Horizons Project.

PubMed

Gisbert, Javier P; Barreiro-de Acosta, Manuel; Esteve, María; García-Sánchez, Valle; Gomollón, Fernando; Guardiola, Jordi; Hinojosa, Joaquin; Martín Arranz, Maria-Dolores; Minguez, Miguel; Taxonera, Carlos; Vera, Isabel

2016-03-01

There is still uncertainty about what constitutes the best therapeutic practice in ulcerative colitis (UC). The purpose of the "UC Horizons Project" was to raise a series of questions regarding the management of UC to provide responses based on the best scientific evidence available. The 11 members of the scientific committee prepared draft answers to the 10 questions from available evidence after a literature search. A total of 48 Spanish gastroenterology specialists nationwide participated in the project. The national meeting discussed the 10 issues in working groups and reached consensus regarding the recommendations by anonymous, interactive vote following the Delphi methodology. Final answers were developed, based on evidence and clinical experience of the participants. All the recommendations achieved a high level of agreement in the plenary vote, although the quality of the evidence was markedly heterogeneous. The lowest percentage of agreement corresponded to the questions with the weakest level of evidence, highlighting the necessity of conducting further studies in these areas. The recommendations focused on (1) aminosalicylates therapy (regarding dose and appropriateness of coadministration with thiopurines), (2) corticosteroid therapy (regarding dose and route of administration), (3) thiopurine treatment (regarding indications and possibility of withdrawal), (4) anti-tumor necrosis factor therapy (regarding appropriateness of combination with thiopurines, intensification, or discontinuation of treatment), and (5) colorectal cancer (regarding risk and time trends). The UC Horizons Project raised a series of eminently practical questions about the management of UC and provided responses based on the best scientific evidence available.

Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis.

PubMed

Shapira, Shiran; Leshno, Ari; Katz, Daniel; Maharshak, Nitsan; Hevroni, Gil; Jean-David, Maayan; Kraus, Sarah; Galazan, Lior; Aroch, Ilan; Kazanov, Dina; Hallack, Aharon; Becker, Stewart; Umanski, Mark; Moshkowitz, Menachem; Dotan, Iris; Arber, Nadir

2018-01-01

Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] in vivo and in patients with ulcerative colitis (UC). Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo versus the treated group ( p < 0.05). Selenium was the more active component. The contribution of green tea was minor. In the TNBS model, the Wallace scores for macroscopic lesions were 4.8 ± 1.5 (treatment) and 8.2 ± 0.5 (placebo) ( p = 0.01). In humans, Coltect was well tolerated and effective. Fourteen subjects (70%) improved: nine (45%) went into complete remission, four (20%) experienced marked improvement and one (5%) experienced moderate improvement at the end of the trial. Clinical activity index decreased significantly at 4 and 8 weeks ( p < 0.001). Two patients had no change in their symptoms, and one withdrew after 4 weeks. Flare-up in four subjects caused three to withdraw from the study after less than 4 weeks. Endoscopic improvement was observed in 11 (69%) patients, and four patients (25%) achieved complete remission. Coltect may serve as a first-line or add-on therapy in patients with mild-to-moderate UC.

Vedolizumab in Paediatric Inflammatory Bowel Disease: A Retrospective Multi-Centre Experience From the Paediatric IBD Porto Group of ESPGHAN.

PubMed

Ledder, Oren; Assa, Amit; Levine, Arie; Escher, Johanna C; de Ridder, Lissy; Ruemmele, Frank; Shah, Neil; Shaoul, Ron; Wolters, Victorien M; Rodrigues, Astor; Uhlig, Holm H; Posovsky, Carsten; Kolho, Kaija-Leena; Jakobsen, Christian; Cohen, Shlomi; Shouval, Dror S; de Meij, Tim; Martin-de-Carpi, Javier; Richmond, Lisa; Bronsky, Jiri; Friedman, Mira; Turner, Dan

2017-10-01

Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with inflammatory bowel disease [IBD], but the data in paediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-centre paediatric IBD cohort. Retrospective review of children [aged 2-18 years] treated with vedolizumab from 19 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was Week 14 corticosteroid-free remission [CFR]. In all, 64 children were included (32 [50%] male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks [interquartile range 14-38; range 6-116]); 41 [64%] cases of ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U] and 23 [36%] Crohn's disease [CD]. All were previously treated with anti-tumour necrosis factor [TNF] [28% primary failure, 53% secondary failure]. Week 14 CFR was 37% in UC, and 14% in CD [P = 0.06]. CFR by last follow-up was 39% in UC and 24% in CD [p = 0.24]. Ten [17%] children required surgery, six of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate [42% vs 35%; p = 0.35 at Week 22]. There were three minor drug-related adverse events. Only 3 of 16 children who underwent endoscopic evaluation had mucosal healing after treatment (19%). Vedolizumab was safe and effective in this cohort of paediatric refractory IBD. These data support previous findings of slow induction rate of vedolizumab in CD and a trend to be less effective compared with patients with UC. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Efficacy of Bifidobacterium breve Fermented Milk in Maintaining Remission of Ulcerative Colitis.

PubMed

Matsuoka, Katsuyoshi; Uemura, Yukari; Kanai, Takanori; Kunisaki, Reiko; Suzuki, Yasuo; Yokoyama, Kaoru; Yoshimura, Naoki; Hibi, Toshifumi

2018-02-15

Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients. To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC. This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC). An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient). BFM had no effect on time to relapse in UC patients compared with placebo. UMIN000007593.

The feasibility of a pragmatic randomised controlled trial to compare usual care with usual care plus individualised homeopathy, in children requiring secondary care for asthma.

PubMed

Thompson, E A; Shaw, A; Nichol, J; Hollinghurst, S; Henderson, A J; Thompson, T; Sharp, D

2011-07-01

To test the feasibility of a pragmatic trial design with economic evaluation and nested qualitative study, comparing usual care (UC) with UC plus individualised homeopathy, in children requiring secondary care for asthma. This included recruitment and retention, acceptability of outcome measures patients' and health professionals' views and experiences and a power calculation for a definitive trial. In a pragmatic parallel group randomised controlled trial (RCT) design, children on step 2 or above of the British Thoracic Society Asthma Guidelines (BTG) were randomly allocated to UC or UC plus a five visit package of homeopathic care (HC). Outcome measures included the Juniper Asthma Control Questionnaire, Quality of Life Questionnaire and a resource use questionnaire. Qualitative interviews were used to gain families' and health professionals' views and experiences. 226 children were identified from hospital clinics and related patient databases. 67 showed an interest in participating, 39 children were randomised, 18 to HC and 21 to UC. Evidence in favour of adjunctive homeopathic treatment was lacking. Economic evaluation suggests that the cost of additional consultations was not offset by the reduced cost of homeopathic remedies and the lower use of primary care by children in the homeopathic group. Qualitative data gave insights into the differing perspectives of families and health care professionals within the research process. A future study using this design is not feasible, further investigation of a potential role for homeopathy in asthma management might be better conducted in primary care with children with less severe asthma. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Preservation of Immune Function in Cervical Cancer Patients during Chemoradiation using a Novel Integrative Approach

PubMed Central

Lutgendorf, Susan K.; Mullen-Houser, Elizabeth; Russell, Daniel; DeGeest, Koen; Jacobson, Geraldine; Hart, Laura; Bender, David; Anderson, Barrie; Buekers, Thomas E.; Goodheart, Michael J.; Antoni, Michael H.; Sood, Anil K.; Lubaroff, David M.

2010-01-01

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for 1) supporting cellular immunity, 2) improving mood and quality of life (QOL), and 3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial assessments and blood sampling before chemoradiation at baseline, weeks 4 and 6. Multilevel regression analyses using orthogonal contrasts tested for differences between treatment conditions over time. HT patients had a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of RT and UC patients declined sharply during chemoradiation (group by time interaction: p=0.018). HT patients showed greater decreases in 2 different indicators of depressed mood (CESD depressed mood subscale and POMS depression scale) compared to RT and UC (group by time interactions: p < 0.05). No between group differences were observed in QOL, treatment delay, or clinically-rated toxicities. HT may benefit cervical cancer patients by moderating effects of chemoradiation on depressed mood and cellular immunity. Effects of HT on toxicities, treatment delay, QOL, and fatigue were not observed. Long-term clinical implications of findings are not known. PMID:20600809

Results of Student-Generated 'Unique Characteristics' on the Medical Student Performance Evaluation.

PubMed

Holloway, Richard; Domack, Aaron; Treat, Robert; Roo, Koenraad De

2016-06-01

The Medical Student Performance Evaluation (MSPE)--formerly called the dean's letter--is an important tool for residency program directors to use in assessing student qualifications for both invitation to interview and construction of their rank order list. Many institutions are now allowing students to construct their own Unique Characteristics (UC) section for the MSPE. This study addresses the results of allowing students to construct their own UC. The goal of this study was to allow students to voice their thoughts regarding their participation in the construction of the UC section of the MSPE. The survey evaluated student attitude toward, value of, and support for the UC section. We conducted a cross-sectional survey of all fourth-year medical students at the Medical College of Wisconsin during the 2014-2015 academic year. Responses were received from 66% of students (133 out of 199). We developed a question bank to cover the aims of the study--to assess student perceived value, experience writing, and support for the UC section. There was agreement among students that their participation will positively affect their candidacy for interview selection and success in the match. Overall significance of regression model P = .001, R2. = .60. Additionally, students believed they had an advantage over applicants at other schools without the opportunity to draft their UC. Other findings included that men found the task more challenging, psychiatry applicants were least satisfied with the character count, and emergency medicine applicants voiced the lowest value for the UC section. The present study supports, in general terms, the utility and value of students drafting their own UC section of the MSPE. Future investigations should focus on expanding to other schools, comparing public to private institutions, and refining the interspecialty comparisons.

Three-dimensional spheroid culture of human umbilical cord mesenchymal stem cells promotes cell yield and stemness maintenance.

PubMed

Li, Yi; Guo, Gang; Li, Li; Chen, Fei; Bao, Ji; Shi, Yu-Jun; Bu, Hong

2015-05-01

Mesenchymal stem cell (MSC) transplantation is a promising treatment of many diseases. However, conventional techniques with cells being cultured as a monolayer result in slow cell proliferation and insufficient yield to meet clinical demands. Three-dimensional (3D) culture systems are gaining attention with regard to recreating a complex microenvironment and to understanding the conditions experienced by cells. Our aim is to establish a novel 3D system for the culture of human umbilical cord MSCs (hUC-MSCs) within a real 3D microenvironment but with no digestion or passaging. Primary hUC-MSCs were isolated and grown in serum-free medium (SFM) on a suspension Rocker system. Cell characteristics including proliferation, phenotype and multipotency were recorded. The therapeutic effects of 3D-cultured hUC-MSCs on carbon tetrachloride (CCl4)-induced acute liver failure in mouse models were examined. In the 3D Rocker system, hUC-MSCs formed spheroids in SFM and maintained high viability and active proliferation. Compared with monolayer culture, the 3D-culture system yielded more hUC-MSCs cells within the same volume. The spheroids expressed higher levels of stem cell markers and displayed stronger multipotency. After transplantation into mouse, 3D hUC-MSCs significantly promoted the secretion of interferon-γ and interleukin-6 but inhibited that of tumor necrosis factor-α, thereby alleviating liver necrosis and promoting regeneration following CCl4 injury. The 3D culture of hUC-MSCs thus promotes cell yield and stemness maintenance and represents a promising strategy for hUC-MSCs expansion on an industrial scale with great potential for cell therapy and biotechnology.

Academic productivity and its relationship to physician salaries in the University of California Healthcare System.

PubMed

Fijalkowski, Natalia; Zheng, Luo Luo; Henderson, Michael T; Moshfeghi, Andrew A; Maltenfort, Mitchell; Moshfeghi, Darius M

2013-07-01

To evaluate whether physicians with higher academic productivity, as measured by the number of publications in Scopus and the Scopus Hirsch index (h-index), earn higher salaries. This was a cross-sectional study. Participants were ophthalmologists, otolaryngologists, neurosurgeons, and neurologists classified as "top earners" (>$100,000 annually) within the University of California (UC) healthcare system in 2008. Bibliometric searches on Scopus were conducted to retrieve the total number of publications and Hirsch indices (h-index), a measure of academic productivity. The association between the number of publications and h-index on physicians' total compensation was determined with multivariate regression models after controlling for the four specialties (ophthalmology, otolaryngology, neurosurgery, and neurology), the five institutions (UC San Francisco, UC Los Angeles, UC San Diego, UC Irvine, and UC Davis), and academic rank (assistant professor, associate professor, and professor). The UC healthcare system departments reported 433 faculty physicians among the four specialties, with 71.6% (n = 310) earning more than $100,000 in 2008 and classifying as top earners. After controlling for the specialty, institution, and ranking, there was a significant association between the number of publications on salary (P < 0.000001). Scopus number of publications and h-index were correlated (P < 0.001). Scopus h-index was of borderline significance in predicting physician salary (P = 0.12). Physicians with higher Scopus publications had higher total salaries across all four specialties. Every 10 publications were associated with a 2.40% increase in total salary after controlling for specialty, institution, rank, and chair. Ophthalmologists, otolaryngologists, neurosurgeons, and neurologists in the UC healthcare system who are more academically productive receive greater remuneration.

Human umbilical cord mesenchymal stem cells ameliorate mice trinitrobenzene sulfonic acid (TNBS)-induced colitis.

PubMed

Liang, Lu; Dong, Chunlan; Chen, Xiaojun; Fang, Zhihong; Xu, Jie; Liu, Meng; Zhang, Xiaoguang; Gu, Dong Sheng; Wang, Ding; Du, Weiting; Zhu, Delin; Han, Zhong Chao

2011-01-01

Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-γ and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-γ expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis.

Comparison of ultrasonic energy, bipolar thermal energy, and vascular clips for the hemostasis of small-, medium-, and large-sized arteries.

PubMed

Harold, K L; Pollinger, H; Matthews, B D; Kercher, K W; Sing, R F; Heniford, B T

2003-08-01

Advanced laparoscopic procedures have necessitated the development of new technology for vascular control. Suture ligation can be time-consuming and cumbersome during laparoscopic dissection. Titanium clips have been used for hemostasis, and recently plastic clips and energy sources such as ultrasonic coagulating shears and bipolar thermal energy devices have become popular. The purpose of this study was to compare the bursting pressure of arteries sealed with ultrasonic coagulating shears (UCS), electrothermal bipolar vessel sealer (EBVS), titanium laparoscopic clips (LCs), and plastic laparoscopic clips (PCs). In addition, the spread of thermal injury from the UCS and the EBVS was compared. Arteries in three size groups (2-3, 4-5 and 6-7 mm) were harvested from freshly euthanized pigs. Each of the four devices was used to seal 16 specimens from each size group for burst testing. A 5-Fr catheter was placed into the open end of the specimen and secured with a purse-string suture. The catheter was connected to a pressure monitor and saline was infused until there was leakage from the sealed end. This defined the bursting pressure in mmHg. The ultrasonic shears and bipolar thermal device were used to seal an additional 8 vessels in each size group, which were sent for histologic examination. These were examined with hematoxylin and eosin stains, and the extent of thermal injury, defined by coagulation necrosis, was measured in millimeters. Analysis of variance was performed and, where appropriate, a Tukey's test was also performed. The EBVS's mean burst pressure was statistically higher than that of the UCS at 4 or 5 mm (601 vs 205 mmHg) and 6 or 7 mm (442 vs 175 mmHg). EBVS had higher burst pressures for the 4 or 5-mm group (601 mmHg) and 6 or 7-mm group (442 mmHg) compared with its pressure at 2 or 3 mm (128 mmHg) ( p = 0.0001). The burst pressures of the UCS and EBVS at 2 or 3 mm were not significantly different. Both clips were statistically stronger than the thermal devices except at 4 or 5 mm, in which case the EBVS was as strong as the LC (601 vs 593 mmHg). The PC and LC were similar except at 4 or 5 mm, where the PC was superior (854 vs 593 mmHg). The PC burst pressure for 4 or 5 mm (854 mmHg) was statistically higher than that for vessels 2 or 3 mm (737 mmHg) but not different from the 6 or 7 mm pressure (767 mmHg). Thermal spread was not statistically different when comparing EBVS and UCS at any size (EBVS mean = 2.57 mm vs UCS mean = 2.18 mm). Both the PC and LC secured all vessel sizes to well above physiologic levels. The EBVS can be used confidently in vessels up to 7 mm. There is no difference in the thermal spread of the LigaSure vessel sealer and the UCS.

A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis.

PubMed

Rastegarpanah, Mansoor; Malekzadeh, Reza; Vahedi, Homayoun; Mohammadi, Maryam; Elahi, Elham; Chaharmahali, Meghedi; Safarnavadeh, Tahereh; Abdollahi, Mohammad

2015-12-01

To evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients. A randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data. Ten patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). Silymarin as a natural supplement may be used in UC patients to maintain remission.

Environmental factors in infancy and ulcerative colitis in the Central South of Chile: a case-control study.

PubMed

Boneberger, Anja; Weiss, Eduardo Hebel; Calvo, Mario; Torres, Lilibeth; Wagner, Johanna; Kabesch, Michael; Radon, Katja

2011-10-01

Evidence for the role of the hygiene hypothesis and the development of Ulcerative Colitis (UC) is unclear. We aimed to explore the association between environmental factors in infancy and UC. A hospital-based case-control study (52 UC cases, response: 77%, 174 age- , sex and place of living matched controls, response: 62%) was carried out in the Central South of Chile in 2009/2010. Patients or parents underwent a personal interview about early life experiences. High paternal education (adjusted Odds Ratio (aOR): 2.1; 95% CI: 1.0-4.5) as proxy for socioeconomic status was positively associated with case status in the final multivariate logistic regression model. Likewise, having older siblings was a risk factor for UC (aOR: 2.2; 95%CI: 1.1.-4.4). The importance for some early life environmental factors in the development of UC was established. However, the role of the hygiene hypothesis could not be confirmed for all environmental factors. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum.

PubMed

Flöck, A; Weber, S K; Ferrari, N; Fietz, C; Graf, C; Fimmers, R; Gembruch, U; Merz, W M

2016-01-01

Brain-derived neurotrophic factor (BDNF) plays a fundamental role in brain development; additionally, it is involved in various aspects of cerebral function, including neurodegenerative and psychiatric diseases. Involvement of BDNF in parturition has not been investigated. The aim of our study was to analyze determinants of umbilical cord BDNF (UC-BDNF) concentrations of healthy, term newborns and their respective mothers. This cross-sectional prospective study was performed at a tertiary referral center. Maternal venous blood samples were taken on admission to labor ward; newborn venous blood samples were drawn from the umbilical cord (UC), before delivery of the placenta. Analysis was performed with a commercially available immunoassay. Univariate analyses and stepwise multivariate regression models were applied. 120 patients were recruited. UC-BDNF levels were lower than maternal serum concentrations (median 641 ng/mL, IQR 506 vs. median 780 ng/mL, IQR 602). Correlation between UC- and maternal BDNF was low (R=0.251, p=0.01). In univariate analysis, mode of delivery (MoD), gestational age (GA), body mass index at delivery, and gestational diabetes were determinants of UC-BDNF (MoD and smoking for maternal BDNF, respectively). Stepwise multivariate regression analysis revealed a model with MoD and GA as determinants for UC-BDNF (MoD for maternal BDNF). MoD and GA at delivery are determinants of circulating BDNF in the mother and newborn. We hypothesize that BDNF, like other neuroendocrine factors, is involved in the neuroendocrine cascade of delivery. Timing and mode of delivery may exert BDNF-induced effects on the cerebral function of newborns and their mothers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

PubMed

Singh, Sunny; Al-Darmaki, Ahmed; Frolkis, Alexandra D; Seow, Cynthia H; Leung, Yvette; Novak, Kerri L; Ghosh, Subrata; Eksteen, Bertus; Panaccione, Remo; Kaplan, Gilaad G

2015-10-01

There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

PubMed

Ellinghaus, David; Folseraas, Trine; Holm, Kristian; Ellinghaus, Eva; Melum, Espen; Balschun, Tobias; Laerdahl, Jon K; Shiryaev, Alexey; Gotthardt, Daniel N; Weismüller, Tobias J; Schramm, Christoph; Wittig, Michael; Bergquist, Annika; Björnsson, Einar; Marschall, Hanns-Ulrich; Vatn, Morten; Teufel, Andreas; Rust, Christian; Gieger, Christian; Wichmann, H-Erich; Runz, Heiko; Sterneck, Martina; Rupp, Christian; Braun, Felix; Weersma, Rinse K; Wijmenga, Cisca; Ponsioen, Cyriel Y; Mathew, Christopher G; Rutgeerts, Paul; Vermeire, Séverine; Schrumpf, Erik; Hov, Johannes R; Manns, Michael P; Boberg, Kirsten M; Schreiber, Stefan; Franke, Andre; Karlsen, Tom H

2013-09-01

Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10(-9) in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10(-8) , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor. By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. Copyright © 2012 American Association for the Study of Liver Diseases.

Supplemental Report on Academic Salaries, 1987-88. A Report to the Governor and Legislature in Response to Senate Concurrent Resolution No. 51 (1965) and Subsequent Postsecondary Salary Legislation. Commission Report 88-30.

ERIC Educational Resources Information Center

California State Postsecondary Education Commission, Sacramento.

Data are presented on faculty and administrator salaries in the California community colleges, with comparative figures for the University of California (UC) and the California State University (CSU). Section 1 presents UC and CSU comparison group average salaries for 1982-83 and 1987-88, including information on compound rates of interest,…

The impact of Clostridum difficile on surgical rate among ulcerative colitis patients: A systemic review and meta-analysis.

PubMed

Peng, Jiang-Chen; Shen, Jun; Zhu, Qi; Ran, Zhi-Hua

2015-01-01

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case-control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36-2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.

A new test for the assessment of working memory in clinical settings: Validation and norming of a month ordering task.

PubMed

Buekenhout, Imke; Leitão, José; Gomes, Ana A

2018-05-24

Month ordering tasks have been used in experimental settings to obtain measures of working memory (WM) capacity in older/clinical groups based solely on their face validity. We sought to assess the appropriateness of using a month ordering task in other contexts, including clinical settings, as a psychometrically sound WM assessment. To this end, we constructed a month ordering task (ucMOT), studied its reliability (internal consistency and temporal stability), and gathered construct-related and criterion-related validity evidence for its use as a WM assessment. The ucMOT proved to be internally consistent and temporally stable, and analyses of the criterion-related validity evidence revealed that its scores predicted the efficiency of language comprehension processes known to depend crucially on WM resources, namely, processes involved in pronoun interpretation. Furthermore, all ucMOT items discriminated between younger and older age groups; the global scores were significantly correlated with scores on well-established WM tasks and presented lower correlations with instruments that evaluate different (although related) processes, namely, inhibition and processing speed. We conclude that the ucMOT possesses solid psychometric properties. Accordingly, we acquired normative data for the Portuguese population, which we present as a regression-based algorithm that yields z scores adjusted for age, gender, and years of formal education. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Strength Training to Enhance Early Recovery after Hematopoietic Stem Cell Transplantation.

PubMed

Hacker, Eileen Danaher; Collins, Eileen; Park, Chang; Peters, Tara; Patel, Pritesh; Rondelli, Damiano

2017-04-01

Intensive cancer treatment followed by hematopoietic stem cell transplantation (HCT) results in moderate to severe fatigue and physical inactivity, leading to diminished functional ability. The purpose of this study was to determine the efficacy of an exercise intervention, strength training to enhance early recovery (STEER), on physical activity, fatigue, muscle strength, functional ability, and quality of life after HCT. This single-blind, randomized clinical trial compared strength training (n = 33) to usual care plus attention control with health education (UC + AC with HE) (n = 34). Subjects were stratified by type of transplantation and age. STEER consisted of a comprehensive program of progressive resistance introduced during hospitalization and continued for 6 weeks after hospital discharge. Fatigue, physical activity, muscle strength, functional ability, and quality of life were assessed before HCT hospital admission and after intervention completion. Data were analyzed using split-plot analysis of variance. Significant time × group interactions effects were noted for fatigue (P = .04). The STEER group reported improvement in fatigue from baseline to after intervention whereas the UC + AC with HE group reported worsened fatigue from baseline to after intervention. Time (P < .001) and group effects (P = .05) were observed for physical activity. Physical activity declined from baseline to 6 weeks after hospitalization. The STEER group was more physically active. Functional ability tests (timed stair climb and timed up and go) resulted in a significant interaction effect (P = .03 and P = .05, respectively). Subjects in the UC + AC with HE group were significantly slower on both tests baseline to after intervention, whereas the STEER group's time remained stable. The STEER group completed both tests faster than the UC + AC with HE group after intervention. Study findings support the use of STEER after intensive cancer treatment and HCT. Strength training demonstrated positive effects on fatigue, physical activity, muscle strength, and functional ability. The exact recovery patterns between groups and over time varied; the STEER group either improved or maintained their status from baseline to after intervention (6 weeks after hospital discharge) whereas the health education group generally declined over time or did not change. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Adaptive Returns of Deficient Systemic Plasma Immunoglobulin G Levels as Rehabilitation Biomarker After Emergency Colectomy for Fulminant Ulcerative Colitis.

PubMed

Hawkins, Alexander T; Um, Jun W; M'Koma, Amosy E

2017-01-01

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment for ulcerative colitis (UC). Emergency colectomies are performed for fulminant colitis (ie, toxic megacolon, profuse bleeding, perforation, or sepsis). The RPC and IPAA involve manipulation of the proximal ileum, which may influence the essential physiological function of gut-associated lymphoid tissues. Circulating plasma immunoglobulin G (p-IgG) deficiency is observed in patients with fulminant UC. In addition, increased levels have been reported in colonic tissues of active UC compared with quiescent disease. We aimed to examine levels of p-IgG for clinical evaluation following emergency colectomies in patients with fulminant UC compared with patients with quiescent disease having elective RPC operations. In total 45 patients received an ileoanal pouch (IAP) due to UC. In all, 27 patients were men and 18 were women. The mean age was 34 years (range: 18-55). Because of fulminant UC, 26 patients had emergency subtotal colectomies with terminal ileostomy (TI). During second operation, the rectum was excised, and an IAP with diverting loop ileostomy (DLI) was performed. Nineteen patients had elective operations and had colectomies performed in conjunction with the pouch operation. Mucosectomy was performed in all groups. As a last procedure, the DLI was closed. Blood samples for immunoglobulin G (IgG) analyses were collected from each patient before the colectomy, after the colectomy with TI (before construction of the pouch), during the period with pouches (prior to DLI closure), and at 1, 2, and 3 years and at mean 13.7 years (range: 10-20) after DLI closure. Immunoglobulin G was determined by immunonephelometric assay technique. The statistics were analyzed by analysis of variance and linear regression. Preoperatively, p-IgG was significantly lower in the patients who had emergency operations compared with the group that had elective operations, 9.9 ± 3.0 vs 11.5 ± 3.3 g/L ( P  < .03). During the manipulative period with TI and/or DLI, the p-IgG levels were increased in both points, but the increase was not statistically significant ( P  = .26 and P  = .19). During functional IAP at 1, 2, and 3 years and at mean 13.7 years (range: 10-20), there was a statistical increase in p-IgG levels ( P  < .002, P  < .005, P  < .005, and P  < .0001) compared with preoperative levels. These changes did not correlate with episodes of pouchitis ( P  = .51). In patients having elective operations, p-IgG did not change preoperatively. After 12 months with functional pouches, the p-IgG levels were similar in both groups to the elective patient group preoperatively. In conclusion, p-IgG was found to be significantly lower in the emergency surgery patients compared with the elective surgery group preoperatively. This difference was probably due to increased losses and impaired gut lymphoid tissue production of IgG in the acute fulminant phase of UC. After 12 months of DLI closure, significant differences were no longer found between the emergency and elective surgery groups. Restoration and increased p-IgG levels after RPC would be due to an exaggerated response to make up for lower precolectomy values and may be interpreted as a rehabilitation biomarker.

Lower rate-pressure product during submaximal walking: a link to fatigue improvement following a physical activity intervention among breast cancer survivors.

PubMed

Carter, Stephen J; Hunter, Gary R; McAuley, Edward; Courneya, Kerry S; Anton, Philip M; Rogers, Laura Q

2016-10-01

Research showing a link between exercise-induced changes in aerobic fitness and reduced fatigue after a cancer diagnosis has been inconsistent. We evaluated associations of fatigue and rate-pressure product (RPP), a reliable index of myocardial oxygen demand, at rest and during submaximal walking following a physical activity intervention among post-primary treatment breast cancer survivors (BCS). Secondary analyses of 152 BCS in a randomized controlled trial testing a physical activity intervention (INT) versus usual care (UC) were performed. The INT group completed counseling/group discussions along with supervised exercise sessions tapered to unsupervised exercise. Evaluations were made at baseline and immediately post-intervention (M3) on measures of physical activity (accelerometry), graded walk test, and average fatigue over the previous 7 days. RPP was calculated by dividing the product of heart rate and systolic blood pressure by 100. Resting and submaximal RPPs were significantly improved in both groups at M3; however, the magnitude of change (∆) was greater in the INT group from stage 1 (∆RPP1; INT -13 ± 17 vs. UC -7 ± 18; p = 0.03) through stage 4 (∆RPP4; INT -21 ± 26 vs. UC -9 ± 24; p < 0.01) of the walk test. The INT group reported significantly reduced fatigue (INT -0.7 ± 2.0 vs. UC +0.1 ± 2.0; p = 0.02) which was positively associated with ∆RPP during stages 2-4 of the walk test but not ∆aerobic fitness. Lower RPP during submaximal walking was significantly associated with reduced fatigue in BCS. Exercise/physical activity training programs that lower the physiological strain during submaximal walking may produce the largest improvements in reported fatigue.

Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis.

PubMed

Kurtys, E; Doorduin, J; Eisel, U L M; Dierckx, R A J O; de Vries, E F J

2017-02-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [ 11 C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated. Colitis was induced in rats by intra-rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [ 11 C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [ 11 C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation. Eleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [ 11 C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [ 11 C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11. Inflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [ 11 C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera.

Distinctions among agency, communion, and unmitigated agency and communion according to the interpersonal circumplex, Five-factor model, and social-emotional correlates.

PubMed

Ghaed, Shiva G; Gallo, Linda C

2006-02-01

In this study, we examined common measures of agency (AG), communion (CM), and unmitigated agency (UA) and unmitigated communion (UC) using the interpersonal circumplex and Five-factor models (FFM) as conceptual frameworks. AG aligned with interpersonal dominance in circumplex space and related positively to conscientiousness and inversely to neuroticism. CM corresponded with interpersonal affiliation and related positively to conscientiousness. UA was consistent with hostile-dominance and related to lower conscientiousness and higher neuroticism. UC related to friendly submission but was not strongly represented in the circumplex and did not relate to the FFM. Each construct showed distinct social-emotional correlates. These findings support the convergent and divergent properties of the constructs but suggest that additional attention to the conceptual definition and measurement of UC is warranted.

Disease-specific Alterations in the Enteric Virome in Inflammatory Bowel Disease

PubMed Central

Norman, Jason M.; Handley, Scott A.; Baldridge, Megan T.; Droit, Lindsay; Liu, Catherine Y.; Keller, Brian C.; Kambal, Amal; Monaco, Cynthia L.; Zhao, Guoyan; Fleshner, Phillip; Stappenbeck, Thaddeus S.; McGovern, Dermot P.B.; Keshavarzian, Ali; Mutlu, Ece A.; Sauk, Jenny; Gevers, Dirk; Xavier, Ramnik J.; Wang, David; Parkes, Miles; Virgin, Herbert W.

2015-01-01

SUMMARY Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease- and cohort-specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases. PMID:25619688

Development of a UC781 releasing polyethylene vinyl acetate vaginal ring.

PubMed

McConville, Christopher; Major, Ian; Friend, David R; Clark, Meredith R; Malcolm, R Karl

2012-12-01

UC781 is potent, hydrophobic, non-nucleotide reverse transcriptase inhibitor (NNRTI) against the human immunodeficiency virus (HIV). UC781 is currently being investigated for use as a potential HIV microbicide. A study in rhesus macaques demonstrated that a 100-mg UC781-loaded silicone elastomer vaginal ring released limited amounts of UC781 into the vaginal fluid and tissue after 28 days. The reason for this was due to the hydrophobic nature and limited aqueous solubility of UC781. This study describes the manufacture of UC781-loaded polyethylene vinyl acetate (PEVA) vaginal rings, which have an improved in vitro release rate of UC781 when compared to UC781-loaded silicone elastomer vaginal rings. The study demonstrates that the UC781 in the PEVA rings is mostly in its amorphous form due to the rings being manufactured above UC781's melting point. Furthermore, the rings do not show any signs of UC781 degradation, such as the presence of UC22.

Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: behavioral and neuropathological analysis

PubMed Central

2013-01-01

Introduction Huntington’s disease (HD) is an autosomal dominant disorder caused by an expanded CAG repeat on the short arm of chromosome 4 resulting in cognitive decline, motor dysfunction, and death, typically occurring 15 to 20 years after the onset of motor symptoms. Neuropathologically, HD is characterized by a specific loss of medium spiny neurons in the caudate and the putamen, as well as subsequent neuronal loss in the cerebral cortex. The transgenic R6/2 mouse model of HD carries the N-terminal fragment of the human HD gene (145 to 155 repeats) and rapidly develops some of the behavioral characteristics that are analogous to the human form of the disease. Mesenchymal stem cells (MSCs) have shown the ability to slow the onset of behavioral and neuropathological deficits following intrastriatal transplantation in rodent models of HD. Use of MSCs derived from umbilical cord (UC) offers an attractive strategy for transplantation as these cells are isolated from a noncontroversial and inexhaustible source and can be harvested at a low cost. Because UC MSCs represent an intermediate link between adult and embryonic tissue, they may hold more pluripotent properties than adult stem cells derived from other sources. Methods Mesenchymal stem cells, isolated from the UC of day 15 gestation pups, were transplanted intrastriatally into 5-week-old R6/2 mice at either a low-passage (3 to 8) or high-passage (40 to 50). Mice were tested behaviorally for 6 weeks using the rotarod task, the Morris water maze, and the limb-clasping response. Following behavioral testing, tissue sections were analyzed for UC MSC survival, the immune response to the transplanted cells, and neuropathological changes. Results Following transplantation of UC MSCs, R6/2 mice did not display a reduction in motor deficits but there appeared to be transient sparing in a spatial memory task when compared to untreated R6/2 mice. However, R6/2 mice receiving either low- or high-passage UC MSCs displayed significantly less neuropathological deficits, relative to untreated R6/2 mice. Conclusions The results from this study demonstrate that UC MSCs hold promise for reducing the neuropathological deficits observed in the R6/2 rodent model of HD. PMID:24456799

Efficacy of long-term 4.0 g/day mesalazine (Pentasa) for maintenance therapy in ulcerative colitis.

PubMed

Takeshima, Fuminao; Matsumura, Masato; Makiyama, Kazuya; Ohba, Kazuo; Yamakawa, Masaki; Nishiyama, Hitoshi; Yamao, Takuji; Akazawa, Yuko; Yamaguchi, Naoyuki; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

2014-07-27

High-dose (4.0 g/day) mesalazine is typically used for induction therapy, but its efficacy as maintenance therapy remains to be determined. We conducted a multicenter retrospective study to investigate the efficacy of continuous treatment with 4.0 g/day of mesalazine. Japanese ulcerative colitis (UC) patients receiving acute induction therapy with 4.0 g/day mesalazine were enrolled and followed. Those who clinically improved or who achieved clinical remission were categorized into 2 sub-groups according to the median duration of treatment with 4.0 g/day of mesalazine. The clinical relapse frequency and the time to relapse were analyzed. We enrolled 180 patients with active UC, and then 115 patients who clinically improved or who achieved clinical remission after treatment with 4.0 g/day mesalazine were categorized into 2 sub-groups according to the median of treatment duration: a short-term treatment group (≤105 days, n=58) and a long-term treatment group (>105 days, n=57). Overall, 45 (39.1%) patients relapsed: 28 (48.3%) in the short-term treatment group and 17 (29.8%) in the long-term treatment group. This difference was statistically significant (p<0.05). The relapse-free rate in the long-term treatment group was significantly higher than that in the short-term treatment group (p<0.05). The mean time to relapse in the long-term treatment group was significantly longer than that in the short-term treatment group (425.6±243.8 days vs. 277.4±224.5 days; p<0.05). Long-term continuous treatment with high-dose mesalazine (4.0 g/day) may be more effective than short-term treatment for maintenance of remission in UC patients.

Impact of adipose tissue or umbilical cord derived mesenchymal stem cells on the immunogenicity of human cord blood derived endothelial progenitor cells

PubMed Central

Tan, Kefang; Zheng, Ke; Li, Daiye; Lu, Haiyuan; Wang, Siqi; Sun, Xuan

2017-01-01

The application of autologous endothelial progenitor cell (EPC) transplantation is a promising approach in therapeutic cardiovascular diseases and ischemic diseases. In this study, we compared the immunogenicity of EPCs, adipose tissue (AD)-derived mesenchymal stem cells (MSCs) and umbilical cord (UC)-derived MSCs by flow cytometry and the mixed lymphocyte reaction. The impact of AD-MSCs and UC-MSCs on the immunogenicity of EPCs was analyzed by the mixed lymphocyte reaction and cytokine secretion in vitro and was further tested by allogenic peripheral blood mononuclear cell (PBMC) induced immuno-rejection on a cell/matrigel graft in an SCID mouse model. EPCs and AD-MSCs express higher levels of MHC class I than UC-MSCs. All three kinds of cells are negative for MHC class II. UC-MSCs also express lower levels of IFN-γ receptor mRNA when compared with EPCs and AD-MSCs. EPCs can stimulate higher rates of proliferation of lymphocytes than AD-MSCs and UC-MSCs. Furthermore, AD-MSCs and UC-MSCs can modulate immune response and inhibit lymphocyte proliferation induced by EPCs, mainly through inhibition of the proliferation of CD8+ T cells. Compared with UC-MSCs, AD-MSCs can significantly improve vessel formation and maintain the integrity of neovascular structure in an EPC+MSC/matrigel graft in SCID mice, especially under allo-PBMC induced immuno-rejection. In conclusion, our study shows that AD-MSC is a powerful candidate to minimize immunological rejection and improve vessel formation in EPC transplantation treatment. PMID:28562647

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis.

PubMed

Soon, Ing Shian; Molodecky, Natalie A; Rabi, Doreen M; Ghali, William A; Barkema, Herman W; Kaplan, Gilaad G

2012-05-24

The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

PubMed

Romberg-Camps, M J L; Dagnelie, P C; Kester, A D M; Hesselink-van de Kruijs, M A M; Cilissen, M; Engels, L G J B; Van Deursen, C; Hameeteman, W H A; Wolters, F L; Russel, M G V M; Stockbrügger, R W

2009-02-01

Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Using Optical Markers of Non-dysplastic Rectal Epithelial Cells to Identify Patients With Ulcerative Colitis (UC) - Associated Neoplasia

PubMed Central

Bista, Rajan K.; Brentnall, Teresa A.; Bronner, Mary P.; Langmead, Christopher J.; Brand, Randall E.; Liu, Yang

2011-01-01

BACKGROUND Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study is to evaluate whether optical markers of rectal mucosa derived from a novel optical technique – partial-wave spectroscopic microscopy (PWS) could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. METHODS Banked frozen non-dysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. RESULTS We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. CONCLUSIONS Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for a high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. PMID:21351200

Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.

PubMed

Ţieranu, Cristian George; Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Popa, Caterina; Mănuc, Mircea; Ţieranu, Ioana; Preda, Carmen Monica; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

2017-01-01

Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

PubMed Central

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Sánchez-Osorio, Magdalena; Uribe, Misael

2010-01-01

To investigate the prevalence of abnormal function liver tests and risk factors associated with their development in Mexican patients with UC. A total of 200 patients with confirmed diagnosis of UC were evaluated prospectively during a one year period from January 1, 2007 to December 31, 2008. A total of 94 females and 106 males patients with UC were analyzed. The age at diagnosis was 31.4 ± 13.2 years and the mean of disease duration was 6.7 ± 5.2 years. We found a high prevalence of abnormal function livers tests in 40% of UC patients. The pattern of abnormal function liver test was hepatitis in 70%, cholestatic (20%) and mixed (10%). The most common cause of abnormal function liver test was transient elevation in 50 patients (63%) followed by fatty liver disease (11.2%), primary sclerosing cholangitis (6.3%), drug-toxicity (6%) and others (13.5%) including chronic hepatitis C, total parenteral nutrition, granulomatous and ischemic hepatitis. In the multivariate logistic regression model, active disease, colectomy and abdominal sepsis were factors that persisted associated with the development of abnormal liver tests in UC patients. A high prevalence of abnormal function liver tests (40%) was found in Mexican UC patients is likely to be related to active disease, colectomy and the presence of sepsis.

Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

PubMed

Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

2016-01-01

Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.

The Effects of a Mindfulness Meditation Program on Quality of Life in Cancer Outpatients: An Exploratory Study.

PubMed

Chang, Yu-Yun; Wang, Li-Yu; Liu, Chia-Yu; Chien, Tsai-Ju; Chen, I-Ju; Hsu, Chung-Hua

2018-06-01

Numerous studies have investigated the efficacy of mindfulness meditation (MM) in managing quality of life (QoL) in cancer populations, yet only a few have studied the Asian population. The aim of this exploratory study is to evaluate the effect of a MM program on the QoL outcomes in Taiwanese cancer outpatients. Patients with various cancer diagnoses were enrolled and assigned to the MM group and usual care (UC) group. The meditation intervention consisted of 3 sessions held monthly. The outcomes of the whole intervention were measured using the World Health Organization Quality of Life (WHOQOL-BREF) instrument. A total of 35 participants in the MM group and 34 in the UC group completed the study. The results showed that the postintervention scores were significantly higher than the preintervention scores in the MM group. In the UC group, there was no significant difference between preintervention and postintervention scores, except for the lower environment domain scores. There was no significant difference between the follow-up scores and postintervention scores in the MM group, indicating that improvement can be maintained for 3 months after completing the MM course. The present study provides preliminary outcomes of the effects on the QoL in Taiwanese cancer patients. The results suggest that MM may serve as an effective mind-body intervention for cancer patients to improve their QoL, and the benefits can persist over a 3-month follow-up period. This occurred in a diverse cancer population with various cancer diagnoses, strengthening the possibility of general use.

[Technique of thulium laser in managing bladder cuff in nephroureterectomy for upper urinary tract urothelium carcinoma].

PubMed

Pang, Kun; Sun, Xiao-Wen; Liu, Shi-Bo; Li, Wei-Guo; Shao, Yi; Zhuo, Jian; Wei, Hai-Bin; Xia, Shu-Jie

2012-11-13

To explore the application of thulium laser (2 µm laser) in managing bladder cuff in nephroureterectomy for upper urinary tract urothelium carcinoma (UUT-UC). The medical records of 56 patients undergoing nephroureterectomy at our hospital were reviewed retrospectively. The operative indicators, oncologic outcomes and clinicopathologic data were compared among the groups of open surgery (Group A), electric coagulation (Group B) and thulium laser technique (Group C). Furthermore a model of burst pressure measurement was built to measure the different burst pressures of sealing distal ureter. The follow-up results: when the indicators of operative duration, intraoperative blood loss volume, removal time of drainage tube, removal time of catheter and hospital stays were compared among three groups, Group A had no statistical differences with Group B/C in terms of removal time of drainage tube and removal time of catheter. But significant statistical differences existed in terms of operative duration, intraoperative blood loss volume and hospital stays ((232 ± 52) vs (148 ± 47) and (130 ± 49) min, (358 ± 81) vs (136 ± 74) and (145 ± 70) ml, (13 ± 3) vs (11 ± 4) and (10 ± 3) d, all P < 0.05). No statistical differences existed between Groups B and C in terms of all the above indicators. Burst pressure measurement results: no statistical differences existed between Group C and B ((116 ± 21) vs (139 ± 32) cm H2O, P > 0.05). For the surgical treatment of UUT-UC, thulium laser technique has no difference in operation indicators and oncologic outcomes compared to open surgery. Besides, it has the advantages of improved spatial beam quality and more precise tissue incision.

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

PubMed

Langhorst, J; Varnhagen, I; Schneider, S B; Albrecht, U; Rueffer, A; Stange, R; Michalsen, A; Dobos, G J

2013-09-01

The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18. © 2013 John Wiley & Sons Ltd.

Thailand's universal coverage scheme and its impact on health-seeking behavior.

PubMed

Paek, Seung Chun; Meemon, Natthani; Wan, Thomas T H

2016-01-01

Thailand's Universal Coverage Scheme (UCS) has improved healthcare access and utilization since its initial introduction in 2002. However, a substantial proportion of beneficiaries has utilized care outside the UCS boundaries. Because low utilization may be an indication of a policy gap between people's health needs and the services available to them, we investigated the patterns of health-seeking behavior and their social/contextual determinants among UCS beneficiaries in the year 2013. The study findings from the outpatient analysis showed that the use of designated facilities for care was significantly higher in low-income, unemployed, and chronic status groups. The findings from the inpatient analysis showed that the use of designated facilities for care was significantly higher in the low-income, older, and female groups. Particularly, for the low-income group, we found that they (1) had greater health care needs, (2) received a larger number of services from designated facilities, and (3) paid the least for both inpatient and outpatient services. This pro-poor impact indicated that the UCS could adequately respond to beneficiaries' needs in terms of vertical equity. However, we also found that a considerable proportion of beneficiaries utilized out-of-network services, which implied a lack of universal access to policy services from a horizontal equity point of view. Thus, the policy should continue expanding and diversifying its service benefits to strengthen horizontal equity. Particularly, private sector involvement for those who are employed as well as the increased unmet health needs of those in rural areas may be important policy priorities for that. Lastly, methodological issues such as severity adjustment and a detailed categorization of health-seeking behaviors need to be further considered for a better understanding of the policy impact.

Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study.

PubMed

Vergnaud, P; Garnero, P; Meunier, P J; Bréart, G; Kamihagi, K; Delmas, P D

1997-03-01

Increased levels of circulating undercarboxylated osteocalcin (ucOC), measured indirectly with the hydroxyapatite (HAP) binding assay, have been shown to predict hip fracture risk in a small group of elderly institutionalized women. The aim of this study was to confirm these findings in a prospective cohort study (EPIDOS prospective study) of 7598 healthy, independently living women over 75 yr of age. One hundred and four women who sustained a hip fracture during a 22-month follow-up period were age matched with 255 controls who did not fracture. Baseline samples were collected before hip fracture for measurement of total OC and ucOC, assessed either with the HAP binding assay or directly with a new enzyme-linked immunosorbent assay (ELISA). This direct ELISA uses human recombinant noncarboxylated OC as a standard and two monoclonal antibodies, one of which was raised against the 14-30 Glu synthetic peptide. We found that the intra- and interassay variations are less than 11%, and this assay exhibits a 5% cross-reactivity with purified human bone OC, used as a source of carboxylated OC. ucOC levels measured with this ELISA correlated well with the HAP binding assay in the population of 359 elderly women (r = 0.82; P < 0.0001). We estimated the risk of hip fracture for women with levels of ucOC in the highest quartile of values for the 255 controls. We found that increased levels of ucOC measured by ELISA were associated with increased hip fracture risk with an odds ratio (OR) of 1.9 (95% confidence interval, 1.2-3.0), and the ELISA had a greater sensitivity than the HAP assay. In contrast, total OC was not associated with hip fracture risk. After adjustment for femoral neck bone mineral density (BMD) and mobility status assessed by gait speed, ucOC still predicted hip fracture with an OR of 1.8 (1.0-3.0). Women with both femoral neck BMD in the lowest quartile and ucOC in the highest quartile were at higher risk of hip fracture, with an OR of 5.5 (2.7-11.2), than those with only low BMD or high ucOC levels. In conclusion, we have developed a new specific ELISA for serum ucOC, with low cross-reactivity with carboxylated OC and increased specificity and sensitivity over the HAP assay. Using this new ELISA, we found that ucOC, but not total OC, predicts hip fracture risk independently of femoral neck BMD in elderly women drawn from the general population. Thus, ucOC measurement could be combined with bone mass determination to improve the assessment of hip fracture risk in elderly women.

Efficacy and Safety of Beclomethasone Dipropionate versus 5-Aminosalicylic Acid in the Treatment of Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Zhao, Xin; Li, Nan; Ren, YiMing; Ma, Tao; Wang, ChunLi; Wang, Jun; You, ShengYi

2016-01-01

Ulcerative colitis (UC) is a chronic and remitting inflammatory disease that is characterized by chronic idiopathic inflammation of the colon and bloody diarrhea. Currently drug treatment is the main intervention for patients with mild to moderate UC. Mesalazine (5-ASA) and beclomethasone dipropionate (BDP) have been widely used for the treatment of UC and have yielded satisfactory results. This study compared the effectiveness of 5-ASA and BDP in the treatment of UC. The PubMed, Medline, SinoMed, Embase, and Cochrane Librinary databases were searched for eligible studies. Data were extracted by two of the coauthors independently and were analyzed using RevMan statistical software, version 5.3. Weighted mean differences (WMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Seven randomized controlled trials that compared BDP with 5-ASA in treating UC were identified as eligible. The methodological quality of the trials ranged from low to moderate. A pooled analysis of effectiveness based on the Disease Activity Index (DAI) or other assessment method after treatment revealed that in the treatment of UC, there are no obvious differences between BDP and 5-ASA in inducing remission and clinical improvement (OR = 0.76, 95% CI = 0.56-1.03, P = 0.08). The total numbers of adverse events associated with BDP and 5-ASA treatments for UC were similar (OR = 1.21, 95% CI = 0.71-2.09, P = 0.48). The safety profiles for these two drugs are good. According to subgroup-analysis, we found no obvious differences of clinical efficacy between BDP and 5-ASA no matter oral or enema administration was used in the treatment of UC. A sensitivity analysis demonstrated the stability of the pooled results. During induction treatment of mild to moderate UC, there is no obvious difference between the two groups with respect to remission and clinical improvement. Given that the upper confidence limit for the OR barely exceeds 1.0 and that the p-value is close to 0.05 for this primary efficacy outcome as well as that the horizontal block lies to the left of the vertical line, it indicates that the clinical efficacy of BDP may be better than 5-ASA. However, taking into account that BDP has the risk of hypothalamic-pituitary-adrenal axis (HPA) suppression, 5-ASA has a potential advantage of safety in the treatment of mild to moderate UC.

Effect of threatening life experiences and adverse family relations in ulcerative colitis: analysis using structural equation modeling and comparison with Crohn's disease.

PubMed

Slonim-Nevo, Vered; Sarid, Orly; Friger, Michael; Schwartz, Doron; Sergienko, Ruslan; Pereg, Avihu; Vardi, Hillel; Singer, Terri; Chernin, Elena; Greenberg, Dan; Odes, Shmuel

2017-05-01

We published that threatening life experiences and adverse family relations impact Crohn's disease (CD) adversely. In this study, we examine the influence of these stressors in ulcerative colitis (UC). Patients completed demography, economic status (ES), the Patient-Simple Clinical Colitis Activity Index (P-SCCAI), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Short-Form Health Survey (SF-36), the Brief Symptom Inventory (BSI), the Family Assessment Device (FAD), and the List of Threatening Life Experiences (LTE). Analysis included multiple linear and quantile regressions and structural equation modeling, comparing CD. UC patients (N=148, age 47.55±16.04 years, 50.6% women) had scores [median (interquartile range)] as follows: SCAAI, 2 (0.3-4.8); FAD, 1.8 (1.3-2.2); LTE, 1.0 (0-2.0); SF-36 Physical Health, 49.4 (36.8-55.1); SF-36 Mental Health, 45 (33.6-54.5); Brief Symptom Inventory-Global Severity Index (GSI), 0.5 (0.2-1.0). SIBDQ was 49.76±14.91. There were significant positive associations for LTE and SCAAI (25, 50, 75% quantiles), FAD and SF-36 Mental Health, FAD and LTE with GSI (50, 75, 90% quantiles), and ES with SF-36 and SIBDQ. The negative associations were as follows: LTE with SF-36 Physical/Mental Health, SIBDQ with FAD and LTE, ES with GSI (all quantiles), and P-SCCAI (75, 90% quantiles). In structural equation modeling analysis, LTE impacted ES negatively and ES impacted GSI negatively; LTE impacted GSI positively and GSI impacted P-SCCAI positively. In a split model, ES had a greater effect on GSI in UC than CD, whereas other path magnitudes were similar. Threatening life experiences, adverse family relations, and poor ES make UC patients less healthy both physically and mentally. The impact of ES is worse in UC than CD.

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

PubMed Central

Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

Background The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. Methods A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Results Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. Conclusions The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted. PMID:26023918

Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided ulcerative colitis.

PubMed

Celasco, G; Papa, A; Jones, R; Moro, L; Bozzella, R; Surace, M M; Naccari, G C; Gasbarrini, G

2010-02-01

The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX) has been proposed as a novel approach for the treatment of ulcerative colitis (UC). To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates. This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS). A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005). CB-01-05 MMX was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.

Shared Medical Appointments: Impact on Clinical and Quality Outcomes in Veterans With Diabetes.

PubMed

Harris, Marianne D; Kirsh, Susan; Higgins, Patricia A

2016-01-01

Managing diabetes poses substantial challenges to the over 29.1 million Americans afflicted, and is financially overwhelming to the US health care system. One potential strategy is utilizing a group approach to care delivery or shared medical appointment (SMA). The purpose of this 3-year retrospective VA study was to investigate differences in clinical and quality outcome measures in veterans with type 2 diabetes who used SMAs and those who received only usual care (UC) one-on-one with their doctor. This observational, 2-group cohort study used abstracted medical records from a large Midwestern Veterans Administration hospital. Clinical outcome metrics included hemoglobin A1c (hbA1c), systolic blood pressure, low-density lipoprotein cholesterol, and emergency department (ED) visits. Quality outcomes included Veterans' Administration (VA) Department of Defense clinical practice guidelines for the management of diabetes. A total of 988 total VA cases were examined retrospectively over 3 years: 371 cases had used SMAs and 617 were in the UC cohort, and had never attended a diabetes SMA. The study period used abstracted VA medical records from 2008 to 2010. There were no statistically significant differences in HbA1c, systolic blood pressure, and ED visits between groups; however, hbA1c for individuals who attended SMAs was 8.55 (standard deviation [SD] = 1.72) and UC was 7.49 (SD = 1.28) (P < .001). All clinical outcomes were worse at baseline for the SMA cohort. UC had mean ED visits/3 years (mean = 18.62, SD = 13.53, P < .001) versus SMA participants (mean = 27.97, SD = 14.00, P <. 001), revealing a propensity for high health care utilization. SMA providers had statistically significant differences over UC cases on quality measures, including ordering annual ophthalmology and podiatry examinations (P < .001) and prescribing aspirin and angiotension-converting enzyme inhibitors (ACE-I). SMAs may provide a venue for assessing and delivering quality care for patients with type 2 diabetes. More research is needed to ascertain effective strategies for diabetes disease management in high-risk patients.

Cost-Utility Analysis of Pharmaceutical Care Intervention Versus Usual Care in Management of Nigerian Patients with Type 2 Diabetes.

PubMed

Adibe, Maxwell O; Aguwa, Cletus N; Ukwe, Chinwe V

To assess the cost-effectiveness of pharmaceutical care (PC) intervention versus usual care (UC) in the management of type 2 diabetes. This study was a randomized, controlled study with a 12-month patient follow-up in two Nigerian tertiary hospitals. One hundred and ten patients were randomly assigned to each of the "intervention" (PC) and the "control" (UC) groups. Patients in the UC group received the usual/conventional care offered by the hospitals. Patients in the PC group received UC and PC in the form of structural self-care education and training for 12 months. The economic evaluation was based on patients' perspective. Costs of management of individual complications were calculated from activities involved in their management by using activity-based costing. The impact of the interventions on quality of life was estimated by using the HUI23S4EN.40Q (Mark index 3) questionnaire. The primary outcomes were incremental cost-utility ratio and net monetary benefit. An intention-to-treat approach was used. Two-sample comparisons were made by using Student's t tests for normally distributed variables data at baseline, 6 months, and 12 months. Comparisons of proportions were done by using the chi-square test. The PC intervention led to incremental cost and effect of Nigerian naira (NGN) 10,623 ($69) and 0.12 quality-adjusted life-year (QALY) gained, respectively, with an associated incremental cost-utility ratio of NGN 88,525 ($571) per QALY gained. In the cost-effectiveness acceptability curve, the probability that PC was more cost-effective than UC was 95% at the NGN 250,000 ($1613) per QALY gained threshold and 52% at the NGN 88,600 ($572) per QALY gained threshold. The PC intervention was very cost-effective among patients with type 2 diabetes at the NGN 88,525 ($571.13) per QALY gained threshold, although considerable uncertainty surrounds these estimates. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared with 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial

PubMed Central

Hanauer, Stephen B; Sandborn, William J; Dallaire, Christian; Archambault, André; Yacyshyn, Bruce; Yeh, Chyon; Smith-Hall, Nancy

2007-01-01

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day. PMID:18080055

Why has the Universal Coverage Scheme in Thailand achieved a pro-poor public subsidy for health care?

PubMed Central

2012-01-01

Background Thailand has achieved universal health coverage since 2002 through the implementation of the Universal Coverage Scheme (UCS) for 47 million of the population who were neither private sector employees nor government employees. A well performing UCS should achieve health equity goals in terms of health service use and distribution of government subsidy on health. With these goals in mind, this paper assesses the magnitude and trend of government health budget benefiting the poor as compared to the rich UCS members. Method Benefit incidence analysis was conducted using the nationally representative household surveys, Health and Welfare Surveys, between 2003 and 2009. UCS members are grouped into five different socio-economic status using asset indexes and wealth quintiles. Findings The total government subsidy, net of direct household payment, for combined outpatient (OP) and inpatient (IP) services to public hospitals and health facilities provided to UCS members, had increased from 30 billion Baht (US$ 1 billion) in 2003 to 40-46 billion Baht in 2004-2009. In 2003 for 23% and 12% of the UCS members who belonged to the poorest and richest quintiles of the whole-country populations respectively, the share of public subsidies for OP service was 28% and 7% for the poorest and the richest quintiles, whereby for IP services the share was 27% and 6% for the poorest and richest quintiles respectively. This reflects a pro-poor outcome of public subsidies to healthcare. The OP and IP public subsidies remained consistently pro-poor in subsequent years. The pro-poor benefit incidence is determined by higher utilization by the poorest than the richest quintiles, especially at health centres and district hospitals. Thus the probability and the amount of household direct health payment for public facilities by the poorest UCS members were less than their richest counterparts. Conclusions Higher utilization and better financial risk protection benefiting the poor UCS members are the results of extensive geographical coverage of health service infrastructure especially at district level, adequate finance and functioning primary healthcare, comprehensive benefit package and zero copayment at points of services. PMID:22992431

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model

PubMed Central

Huang, Tzou-Chi; Tsai, Shinn-Shyong; Liu, Li-Fang; Liu, Yu Lin; Liu, Hung-Jen; Chuang, Kuo Pin

2010-01-01

AIM: To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). METHODS: BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in colonic sections were detected by immunohistochemistry. RESULTS: There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-α were also decreased in AL-treated groups. CONCLUSION: We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC. PMID:20806438

Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

PubMed Central

Fite, Alemu; Furrie, Elizabeth; Bahrami, Bahram; Cummings, John H.; Steinke, Douglas T.; Macfarlane, George T.

2013-01-01

Bacteria belonging to the normal colonic microbiota are associated with the etiology of ulcerative colitis (UC). Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown. The aim of this investigation was to characterize mucosal biofilm communities over time and to determine the relationship of these bacteria to patient age and disease severity and duration. Multiple rectal biopsy specimens were taken from 33 patients with active UC over a period of 1 year. Real-time PCR was used to quantify mucosal bacteria in UC patients compared to 18 noninflammatory bowel disease controls, and the relationship between indicators of disease severity and bacterial colonization was evaluated by linear regression analysis. Significant differences were detected in bacterial populations on the UC mucosa and in the control group, which varied over the study period. High clinical activity indices (CAI) and sigmoidoscopy scores (SS) were associated with enterobacteria, desulfovibrios, type E Clostridium perfringens, and Enterococcus faecalis, whereas the reverse was true for Clostridium butyricum, Ruminococcus albus, and Eubacterium rectale. Lactobacillus and bifidobacterium numbers were linked with low CAI. Only E. rectale and Clostridium clostridioforme had a high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in UC and that bacterial community structure is related to disease severity. PMID:23269735

The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

PubMed

Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

2017-05-01

To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin <100 μg/g) were included for cross-sectional analysis. Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

The Impact of Medicaid Disproportionate Share Hospital Payment on Provision of Hospital Uncompensated Care

PubMed Central

Hsieh, Hui-Min; Bazzoli, Gloria J.

2012-01-01

This study examines the association between hospital uncompensated care (UC) and reductions in Medicaid Disproportionate Share Hospital (DSH) payments resulting from the 1997 Balanced Budget Act. Data on California hospitals from 1996 to 2003 were examined using two-stage least squares with a first-differencing model to control for potential feedback effects. Our findings suggest that not-for-profit hospitals did reduce UC provision in response to reductions in Medicaid DSH, but the response was inelastic in value. Policy makers need to continue to monitor how UC changes as sources of support for indigent care change with the Patient Protection and Affordable Care Act (PPACA). PMID:23230705

Theoretical Model for Volume Fraction of UC, 235U Enrichment, and Effective Density of Final U 10Mo Alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devaraj, Arun; Prabhakaran, Ramprashad; Joshi, Vineet V.

2016-04-12

The purpose of this document is to provide a theoretical framework for (1) estimating uranium carbide (UC) volume fraction in a final alloy of uranium with 10 weight percent molybdenum (U-10Mo) as a function of final alloy carbon concentration, and (2) estimating effective 235U enrichment in the U-10Mo matrix after accounting for loss of 235U in forming UC. This report will also serve as a theoretical baseline for effective density of as-cast low-enriched U-10Mo alloy. Therefore, this report will serve as the baseline for quality control of final alloy carbon content

Radial Symmetry of p-Harmonic Minimizers

NASA Astrophysics Data System (ADS)

Koski, Aleksis; Onninen, Jani

2018-03-01

"It is still not known if the radial cavitating minimizers obtained by uc(Ball) (Philos Trans R Soc Lond A 306:557-611, 1982) (and subsequently by many others) are global minimizers of any physically reasonable nonlinearly elastic energy". This quotation is from uc(Sivaloganathan) and uc(Spector) (Ann Inst Henri Poincaré Anal Non Linéaire 25(1):201-213, 2008) and seems to be still accurate. The model case of the p-harmonic energy is considered here. We prove that the planar radial minimizers are indeed the global minimizers provided we prescribe the admissible deformations on the boundary. In the traction free setting, however, even the identity map need not be a global minimizer.

An empirical comparison of Markov cohort modeling and discrete event simulation in a capacity-constrained health care setting.

PubMed

Standfield, L B; Comans, T A; Scuffham, P A

2017-01-01

To empirically compare Markov cohort modeling (MM) and discrete event simulation (DES) with and without dynamic queuing (DQ) for cost-effectiveness (CE) analysis of a novel method of health services delivery where capacity constraints predominate. A common data-set comparing usual orthopedic care (UC) to an orthopedic physiotherapy screening clinic and multidisciplinary treatment service (OPSC) was used to develop a MM and a DES without (DES-no-DQ) and with DQ (DES-DQ). Model results were then compared in detail. The MM predicted an incremental CE ratio (ICER) of $495 per additional quality-adjusted life-year (QALY) for OPSC over UC. The DES-no-DQ showed OPSC dominating UC; the DES-DQ generated an ICER of $2342 per QALY. The MM and DES-no-DQ ICER estimates differed due to the MM having implicit delays built into its structure as a result of having fixed cycle lengths, which are not a feature of DES. The non-DQ models assume that queues are at a steady state. Conversely, queues in the DES-DQ develop flexibly with supply and demand for resources, in this case, leading to different estimates of resource use and CE. The choice of MM or DES (with or without DQ) would not alter the reimbursement of OPSC as it was highly cost-effective compared to UC in all analyses. However, the modeling method may influence decisions where ICERs are closer to the CE acceptability threshold, or where capacity constraints and DQ are important features of the system. In these cases, DES-DQ would be the preferred modeling technique to avoid incorrect resource allocation decisions.

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

PubMed

Osterman, Mark T; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D

2014-11-01

Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 μg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 μg/g. Secondary outcomes were continued remission with FC <100 μg/g or <200 μg/g (among patients with pre-randomization values above these levels). The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 μg/g (P = .04) and 200 μg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 μg/g compared with those with FC <200 μg/g (P = .01). Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Extracellular superoxide dismutase increased the therapeutic potential of human mesenchymal stromal cells in radiation pulmonary fibrosis.

PubMed

Wei, Li; Zhang, Jing; Yang, Zai-Liang; You, Hua

2017-05-01

Pulmonary fibrosis induced by irradiation is a significant problem of radiotherapy in cancer patients. Extracellular superoxide dismutase (SOD3) is found to be predominantly and highly expressed in the extracellular matrix of lung and plays a pivotal role against oxidative damage. Early administration of mesenchymal stromal cells (MSCs) has been demonstrated to reduce fibrosis of damaged lung. However, injection of MSCs at a later stage would be involved in fibrosis development. The present study aimed to determine whether injection of human umbilical cord-derived MSCs (UC-MSCs) over-expressing SOD3 at the established fibrosis stage would have beneficial effects in a mice model of radiation pulmonary fibrosis. Herein, pulmonary fibrosis in mice was induced using Cobalt-60 ( 60 Co) irradiator with 20 Gy, followed by intravenous injection of UC-MSCs, transduced or not to express SOD3 at 2 h (early delivery) and 60 day (late delivery) post-irradiation, respectively. Our results demonstrated that the early administration of UC-MSCs could attenuate the microscopic damage, reduce collagen deposition, inhibit (myo)fibroblast proliferation, reduce inflammatory cell infiltration, protect alveolar type II (AE2) cell injury, prevent oxidative stress and increase antioxidant status, and reduce pro-fibrotic cytokine level in serum. Furthermore, the early treatment with SOD3-infected UC-MSCs resulted in better improvement. However, we failed to observe the therapeutic effects of UC-MSCs, transduced to express SOD3, during established fibrosis. Altogether, our results demonstrated that the early treatment with UC-MSCs alone significantly reduced radiation pulmonary fibrosis in mice through paracrine effects, with further improvement by administration of SOD3-infected UC-MSCs, suggesting that SOD3-infected UC-MSCs may be a potential cell-based gene therapy to treat clinical radiation pulmonary fibrosis. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Effect of Selective Inhibition of Reactivated Nicotine-Associated Memories With Propranolol on Nicotine Craving.

PubMed

Xue, Yan-Xue; Deng, Jia-Hui; Chen, Ya-Yun; Zhang, Li-Bo; Wu, Ping; Huang, Geng-Di; Luo, Yi-Xiao; Bao, Yan-Ping; Wang, Yu-Mei; Shaham, Yavin; Shi, Jie; Lu, Lin

2017-03-01

A relapse into nicotine addiction during abstinence often occurs after the reactivation of nicotine reward memories, either by acute exposure to nicotine (a smoking episode) or by smoking-associated conditioned stimuli (CS). Preclinical studies suggest that drug reward memories can undergo memory reconsolidation after being reactivated, during which they can be weakened or erased by pharmacological or behavioral manipulations. However, translational clinical studies using CS-induced memory retrieval-reconsolidation procedures to decrease drug craving reported inconsistent results. To develop and test an unconditioned stimulus (UCS)-induced retrieval-reconsolidation procedure to decrease nicotine craving among people who smoke. A translational rat study and human study in an academic outpatient medical center among 96 male smokers (aged 18- 45 years) to determine the association of propranolol administration within the time window of memory reconsolidation (after retrieval of the nicotine-associated memories by nicotine UCS exposure) with relapse to nicotine-conditioned place preference (CPP) and operant nicotine seeking in rats, and measures of preference to nicotine-associated CS and nicotine craving among people who smoke. The study rats were injected noncontingently with the UCS (nicotine 0.15 mg/kg, subcutaneous) in their home cage, and the human study participants administered a dose of propranolol (40 mg, per os; Zhongnuo Pharma). Nicotine CPP and operant nicotine seeking in rats, and preference and craving ratings for newly learned and preexisting real-life nicotine-associated CS among people who smoke. Sixty-nine male smokers completed the experiment and were included for statistical analysis: 24 in the group that received placebo plus 1 hour plus UCS, 23 who received propranolol plus 1 hour plus UCS, and 22 who received UCS plus 6 hours plus propranolol. In rat relapse models, propranolol injections administered immediately after nicotine UCS-induced memory retrieval inhibited subsequent nicotine CPP and operant nicotine seeking after short (CPP, d = 1.72, 95% CI, 0.63-2.77; operant seeking, d = 1.61, 95% CI, 0.59-2.60) or prolonged abstinence (CPP, d = 1.46, 95% CI, 0.42-2.47; operant seeking: d = 1.69, 95% CI, 0.66-2.69), as well as nicotine priming-induced reinstatement of nicotine CPP (d = 1.28, 95% CI, 0.27-2.26) and operant nicotine seeking (d = 1.61, 95% CI, 0.59-2.60) after extinction. Among the smokers, oral propranolol administered prior to nicotine UCS-induced memory retrieval decreased subsequent nicotine preference induced by newly learned nicotine CS (CS1, Cohen d = 0.61, 95% CI, 0.02-1.19 and CS2, d = 0.69, 95% CI, 0.10-1.28, respectively), preexisting nicotine CS (d = 0.57, 95% CI, -0.02 to 1.15), and nicotine priming (CS1, d = 0.82, 95% CI, 0.22-1.41 and CS2, d = 0.78, 95% CI, 0.18-1.37, respectively; preexisting nicotine CS, d = 0.92, 95% CI, 0.31-1.52), as well as nicotine craving induced by the preexisting nicotine CS (d = 0.64, 95% CI, 0.05-1.22), and nicotine priming (d = 1.15, 95% CI, 0.52-1.76). In rat-to-human translational study, a novel UCS-induced memory retrieval-reconsolidation interference procedure inhibited nicotine craving induced by exposure to diverse nicotine-associated CS and nicotine itself. This procedure should be studied further in clinical trials.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up

PubMed Central

van der Valk, Mirthe E.; Mangen, Marie-Josée J.; Severs, Mirjam; van der Have, Mike; Dijkstra, Gerard; van Bodegraven, Ad A.; Fidder, Herma H.; de Jong, Dirk J.; van der Woude, C. Janneke; Romberg-Camps, Mariëlle J. L.; Clemens, Cees H. M.; Jansen, Jeroen M.; van de Meeberg, Paul C.; Mahmmod, Nofel; van der Meulen-de Jong, Andrea E.; Ponsioen, Cyriel Y.; Bolwerk, Clemens; Vermeijden, J. Reinoud; Siersema, Peter D.; Leenders, Max; Oldenburg, Bas

2016-01-01

Background With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02–3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61–13.86)). Conclusions BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC. PMID:27099937

High-Throughput Multi-Analyte Luminex Profiling Implicates Eotaxin-1 in Ulcerative Colitis

PubMed Central

Coburn, Lori A.; Horst, Sara N.; Chaturvedi, Rupesh; Brown, Caroline T.; Allaman, Margaret M.; Scull, Brooks P.; Singh, Kshipra; Piazuelo, M. Blanca; Chitnavis, Maithili V.; Hodges, Mallary E.; Rosen, Michael J.; Williams, Christopher S.; Slaughter, James C.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.

2013-01-01

Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies. PMID:24367513

Osteocalcin is not a strong determinant of serum testosterone and sperm count in men from infertile couples.

PubMed

Schwetz, V; Gumpold, R; Graupp, M; Hacker, N; Schweighofer, N; Trummer, O; Pieber, T R; Ballon, M; Lerchbaum, E; Obermayer-Pietsch, B

2013-07-01

Osteocalcin (OC) - released by osteoblasts and known as a marker of bone turnover - has been suggested to influence male fertility in murine models by enhancing testosterone production and sperm count. Results from clinical studies are scarce, however. The aim of this cross-sectional study was to investigate the proposed association of OC, undercarboxylated osteocalcin (ucOC) or carboxylated osteocalcin (cOC) with testosterone and sperm count in a cohort of 159 young male adults from infertile couples. Semen analysis was performed. Testosterone, free testosterone, LH, OC and ucOC were measured in serum samples after an overnight fast. cOC and OC correlated weakly but significantly with testosterone (OC: r = 0.165, p = 0.040, cOC: r = 0.193, p = 0.017), but not after adjusting for age and body mass index (BMI) or waist-hip ratio (WHR). %ucOC (ucOC levels expressed as percentage of total OC) correlated inversely with LH (r = -0.184, p = 0.023) and remained significant after the same adjustment. No significant correlations were observed between OC, cOC, ucOC, %ucOC and sperm count, semen volume and number of vital spermatozoa. In binary logistic regression analyses, none of the parameters of OC were predictors of oligozoospermia after adjusting for age and BMI or WHR. The weak association between %ucOC and LH has marginal clinical importance because of the lack of associations of parameters of OC with testosterone and sperm count. The current data thus cannot support the notion that OC is associated with male fertility in young men from infertile couples. © 2013 American Society of Andrology and European Academy of Andrology.

Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis

PubMed Central

Lin, Xue; Chang, Ying; Liu, Jing; Zhou, Rui; Nie, Jia-Yan; Dong, Wei-Guo; Zhao, Qiu; Li, Jin

2017-01-01

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines. PMID:29228739

Long-Term Use of Supplemental Vitamins and Minerals Does Not Reduce the Risk of Urothelial Cell Carcinoma of the Bladder in the VITamins And Lifestyle Study

PubMed Central

Hotaling, James M.; Wright, Jonathan L.; Pocobelli, Gaia; Bhatti, Parveen; Porter, Michael P.; White, Emily

2011-01-01

Purpose Urothelial Carcinoma (UC) has the highest lifetime treatment cost of any cancer making it an ideal target for preventative therapies. Previous work has suggested that certain vitamin and mineral supplements may reduce the risk of UC. We sought to use the prospective VITamins And Lifestyle (VITAL) cohort to examine the association of all commonly taken vitamin and mineral supplements as well as 6 common anti-inflammatory supplements with incident UC in a United States population. Materials&Methods 77,050 eligible VITAL participants completed a detailed questionnaire at baseline on supplement use and cancer risk factors. . After 6 years of follow-up, 330 incident UC cases occurring in the cohort were identified via linkage to the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry. We analyzed use of supplemental vitamins (multivitamins, beta-carotene, retinol, folic acid, vitamins B1, B3, B6, B12, C, D and E), minerals (calcium, iron, magnesium, zinc, and selenium), and anti-inflammatory supplements (glucosamine, chondroitin, saw-palmetto, ginko-biloba, fish oil and garlic). For each supplement, the hazard ratios (risk ratios) for UC comparing each category of users to nonusers, and 95% confidence intervals, were determined using Cox proportional hazards regression., adjusted for potential confounders. Results None of the vitamin, mineral or anti-inflammatory supplements was significantly associated with UC risk in either age-adjusted or multivariate models. Conclusions The results of this study do not support the use of commonly taken vitamin or mineral supplements or 6 common anti-inflammatory supplements for chemoprevention of UC. PMID:21334017

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

PubMed

Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

2016-10-01

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for TTR ≥ 70 % compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79 % of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

PubMed

Bagi, C M; Berryman, E R; Teo, S; Lane, N E

2017-12-01

The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Ulcerative colitis in northern Portugal and Galicia in Spain.

PubMed

Barreiro-de Acosta, Manuel; Magro, Fernando; Carpio, Daniel; Lago, Paula; Echarri, Ana; Cotter, José; Pereira, Santos; Gonçalves, Raquel; Lorenzo, Aurelio; Carvalho, Laura; Castro, Javier; Barros, Luisa; Dias, Jorge Amil; Rodrigues, Susana; Portela, Francisco; Dias, Camila; da Costa-Pereira, Altamiro

2010-07-01

Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC. A cross-sectional study was conducted during a 15-month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken. A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846-4.058; OR 5.799, 95% CI: 3.433-9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641-15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries. In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease.

Randomized noninferiority trial of telephone versus in-person genetic counseling for hereditary breast and ovarian cancer.

PubMed

Schwartz, Marc D; Valdimarsdottir, Heiddis B; Peshkin, Beth N; Mandelblatt, Jeanne; Nusbaum, Rachel; Huang, An-Tsun; Chang, Yaojen; Graves, Kristi; Isaacs, Claudine; Wood, Marie; McKinnon, Wendy; Garber, Judy; McCormick, Shelley; Kinney, Anita Y; Luta, George; Kelleher, Sarah; Leventhal, Kara-Grace; Vegella, Patti; Tong, Angie; King, Lesley

2014-03-01

Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery. Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC. TC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61), perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient. Genetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs.

Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice.

PubMed

Filho, Carlos Borges; Jesse, Cristiano Ricardo; Donato, Franciele; Del Fabbro, Lucian; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Giacomeli, Renata; Antunes, Michelle; Luchese, Cristiane; Roman, Silvane Souza; Boeira, Silvana Peterini

2016-11-15

Chrysin is a flavonoid which is found in bee propolis, honey and various plants. Antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. Conversely, neurochemical factors associated with this effect require further investigations. Thus, we investigated the possible involvement of pro-inflammatory cytokines, kynurenine pathway (KP), 5-hydroxytryptamine (5-HT) metabolism and caspases activities in the effect of chrysin in mice exposed to unpredictable chronic stress (UCS). UCS applied for 28 days induced a depressive-like behavior, characterized by decrease in the time of grooming in the splash test and by increase in the immobility time in the tail suspension test. Oral treatment with chrysin (5 or 20mg/kg, 28 days), similarly to fluoxetine (10mg/kg, positive control), culminated in the prevention of these alterations. UCS elevated plasma levels of corticotropin-releasing hormone and adrenocorticotropic hormone, as well the tumor necrosis factor-α, interleukin-1β, interleukin-6 and kynurenine levels in the prefrontal cortex (PFC) and hippocampus (HP). UCS induced the decrease in the 5-HT levels in the HP and the increase in the indoleamine-2,3-dioxygenase, caspase 3 and 9 activities in the PFC and HP. Treatment with chrysin, similarly to fluoxetine, promoted the attenuation of these alterations occasioned by UCS. These results corroborated with the antidepressant potential of chrysin in the treatment of psychiatric diseases. Furthermore, this work indicated the association of pro-inflammatory cytokines synthesis, KP, 5-HT metabolism and caspases activities with the action exercised by chrysin in mice exposed to UCS. Copyright © 2016 Elsevier B.V. All rights reserved.

Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

PubMed

Mijwel, Sara; Cardinale, Daniele A; Norrbom, Jessica; Chapman, Mark; Ivarsson, Niklas; Wengström, Yvonne; Sundberg, Carl Johan; Rundqvist, Helene

2018-05-11

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

PubMed Central

Zhou, Hai-xiao; Liu, Zhi-gang; Liu, Xiao-jiao; Chen, Qian-xue

2016-01-01

Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions. PMID:26981097

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

PubMed

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

Former University of California Chancellors Urge New Funding Models for UC. Research & Occasional Paper Series: CSHE.15.11

ERIC Educational Resources Information Center

Center for Studies in Higher Education, 2011

2011-01-01

In this era of massive budget cuts, the survival of the University of California as a great institution of learning has become the subject of increasingly urgent debate. Twenty-two of the twenty-nine living former UC chancellors met in San Francisco on June 26-28, 2011 to discuss the current threats facing the University and all of California…

Muon Collider 2011

Science.gov Websites

Organization Registration Program Working Groups Poster Session Venue Transportation Accommodations Social Events Visas Telluride Poster Sponsors Participants Co-Chairs: Marco Battaglia (LBNL, UC Santa Cruz

Effect of an extract based on the medicinal mushroom Agaricus blazei Murill on expression of cytokines and calprotectin in patients with ulcerative colitis and Crohn's disease.

PubMed

Førland, D T; Johnson, E; Saetre, L; Lyberg, T; Lygren, I; Hetland, G

2011-01-01

An immunomodulatory extract (AndoSan™) based on the medicinal mushroom Agaricus blazei Murill (AbM) has shown to reduce blood cytokine levels in healthy volunteers after 12 days' ingestion, pointing to an anti-inflammatory effect. The aim was to study whether AndoSan™ had similar effects on cytokines in patients with ulcerative colitis (UC) and Crohn's disease (CD). Calprotectin, a marker for inflammatory bowel disease (IBD), was also measured. Patients with CD (n = 11) and with UC (n = 10) consumed 60 ml/day of AndoSan™. Patient blood plasma was harvested before and after 6 h LPS (1 ng/ml) stimulation ex vivo. Plasma and faecal calprotectin levels were analysed using ELISA and 17 cytokines [IL-2, IFN-γ, IL-12 (Th1), IL-4, IL-5, IL-13 (Th2), IL-7, IL-17, IL-1β, IL-6, TNF-α, IL-8, MIP-1β, MCP-1, G-CSF, GM-CSF and IL-10] by multiplex assay. After 12 days' ingestion of AndoSan™, baseline plasma cytokine levels in UC was reduced for MCP-1 (40%) and in LPS-stimulated blood for MIP-1β (78%), IL-6 (44%), IL-1β (41%), IL-8 (30%), G-CSF (29%), MCP-1 (18%) and GM-CSF (17%). There were corresponding reductions in CD: IL-2 (100%), IL-17 (55%) and IL-8 (29%) and for IL-1β (35%), MIP-1β (30%), MCP-1 (22%), IL-8 (18%), IL-17 (17%) and G-CSF (14%), respectively. Baseline concentrations for the 17 cytokines in the UC and CD patient groups were largely similar. Faecal calprotectin was reduced in the UC group. Ingestion of an AbM-based medicinal mushroom by patients with IBD resulted in interesting anti-inflammatory effects as demonstrated by declined levels of pathogenic cytokines in blood and calprotectin in faeces. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG).

PubMed

Eriksson, Carl; Marsal, Jan; Bergemalm, Daniel; Vigren, Lina; Björk, Jan; Eberhardson, Michael; Karling, Pontus; Söderman, Charlotte; Myrelid, Pär; Cao, Yang; Sjöberg, Daniel; Thörn, Mari; Karlén, Per; Hertervig, Erik; Strid, Hans; Ludvigsson, Jonas F; Almer, Sven; Halfvarson, Jonas

Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness. Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC). Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48). Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study.

PubMed

Harrigan, Maura; Cartmel, Brenda; Loftfield, Erikka; Sanft, Tara; Chagpar, Anees B; Zhou, Yang; Playdon, Mary; Li, Fangyong; Irwin, Melinda L

2016-03-01

Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers. One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months. The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05). Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care. © 2015 by American Society of Clinical Oncology.

Effect of DECIDE (Decision-making Education for Choices In Diabetes Everyday) Program Delivery Modalities on Clinical and Behavioral Outcomes in Urban African Americans With Type 2 Diabetes: A Randomized Trial.

PubMed

Fitzpatrick, Stephanie L; Golden, Sherita Hill; Stewart, Kerry; Sutherland, June; DeGross, Sharie; Brown, Tina; Wang, Nae-Yuh; Allen, Jerilyn; Cooper, Lisa A; Hill-Briggs, Felicia

2016-12-01

To compare the effectiveness of three delivery modalities of Decision-making Education for Choices In Diabetes Everyday (DECIDE), a nine-module, literacy-adapted diabetes and cardiovascular disease (CVD) education and problem-solving training, compared with an enhanced usual care (UC), on clinical and behavioral outcomes among urban African Americans with type 2 diabetes. Eligible participants (n = 182) had a suboptimal CVD risk factor profile (A1C, blood pressure, and/or lipids). Participants were randomized to DECIDE Self-Study (n = 46), DECIDE Individual (n = 45), DECIDE Group (n = 46), or Enhanced UC (n = 45). Intervention duration was 18-20 weeks. Outcomes were A1C, blood pressure, lipids, problem-solving, disease knowledge, and self-care activities, all measured at baseline, 1 week, and 6 months after completion of the intervention. DECIDE modalities and Enhanced UC did not significantly differ in clinical outcomes at 6 months postintervention. In participants with A1C ≥7.5% (58 mmol/mol) at baseline, A1C declined in each DECIDE modality at 1 week postintervention (P < 0.05) and only in Self-Study at 6 months postintervention (b = -0.24, P < 0.05). There was significant reduction in systolic blood pressure in Self-Study (b = -4.04) and Group (b = -3.59) at 6 months postintervention. Self-Study, Individual, and Enhanced UC had significant declines in LDL and Self-Study had an increase in HDL (b = 1.76, P < 0.05) at 6 months postintervention. Self-Study and Individual had a higher increase in knowledge than Enhanced UC (P < 0.05), and all arms improved in problem-solving (P < 0.01) at 6 months postintervention. DECIDE modalities showed benefits after intervention. Self-Study demonstrated robust improvements across clinical and behavioral outcomes, suggesting program suitability for broader dissemination to populations with similar educational and literacy levels. © 2016 by the American Diabetes Association.

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

PubMed

Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2007-06-01

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

Ultra-fast pump-probe determination of electron-phonon coupling in cuprate superconductors

NASA Astrophysics Data System (ADS)

Mihailovic, Dragan

2010-03-01

Fresh femtosecond spectroscopy experiments show the electron-phonon interaction strength λ to be 0.7 and 1.4 for YBCO and LSCO respectively and not around 0.2 as previously reported [1]. The revised estimates arise primarily from improved time-resolution, and also partly from improved modeling. Comparison with classical superconductors and pnictides shows non-monotonic correlation of λ with Tc. Systematic new measurements of the condensate vaporization energy (Uv) in cuprates [2] and pnictides reveals a power-law dependence on Tc with exponent 2. However, Uc is 16-18 times greater than the BCS condensation energy Uc, implying that a significant heat capacity of the ``bosonic glue.'' In contrast, charge-density wave systems with electronically driven ordering transitions have Uv˜Uc. The data suggest BCS and Eliashberg-based models to be inappropriate for describing the physics of high-temperature superconductors, and point towards polaron models which consider strong or intermediate λ.[4pt] [1] C.Gadermeier et al., arXiv:0902.1636[0pt] [2] P.Kusar et al., Phys. Rev. Lett. 101, 227001 (2008)

Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials.

PubMed

Schwartz, Ann V; Schafer, Anne L; Grey, Andrew; Vittinghoff, Eric; Palermo, Lisa; Lui, Li-Yung L; Wallace, Robert B; Cummings, Steven R; Black, Dennis M; Bauer, Douglas C; Reid, Ian R

2013-06-01

In rodent models, undercarboxylated osteocalcin (ucOC) acts as a hormone that promotes insulin sensitivity and secretion. If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes. We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N = 6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N = 7113) of zoledronic acid (3 years), and Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N = 7076) of denosumab (3 years). Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM in all participants. Weight was measured annually in all trials. Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose. Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant: -0.47 mg/dL in FIT, 0.20 mg/dL in HORIZON-PFT, and 0.09 mg/dL in FREEDOM, all p > 0.6. Weight change differed between treatment and placebo groups in FIT (0.32 kg, p = 0.003) and FREEDOM (0.31 kg, p = 0.023) but not in HORIZON-PFT (0.15 kg, p = 0.132). In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively. Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (pooled relative risk [RR] = 0.90; 95% confidence interval [CI] 0.74-1.10). Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight, or diabetes risk in postmenopausal women. Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans. Copyright © 2013 American Society for Bone and Mineral Research.

Respiratory Tract Infections in Patients With Inflammatory Bowel Disease: Safety Analyses From Vedolizumab Clinical Trials.

PubMed

Feagan, Brian G; Bhayat, Fatima; Khalid, Mona; Blake, Aimee; Travis, Simon P L

2018-05-17

Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab. Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled. Cox proportional hazards models were used to estimate the incidence of upper RTIs [URTIs] and lower RTIs [LRTIs] with adjustment for significant covariates. In the RCTs [n = 1731 patients], the incidence of URTIs was numerically higher in patients receiving vedolizumab compared with those receiving placebo, although this difference was not statistically significant (38.7 vs 33.0 patients per 100 patient-years; hazard ratio [HR] 1.12; 95% confidence interval [CI]: 0.83-1.51; p = 0.463). The rate of LRTIs, including pneumonia, was numerically lower in the vedolizumab versus the placebo group: this difference was not statistically significant (7.7 vs 8.5 per 100 patient-years [HR 0.85; 95% CI: 0.48-1.52; p = 0.585]). Both URTIs and LRTIs were more frequent in patients with CD compared with UC. Most RTIs in patients receiving vedolizumab were not serious and did not require treatment discontinuation. Vedolizumab therapy was not associated with an increased incidence of respiratory tract infection compared with placebo.

Efficacy and Safety of Beclomethasone Dipropionate versus 5-Aminosalicylic Acid in the Treatment of Ulcerative Colitis: A Systematic Review and Meta-Analysis

PubMed Central

Ma, Tao; Wang, ChunLi; Wang, Jun; You, ShengYi

2016-01-01

Background Ulcerative colitis (UC) is a chronic and remitting inflammatory disease that is characterized by chronic idiopathic inflammation of the colon and bloody diarrhea. Currently drug treatment is the main intervention for patients with mild to moderate UC. Mesalazine (5-ASA) and beclomethasone dipropionate (BDP) have been widely used for the treatment of UC and have yielded satisfactory results. This study compared the effectiveness of 5-ASA and BDP in the treatment of UC. Methods The PubMed, Medline, SinoMed, Embase, and Cochrane Librinary databases were searched for eligible studies. Data were extracted by two of the coauthors independently and were analyzed using RevMan statistical software, version 5.3. Weighted mean differences (WMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration’s Risk of Bias Tool was used to assess the risk of bias. Results Seven randomized controlled trials that compared BDP with 5-ASA in treating UC were identified as eligible. The methodological quality of the trials ranged from low to moderate. A pooled analysis of effectiveness based on the Disease Activity Index (DAI) or other assessment method after treatment revealed that in the treatment of UC, there are no obvious differences between BDP and 5-ASA in inducing remission and clinical improvement (OR = 0.76, 95% CI = 0.56–1.03, P = 0.08). The total numbers of adverse events associated with BDP and 5-ASA treatments for UC were similar (OR = 1.21, 95% CI = 0.71–2.09, P = 0.48). The safety profiles for these two drugs are good. According to subgroup-analysis, we found no obvious differences of clinical efficacy between BDP and 5-ASA no matter oral or enema administration was used in the treatment of UC. A sensitivity analysis demonstrated the stability of the pooled results. Conclusion During induction treatment of mild to moderate UC, there is no obvious difference between the two groups with respect to remission and clinical improvement. Given that the upper confidence limit for the OR barely exceeds 1.0 and that the p-value is close to 0.05 for this primary efficacy outcome as well as that the horizontal block lies to the left of the vertical line, it indicates that the clinical efficacy of BDP may be better than 5-ASA. However, taking into account that BDP has the risk of hypothalamic-pituitary-adrenal axis (HPA) suppression, 5-ASA has a potential advantage of safety in the treatment of mild to moderate UC. PMID:27501314

A preliminary exploration of the feasibility of offering men information about potential prostate cancer treatment options before they know their biopsy results.

PubMed

Zeliadt, Steven B; Hannon, Peggy A; Trivedi, Ranak B; Bonner, Laura M; Vu, Thuy T; Simons, Carol; Kimmie, Crystal A; Hu, Elaine Y; Zipperer, Chris; Lin, Daniel W

2013-02-06

A small pre-test study was conducted to ascertain potential harm and anxiety associated with distributing information about possible cancer treatment options at the time of biopsy, prior to knowledge about a definitive cancer diagnosis. Priming men about the availability of multiple options before they have a confirmed diagnosis may be an opportunity to engage patients in more informed decision-making. Men with an elevated PSA test or suspicious Digital Rectal Examination (DRE) who were referred to a urology clinic for a biopsy were randomized to receive either the clinic's usual care (UC) biopsy instruction sheet (n = 11) or a pre-biopsy educational (ED) packet containing the biopsy instruction sheet along with a booklet about the biopsy procedure and a prostate cancer treatment decision aid originally written for newly diagnosed men that described in detail possible treatment options (n = 18). A total of 62% of men who were approached agreed to be randomized, and 83% of the ED group confirmed they used the materials. Anxiety scores were similar for both groups while awaiting the biopsy procedure, with anxiety scores trending lower in the ED group: 41.2 on a prostate-specific anxiety instrument compared to 51.7 in the UC group (p = 0.13). ED participants reported better overall quality of life while awaiting biopsy compared to the UC group (76.4 vs. 48.5, p = 0.01). The small number of men in the ED group who went on to be diagnosed with cancer reported being better informed about the risks and side effects of each option compared to men diagnosed with cancer in the UC group (p = 0.07). In qualitative discussions, men generally reported they found the pre-biopsy materials to be helpful and indicated having information about possible treatment options reduced their anxiety. However, 2 of 18 men reported they did not want to think about treatment options until after they knew their biopsy results. In this small sample offering pre-biopsy education about potential treatment options was generally well received by patients, appeared to be beneficial to men who went on to be diagnosed, and did not appear to increase anxiety unnecessarily among those who had a negative biopsy.

Epidemiology of inflammatory bowel disease in racial and ethnic migrant groups

PubMed Central

Misra, Ravi; Faiz, Omar; Munkholm, Pia; Burisch, Johan; Arebi, Naila

2018-01-01

AIM To summarise the current literature and define patterns of disease in migrant and racial groups. METHODS A structured key word search in Ovid Medline and EMBASE was undertaken in accordance with PRISMA guidelines. Studies on incidence, prevalence and disease phenotype of migrants and races compared with indigenous groups were eligible for inclusion. RESULTS Thirty-three studies met the inclusion criteria. Individual studies showed significant differences in incidence, prevalence and disease phenotype between migrants or race and indigenous groups. Pooled analysis could only be undertaken for incidence studies on South Asians where there was significant heterogeneity between the studies [95% for ulcerative colitis (UC), 83% for Crohn’s disease (CD)]. The difference between incidence rates was not significant with a rate ratio South Asian: Caucasian of 0.78 (95%CI: 0.22-2.78) for CD and 1.39 (95%CI: 0.84-2.32) for UC. South Asians showed consistently higher incidence and more extensive UC than the indigenous population in five countries. A similar pattern was observed for Hispanics in the United States. Bangladeshis and African Americans showed an increased risk of CD with perianal disease. CONCLUSION This review suggests that migration and race influence the risk of developing inflammatory bowel disease. This may be due to different inherent responses upon exposure to an environmental trigger in the adopted country. Further prospective studies on homogenous migrant populations are needed to validate these observations, with a parallel arm for in-depth investigation of putative drivers. PMID:29391765

Mental Health Does Not Moderate Compensatory Cognitive Training Efficacy for Veterans With a History of Mild Traumatic Brain Injury.

PubMed

Pagulayan, Kathleen F; O'Neil, Maya; Williams, Rhonda M; Turner, Aaron P; Golshan, Shahrokh; Roost, Mai S; Laman-Maharg, Benjamin; Huckans, Marilyn; Storzbach, Daniel; Twamley, Elizabeth W

2017-09-01

To examine the potential moderating effects of mental health symptoms on the efficacy of compensatory cognitive training (CCT) for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans with a history of mild traumatic brain injury (mTBI). Secondary analysis of a randomized controlled trial of CCT. Posttraumatic stress disorder, depression, and substance dependence symptom severity were examined as potential moderators of CCT efficacy for subjective cognitive complaints, use of cognitive strategies, and objective neurocognitive performance. Three Veterans Affairs medical centers. Participants included veterans with history of mTBI (N=119): 50 participated in CCT and 69 received usual care (UC). CCT is a 10-week group-based (90 minutes per session) manualized cognitive rehabilitation intervention. Objective (neuropsychological functioning) and subjective (self-report) cognitive functioning and use of cognitive strategies. Baseline mental health symptoms did not moderate CCT efficacy: veterans who received CCT reported significantly greater improvement in cognitive difficulties and use of cognitive strategies compared with the UC group, regardless of baseline mental health symptom severity. The CCT group also demonstrated significant improvements on neuropsychological measures of attention, learning, and executive functioning compared with the UC group, regardless of baseline mental health symptom severity. CCT is efficacious for improving objective cognitive functioning and compensatory strategy use for veterans with a history of mTBI, regardless of the severity of comorbid psychiatric symptoms. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Epidemiology of inflammatory bowel disease in racial and ethnic migrant groups.

PubMed

Misra, Ravi; Faiz, Omar; Munkholm, Pia; Burisch, Johan; Arebi, Naila

2018-01-21

To summarise the current literature and define patterns of disease in migrant and racial groups. A structured key word search in Ovid Medline and EMBASE was undertaken in accordance with PRISMA guidelines. Studies on incidence, prevalence and disease phenotype of migrants and races compared with indigenous groups were eligible for inclusion. Thirty-three studies met the inclusion criteria. Individual studies showed significant differences in incidence, prevalence and disease phenotype between migrants or race and indigenous groups. Pooled analysis could only be undertaken for incidence studies on South Asians where there was significant heterogeneity between the studies [95% for ulcerative colitis (UC), 83% for Crohn's disease (CD)]. The difference between incidence rates was not significant with a rate ratio South Asian: Caucasian of 0.78 (95%CI: 0.22-2.78) for CD and 1.39 (95%CI: 0.84-2.32) for UC. South Asians showed consistently higher incidence and more extensive UC than the indigenous population in five countries. A similar pattern was observed for Hispanics in the United States. Bangladeshis and African Americans showed an increased risk of CD with perianal disease. This review suggests that migration and race influence the risk of developing inflammatory bowel disease. This may be due to different inherent responses upon exposure to an environmental trigger in the adopted country. Further prospective studies on homogenous migrant populations are needed to validate these observations, with a parallel arm for in-depth investigation of putative drivers.

[Impact of pharmaceutical intervention in preventing relapses in depression in Primary Care].

PubMed

Rubio-Valera, María; Peñarrubia-María, M Teresa; Fernández-Vergel, Rita; Carvajal Tejadillo, Andrea Cecilia; Fernández Sánchez, Ana; Aznar-Lou, Ignacio; March-Pujol, Marian; Serrano-Blanco, Antoni

2016-05-01

To evaluate the long-term impact of a brief pharmacist intervention (PI) compared with usual care (UC) on prevention of depression relapse. randomised controlled clinical trial Primary Care Of the 179 depressed patients initiating antidepressants, the 113 whose clinical symptoms had remitted (main definition) at 6 months assessment were selected for this secondary study (PI=58; UC=55). PI was an interview to promote medication adherence when patients get antidepressants from pharmacy. Baseline, 3 months, and six-months follow-up assessments were made. The severity of depressive symptoms was evaluated with PHQ9. Patients presenting a remission of symptoms were selected. The patient medical records were reviewed to identify a relapse in the following 12 months by using 4 indicators. There was a lower proportion of patients that relapsed in the PI group than in the UC group 18 months after initiation of treatment, but the difference was not statistically significant either in the intent-to-treat analysis (OR=0.734 [95%CI; 0.273-1.975]) or the per-protocol analysis (OR=0.615 [95%CI; 0.183 -2.060]). All the sensitivity analyses showed consistent results. The sample size and adherence to the protocol in the intervention group were low. PI group showed a non-statistically significant tendency towards presenting fewer relapses. This could be related to the improvement in adherence among patients that received the intervention. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

PubMed Central

Shono, Akemi; Yoshida, Makiko; Yamana, Keiji; Thwin, Khin Kyae Mon; Kuroda, Jumpei; Kurokawa, Daisuke; Koda, Tsubasa; Nishida, Kosuke; Ikuta, Toshihiko; Mizobuchi, Masami; Taniguchi-Ikeda, Mariko

2017-01-01

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation. PMID:29138639

Structural and optical investigation in Er3+ doped Y2MoO6 phosphors

NASA Astrophysics Data System (ADS)

Mondal, Manisha; Rai, Vineet Kumar

2018-05-01

The Er3+ doped Y2MoO6 phosphors have been structurally and optically characterized by X-ray Diffraction (XRD), Field emission scanning electron microscopy (FESEM), UV-Vis absorption spectroscopy and frequency upconversion (UC) emission studies. The crystal and the particles size are found to be ˜ 85 nm and ˜ 200 nm from XRD and FESEM analysis. The intense peak at ˜ 206 nm in the UV-Vis absorption spectroscopy is attributed due to the charge transfer transition between the Mo6+ and the O2- ions in the MoO4 group in the host molybdate. The frequency UC emission studies of the prepared phosphors under 980 nm diode laser excitation shows the intense UC emission in the 0.3 mol% concentrations for the Er3+ ions. In the UC emission spectra, the emission peaks at green (˜ 525 nm and ˜ 546 nm) and red (˜ 656 nm) bands are corresponding to the 2H11/2, 4S3/2 → 4I15/2 and 4F9/2 → 4I15/2 transitions of Er3+ ions. The mechanisms involved in the UC process have been explored with the help of energy level diagram. Moreover, the CIE point (0.31, 0.60) lie in the green colour region which indicates that the developed phosphor have suitable applications in NIR to visible upconverter and in making green light display devices.

One-Year Effectiveness of a 3-Week Balneotherapy Program for the Treatment of Overweight or Obesity

PubMed Central

Hanh, Thierry; Serog, Patrick; Fauconnier, Jérôme; Batailler, Pierre; Mercier, Florence; Roques, Christian F.; Blin, Patrick

2012-01-01

Objective. To assess the one-year effectiveness on weight loss of a 3-week balneotherapy program (BT). Method. A Zelen double consent randomised controlled trial to compare one-year BMI loss between a 3-week BT program versus usual care (UC) for overweight or obese patients (BMI: 27–35 kg/m2), associated or not with a dietary motivational interview (DMI) during the follow-up, using a 2 × 2 factorial design. Main analysis was a per protocol analysis comparing patients attending BT to patients managed by UC, matched on sex, overweight or obese status, DMI randomisation and a propensity score to attend BT or to be managed by UC. Results. From the 257 patients who completed the follow-up, 70 patients of each group could be matched. Mean BMI loss was 1.91 kg/m2 [95%CI: 1.46; 2.35] for the BT patients and 0.20 kg/m2 [−0.24; 0.64] for the UC patients (P < 0.001), corresponding to a significant BT benefit of 1.71 kg/m2 [1.08; 2.33]. There was no significant effect of DMI and no interaction with BT or UC. No adverse reaction was observed for patients attending BT. Conclusion. A 3-week BT program provided a significant one-year benefit over the usual GP dietary advice for overweight and obese patients. PMID:23346190

Tablet-Based Intervention for Reducing Children's Preoperative Anxiety: A Pilot Study.

PubMed

Chow, Cheryl H T; Van Lieshout, Ryan J; Schmidt, Louis A; Buckley, Norman

To examine the feasibility, acceptability, and effects of a novel tablet-based application, Story-Telling Medicine (STM), in reducing children's preoperative anxiety. Children (N = 100) aged 7 to 13 years who were undergoing outpatient surgery were recruited from a local children's hospital. This study comprised 3 waves: Waves 1 (n = 30) and 2 (n = 30) examined feasibility, and Wave 3 (n = 40) examined the acceptability of STM and compared its effect on preoperative anxiety to Usual Care (UC). In Wave 3, children were randomly allocated to receive STM+UC or UC. A change in preoperative anxiety was measured using the Children's Perioperative Multidimensional Anxiety Scale (CPMAS) 7 to 14 days before surgery (T1), on the day of surgery (T2), and 1 month postoperatively (T3). Wave 1 demonstrated the feasibility of participant recruitment and data collection procedures but identified challenges with attrition at T2 and T3. Wave 2 piloted a modified protocol that addressed attrition and increased the feasibility of follow-up. In Wave 3, children in the STM+UC demonstrated greater reductions in CPMAS compared with the UC group (ΔM = 119.90, SE = 46.36, t(27) = 2.59, p = .015; 95% confidence interval = 24.78-215.02). This pilot study provides preliminary evidence that STM is a feasible and acceptable intervention for reducing children's preoperative anxiety in a busy pediatric operative setting and supports the investigation of a full-scale randomized controlled trial.

Characterization of IBS-like symptoms in patients with ulcerative colitis in clinical remission.

PubMed

Jonefjäll, B; Strid, H; Ohman, L; Svedlund, J; Bergstedt, A; Simren, M

2013-09-01

Gastrointestinal symptoms compatible with Irritable Bowel Syndrome (IBS) are common in patients with inflammatory bowel disease. It has been suggested that these symptoms are a reflection of occult inflammation rather than coexisting IBS. The aim of this study was to characterize IBS-like symptoms in patients with Ulcerative Colitis (UC) in clinical remission by assessing inflammatory markers, psychological symptoms, and quality of life. Ninety-four patients with new onset of UC were followed prospectively during 3 years with yearly follow-up visits. The patients completed self-administrated questionnaires. Fecal calprotectin was used as an inflammatory biomarker. Remission was defined as a total Mayo-score ≤2 and an endoscopic subscore ≤1, with no relapse during the 3-month period prior to visit. The prevalence of patients that fulfilled Rome II criteria for IBS among UC patients in remission was 11% at visit 1, 23% at visit 2, and 17% at visit 3. When comparing UC patients in remission with and without IBS-like symptom, patients with IBS-like symptoms had more severe gastrointestinal symptoms, tendencies toward more severe psychological symptoms and reduced levels of quality of life, but the calprotectin levels did not differ between the two groups. IBS-like symptoms are common in patients with UC in clinical remission and these fluctuate over time. The symptoms are associated with poor psychological well-being and reduced quality of life, and do not seem to be a reflection of low-grade inflammatory activity. © 2013 John Wiley & Sons Ltd.

Upper-body progressive resistance training improves strength and household physical activity performance in women attending cardiac rehabilitation.

PubMed

Coke, Lola A; Staffileno, Beth A; Braun, Lynne T; Gulanick, Meg

2008-01-01

The purpose of this study was to examine the impact of moderate-intensity, progressive, upper-body resistance training (RT) on muscle strength and perceived performance of household physical activities (HPA) among women in cardiac rehabilitation. The 10-week, pretest-posttest, experiment randomized women to either usual care (UC) aerobic exercise or RT. Muscle strength for 5 upper-body RT exercises (chest press, shoulder press, biceps curl, lateral row, and triceps extension) was measured using the 1-Repetition Maximum Assessment. The RT group progressively increased weight lifted using 40%, 50%, and 60% of obtained 1-Repetition Maximum Assessment at 3-week intervals. Perceived performance of HPA was measured with the Kimble Household Activities Scale. The RT group (n = 16, mean age 64 +/- 11) significantly increased muscle strength in all 5 exercises in comparison with the UC group (n = 14, mean age 65 +/- 10) (chest press, 18% vs 11%; shoulder press, 24% vs 14%; biceps curl, 21% vs 12%; lateral row, 32% vs 9%; and triceps extension, 28% vs 20%, respectively). By study end, Household Activities Scale scores significantly increased (F = 13.878, P = .001) in the RT group (8.75 +/- 3.19 vs 11.25 +/- 2.14), whereas scores in the UC group decreased (8.60 +/- 3.11 vs 6.86 +/- 4.13). Progressive upper-body RT in women shows promise as an effective tool to increase muscle strength and improve the ability to perform HPA after a cardiac event. Beginning RT early after a cardiac event in a monitored cardiac rehabilitation environment can maximize the strengthening benefit.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

PubMed

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis

PubMed Central

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83–2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59–2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76–2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction. PMID:28182725

Cisplatin- Versus Non-Cisplatin-based First-Line Chemotherapy for Advanced Urothelial Carcinoma Previously Treated With Perioperative Cisplatin.

PubMed

Locke, Jennifer A; Pond, Gregory Russell; Sonpavde, Guru; Necchi, Andrea; Giannatempo, Patrizia; Paluri, Ravi Kumar; Niegisch, Guenter; Albers, Peter; Buonerba, Carlo; Di Lorenzo, Giuseppe; Vaishampayan, Ulka N; North, Scott A; Agarwal, Neeraj; Hussain, Syed A; Pal, Sumanta; Eigl, Bernhard J

2016-08-01

The optimal choice of first-line chemotherapy for patients with relapse of urothelial carcinoma (UC) after perioperative cisplatin-based chemotherapy (PCBC) is unclear. We investigated the outcomes with cisplatin rechallenge versus a non-cisplatin regimen in patients with recurrent metastatic UC after PCBC in a multicenter retrospective study. Individual patient-level data were collected for patients who had received various first-line chemotherapy regimens for advanced UC after previous PCBC. Cox proportional hazards models were used to investigate the prognostic ability of the type of perioperative and first-line chemotherapy to independently affect overall survival (OS) and progression-free survival (PFS) after accounting for known prognostic factors. Data were available for 145 patients (12 centers). The mean age was 62 years; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was > 0 for 42.0% of the patients. Of the 145 patients, 63% had received cisplatin-based first-line chemotherapy. The median time from previous chemotherapy (TFPC) was 6.2 months (range, 1-154 months). The median OS was 22 months (95% confidence interval [CI], 18-27 months), and the median PFS was 6 months (95% CI, 5-7 months). A better ECOG PS and a longer TFPC (> 12 months vs. ≤ 12 months; hazard ratio [HR], 0.32; 95% CI, 0.20-0.52; P < .001) was prognostic for OS and PFS. Cisplatin-based chemotherapy was associated with poor OS (HR, 1.86; 95% CI, 1.13-3.06; P = .015), which appeared to be pronounced in those patients with a TFPC of ≤ 12 months. Retreatment with cisplatin in the first-line setting was associated with worse OS (HR, 3.38; P < .001). The results of the present retrospective analysis suggest that for patients who have undergone previous PCBC for UC, rechallenging with cisplatin might confer a poorer OS, especially for those with progression within < 1 year. Copyright © 2015 Elsevier Inc. All rights reserved.

A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

PubMed

Langhorne, Peter; Wu, Olivia; Rodgers, Helen; Ashburn, Ann; Bernhardt, Julie

2017-09-01

Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. The trial took place in 56 acute stroke units in five countries. We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. We recruited 2104 (UK, n  = 610; Australasia, n  = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p  < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; p  < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group ( n  = 480, 46%) had a favourable outcome than in the UC group ( n  = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; p  = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome. These results informed a new trial proposal [A Very Early Rehabilitation Trial - DOSE (AVERT-DOSE)] aiming to determine the optimal frequency and dose of EM. The trial is registered with the Australian New Zealand Clinical Trials Registry number ACTRN12606000185561, Current Controlled Trials ISRCTN98129255 and ISRCTN98129255. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 54. See the NIHR Journals Library website for further project information. Funding was also received from the National Health and Medical Research Council Australia, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, and the Stroke Association. In addition, National Health and Medical Research Council fellowship funding was provided to Julie Bernhardt (1058635), who also received fellowship funding from the Australia Research Council (0991086) and the National Heart Foundation (G04M1571). The Florey Institute of Neuroscience and Mental Health, which hosted the trial, acknowledges the support received from the Victorian Government via the Operational Infrastructure Support Scheme.

Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer.

PubMed

Poort, Hanneke; Verhagen, Constans A H H V M; Peters, Marlies E W J; Goedendorp, Martine M; Donders, A Rogier T; Hopman, Maria T E; Nijhuis-van der Sanden, Maria W G; Berends, Thea; Bleijenberg, Gijs; Knoop, Hans

2017-01-28

Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer. The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14 weeks), and at follow-up assessments (18 and 26 weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue), functional impairments (Sickness Impact Profile total score, EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning) and quality of life (EORTC-QLQ-C30 subscale QoL). Outcomes at 14 weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26 weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants. To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients. NTR3812 ; date of registration: 23/01/2013.

Successful affiliations: principles and practices.

PubMed

Rice, Ann Madden

2011-01-01

An affiliation can help a healthcare provider prepare for the challenges of healthcare reform, the rapidly changing landscapes of the commercial insurance industry, and the public's expectations about service and quality. UC Davis Medical Center, a 645-bed tertiary hospital in Sacramento, California, with many hospital-based clinics and a community-based group of primary care clinics, has developed a number of principles for affiliation. These principles are based on its experience in legal and financial affiliations with an academic practice group, with individual and small groups of primary care physicians, and with community hospitals around oncology services linked with U.C. Davis' National Cancer Institute-designated cancer center. This article offers a process for evaluating the appropriateness of an affiliation. The chances for a successful affiliation improve if each party has indicated the value it hopes to derive and how to measure that value, has communicated with all affected constituents, and has an agreed-upon method for resolving disputes.

Aldehyde dehydrogenase induction in arsenic-exposed rat bladder epithelium.

PubMed

Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin

2016-01-01

Arsenic is widely distributed in the environment. Many human cancers, including urothelial carcinoma (UC), show a dose-dependent relationship with arsenic exposure in the south-west coast of Taiwan (also known as the blackfoot disease (BFD) areas). However, the molecular mechanisms of arsenic-mediated UC carcinogenesis has not yet been defined. In vivo study, the rat bladder epithelium were exposed with arsenic for 48 h. The proteins were extracted from untreated and arsenic-treated rat bladder cells and utilized two-dimensional gel electrophoresis and mass spectrometry. Selected peptides were extracted from the gel and identified by quadrupole-time of flight (Q-TOF) Ultima-Micromass spectra. The significantly difference expression of proteins in arsenic-treated groups as compared with untreated groups was confirmed by immunohistochemistry (IHC) and western blotting. We found that thirteen proteins were down-regulated and nine proteins were up-regulated in arsenic-treated rat bladder cells when compared with untreated groups. The IHC and western blotting results confirmed that aldehyde dehydrogenase (ALDH) protein was up-regulated in arsenic-treated rat bladder epithelium. Expression of ALDH protein was significantly higher in UC patients from BFD areas than those from non-BFD areas using IHC (p=0.018). In conclusion, the ALDH protein expression could be used as molecular markers for arsenic-induced transformation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Effects of a tailored lifestyle self-management intervention (TALENT) study on weight reduction: a randomized controlled trial.

PubMed

Melchart, Dieter; Löw, Peter; Wühr, Erich; Kehl, Victoria; Weidenhammer, Wolfgang

2017-01-01

Overweight and obesity are globally increasing risk factors for diseases in the context of metabolic syndrome. A randomized controlled trial was conducted to investigate whether there are any existing differences between two lifestyle intervention strategies with respect to weight reduction after 1 year. A total of 166 subjects with a body mass index of 28-35 kg/m 2 were enrolled in this trial at seven study centers; 109 were randomly allocated to the intervention group (comprehensive lifestyle modification program: web-based Individual Health Management [IHM]) with 3-month reduction phase plus 9-month maintenance phase, and 57 were allocated to the control group (written information with advice for healthy food habits: usual care [UC]). Body weight, waist circumference, blood pressure, laboratory findings, and bioimpedance analysis used to determine body composition were measured at baseline and after 3, 6, 9, and 12 months. The primary outcome parameter was body weight at month 12 compared to baseline. With respect to baseline status there were no statistically significant differences between the groups. Based on the intent-to-treat population, body weight showed a mean decrease of 8.7 kg (SD 6.1) in the intervention group (IHM) and 4.2 kg (SD 5) in the control group (UC) at month 12. This statistically significant difference ( P <0.001) was confirmed by various sensitivity analyses. Body mass index, waist circumference, high-density lipid cholesterol, body fat, and the ratio of fat and body cell mass improved to a significantly higher degree in the IHM group. IHM proved to be superior to UC in weight reduction after 1 year. With a mean loss of about 10% of the baseline weight, a clinically high relevant risk reduction for cardio-metabolic diseases is achievable.

Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.

PubMed

Kevans, D; Tyler, A D; Holm, K; Jørgensen, K K; Vatn, M H; Karlsen, T H; Kaplan, G G; Eksteen, B; Gevers, D; Hov, J R; Silverberg, M S

2016-03-01

There is an unexplained association between ulcerative colitis [UC] and primary sclerosing cholangitis [PSC], with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC. UC patients with PSC [PSC-UC] and without PSC [UC] were identified from biobanks at Oslo University Hospital, Foothills Hospital Calgary and Mount Sinai Hospital Toronto. Microbial DNA was extracted from colonic tissue and sequencing performed of the V4 region of the 16S rRNA gene on Illumina MiSeq. Sequences were assigned to operational taxonomic units [OTUs] using Quantitative Insights Into Microbial Ecology [QIIME]. Microbial alpha diversity, beta diversity, and relative abundance were compared between PSC-UC and UC phenotypes. In all, 31 PSC-UC patients and 56 UC patients were included. Principal coordinate analysis [PCoA] demonstrated that city of sample collection was the strongest determinant of taxonomic profile. In the Oslo cohort, Chao 1 index was modestly decreased in PSC-UC compared with UC [p = 0.04] but did not differ significantly in the Calgary cohort. No clustering by PSC phenotype was observed using beta diversity measures. For multiple microbial genera there were nominally significant differences between UC and PSC-UC, but results were not robust to false-discovery rate correction. No strong PSC-specific microbial associations in UC patients consistent across different cohorts were identified. Recruitment centre had a strong effect on microbial composition. Future studies should include larger cohorts to increase power and the ability to control for confounding factors. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Approaches to improve the stability of the antiviral agent UC781 in aqueous solutions.

PubMed

Damian, Festo; Fabian, Judit; Friend, David R; Kiser, Patrick F

2010-08-30

In this work, we evaluated the chemical stability profiles of UC781 based solutions to identify excipients that stabilize the microbicidal agent UC781. When different antioxidants were added to UC781 in sulfobutylether-beta-cyclodextrin (SBE-beta-CD) solutions and subjected to a 50 degrees C stability study, it was observed that EDTA was a better stabilizing agent than sodium metabisulfite, glutathione or ascorbic acid. Some antioxidants accelerated the degradation of UC781, suggesting metal-catalyzed degradation of UC781. Furthermore, we observed substantial degradation of UC781 when stored in 1% Tween 80 and 1% DMSO solutions alone or in those with 10mM EDTA. On the other hand, improved stability of UC781 in the presence of 100 and 200mM of EDTA was observed in these solutions. The addition of both EDTA and citric acid in the stock solutions resulted in recovery of more than 60% of UC781 after 12 weeks. Generally, 10% SBE-beta-CD in the presence of EDTA and citric acid stabilized UC781 solutions: the amount of UC781 recovered approaching 95% after 12 weeks of storage at 40 degrees C. We also showed that the desulfuration reaction of the UC781 thioamide involves oxygen by running solution stability studies in deoxygenated media. Improved stability of UC781 in the present study indicates that the incorporation of EDTA, citric acid and SBE-beta-CD and the removal of oxygen in formulations of this drug will aid in increasing the stability of UC781 where solutions of the drug are required. Published by Elsevier B.V.

Empirical relations of rock properties of outcrop and core samples from the Northwest German Basin for geothermal drilling

NASA Astrophysics Data System (ADS)

Reyer, D.; Philipp, S. L.

2014-09-01

Information about geomechanical and physical rock properties, particularly uniaxial compressive strength (UCS), are needed for geomechanical model development and updating with logging-while-drilling methods to minimise costs and risks of the drilling process. The following parameters with importance at different stages of geothermal exploitation and drilling are presented for typical sedimentary and volcanic rocks of the Northwest German Basin (NWGB): physical (P wave velocities, porosity, and bulk and grain density) and geomechanical parameters (UCS, static Young's modulus, destruction work and indirect tensile strength both perpendicular and parallel to bedding) for 35 rock samples from quarries and 14 core samples of sandstones and carbonate rocks. With regression analyses (linear- and non-linear) empirical relations are developed to predict UCS values from all other parameters. Analyses focus on sedimentary rocks and were repeated separately for clastic rock samples or carbonate rock samples as well as for outcrop samples or core samples. Empirical relations have high statistical significance for Young's modulus, tensile strength and destruction work; for physical properties, there is a wider scatter of data and prediction of UCS is less precise. For most relations, properties of core samples plot within the scatter of outcrop samples and lie within the 90% prediction bands of developed regression functions. The results indicate the applicability of empirical relations that are based on outcrop data on questions related to drilling operations when the database contains a sufficient number of samples with varying rock properties. The presented equations may help to predict UCS values for sedimentary rocks at depth, and thus develop suitable geomechanical models for the adaptation of the drilling strategy on rock mechanical conditions in the NWGB.

The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study.

PubMed

Andersen, Vibeke; Ernst, Anja; Christensen, Jane; Østergaard, Mette; Jacobsen, Bent A; Tjønneland, Anne; Krarup, Henrik B; Vogel, Ulla

2010-05-28

Crohn's disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (HO-1/HMOX1) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas the pro-inflammatory interleukin 1 beta (IL-1 beta/IL1B) and anti-inflammatory interleukin 10 (IL-10/IL10) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the IL-1 beta, IL-10, and HO-1 genes, together with smoking, were associated with risk of CD and UC. Allele frequencies of the IL-1 beta T-31C (rs1143627), and IL-10 rs3024505, G-1082A (rs1800896), C-819T (rs1800871), and C-592A (rs1800872) and HO-1 A-413T (rs2071746) SNPs were assessed using a case-control design in a Danish cohort of 336 CD and 498 UC patients and 779 healthy controls. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by logistic regression models. Carriers of rs3024505, a marker polymorphism flanking the IL-10 gene, were at increased risk of CD (OR = 1.40, 95% CI: 1.06-1.85, P = 0.02) and UC (OR = 1.43, 95% CI: 1.12-1.82, P = 0.004) and, furthermore, with risk of a diagnosis of CD and UC at young age (OR = 1.47, 95% CI: 1.10-1.96) and OR = 1.35, 95% CI: 1.04-1.76), respectively). No association was found between the IL-1 beta, IL-10 G-1082A, C-819T, C-592A, and HO-1 gene polymorphisms and CD or UC. No consistent interactions between smoking status and CD or UC genotypes were demonstrated. The rs3024505 marker polymorphism flanking the IL-10 gene was significantly associated with risk of UC and CD, whereas no association was found between IL-1 beta or HO-1 gene polymorphisms and risk of CD and UC in this Danish study, suggesting that IL-10, but not IL-1 beta or HO-1, has a role in IBD etiology in this population.

The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study

PubMed Central

2010-01-01

Background Crohns disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (HO-1/HMOX1) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas the pro-inflammatory interleukin 1β (IL-1β/IL1B) and anti-inflammatory interleukin 10 (IL-10/IL10) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the IL-1β, IL-10, and HO-1 genes, together with smoking, were associated with risk of CD and UC. Methods Allele frequencies of the IL-1β T-31C (rs1143627), and IL-10 rs3024505, G-1082A (rs1800896), C-819T (rs1800871), and C-592A (rs1800872) and HO-1 A-413T (rs2071746) SNPs were assessed using a case-control design in a Danish cohort of 336 CD and 498 UC patients and 779 healthy controls. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by logistic regression models. Results Carriers of rs3024505, a marker polymorphism flanking the IL-10 gene, were at increased risk of CD (OR = 1.40, 95% CI: 1.06-1.85, P = 0.02) and UC (OR = 1.43, 95% CI: 1.12-1.82, P = 0.004) and, furthermore, with risk of a diagnosis of CD and UC at young age (OR = 1.47, 95% CI: 1.10-1.96) and OR = 1.35, 95% CI: 1.04-1.76), respectively). No association was found between the IL-1β, IL-10 G-1082A, C-819T, C-592A, and HO-1 gene polymorphisms and CD or UC. No consistent interactions between smoking status and CD or UC genotypes were demonstrated. Conclusions The rs3024505 marker polymorphism flanking the IL-10 gene was significantly associated with risk of UC and CD, whereas no association was found between IL-1β or HO-1 gene polymorphisms and risk of CD and UC in this Danish study, suggesting that IL-10, but not IL-1β or HO-1, has a role in IBD etiology in this population. PMID:20509889

Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study.

PubMed

Hicks, Lucy C; Huang, Juzheng; Kumar, Sacheen; Powles, Sam T; Orchard, Timothy R; Hanna, George B; Williams, Horace R T

2015-09-01

Distinguishing between the inflammatory bowel diseases [IBD], Crohn's disease [CD] and ulcerative colitis [UC], is important for determining management and prognosis. Selected ion flow tube mass spectrometry [SIFT-MS] may be used to analyse volatile organic compounds [VOCs] in exhaled breath: these may be altered in disease states, and distinguishing breath VOC profiles can be identified. The aim of this pilot study was to identify, quantify, and analyse VOCs present in the breath of IBD patients and controls, potentially providing insights into disease pathogenesis and complementing current diagnostic algorithms. SIFT-MS breath profiling of 56 individuals [20 UC, 18 CD, and 18 healthy controls] was undertaken. Multivariate analysis included principal components analysis and partial least squares discriminant analysis with orthogonal signal correction [OSC-PLS-DA]. Receiver operating characteristic [ROC] analysis was performed for each comparative analysis using statistically significant VOCs. OSC-PLS-DA modelling was able to distinguish both CD and UC from healthy controls and from one other with good sensitivity and specificity. ROC analysis using combinations of statistically significant VOCs [dimethyl sulphide, hydrogen sulphide, hydrogen cyanide, ammonia, butanal, and nonanal] gave integrated areas under the curve of 0.86 [CD vs healthy controls], 0.74 [UC vs healthy controls], and 0.83 [CD vs UC]. Exhaled breath VOC profiling was able to distinguish IBD patients from controls, as well as to separate UC from CD, using both multivariate and univariate statistical techniques. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Risk association between the NF-κB1 -94ins/delATTG promoter polymorphism and inflammatory bowel diseases: a meta-analysis.

PubMed

Liang, Meilan; Xu, Xinyu; Gong, Yaoyao; Tang, Yurong; Lin, Lin

2012-09-01

Extensive investigation of the NF-κB1 -94ins/delATTG promoter polymorphism for risk association with ulcerative colitis (UC) and Crohn's disease (CD) risk has yielded conflicting results. The objective of this meta-analysis was to evaluate the risk association between the NF-κB1 -94ins/delATTG promoter polymorphism and UC and CD. All eligible case-control studies of the association of NF-κB1 -94ins/delATTG promoter polymorphism with UC and CD were identified in the Pubmed and Embase databases. From these data, odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Meta-analysis was performed for alleles (D vs. W) and genotypes (DD + WD vs. WW, DD vs. WW + WD, DD vs. WW, WD vs. WW) in a fixed/random effects model. Nine case-control studies that included 4,447 cases (2,631 UC and 1,816 CD) and 2,195 controls were identified. Results indicated increased risk association of D allele carriers with UC (D vs. W: OR = 1.08, 95 % CI = 1.01-1.17, P = 0.03; DD vs. WW + WD: OR = 1.16, 95 % CI = 1.01-1.32, P = 0.04 and DD vs. WW: OR = 1.20, 95 % CI = 1.03-1.39, P = 0.02). No risk association was identified with CD. This meta-analysis indicated that the NF-κB1 -94ins/delATTG promoter polymorphism is a risk factor for UC but not CD.

UC Merced Center for Computational Biology Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colvin, Michael; Watanabe, Masakatsu

Final report for the UC Merced Center for Computational Biology. The Center for Computational Biology (CCB) was established to support multidisciplinary scientific research and academic programs in computational biology at the new University of California campus in Merced. In 2003, the growing gap between biology research and education was documented in a report from the National Academy of Sciences, Bio2010 Transforming Undergraduate Education for Future Research Biologists. We believed that a new type of biological sciences undergraduate and graduate programs that emphasized biological concepts and considered biology as an information science would have a dramatic impact in enabling the transformationmore » of biology. UC Merced as newest UC campus and the first new U.S. research university of the 21st century was ideally suited to adopt an alternate strategy - to create a new Biological Sciences majors and graduate group that incorporated the strong computational and mathematical vision articulated in the Bio2010 report. CCB aimed to leverage this strong commitment at UC Merced to develop a new educational program based on the principle of biology as a quantitative, model-driven science. Also we expected that the center would be enable the dissemination of computational biology course materials to other university and feeder institutions, and foster research projects that exemplify a mathematical and computations-based approach to the life sciences. As this report describes, the CCB has been successful in achieving these goals, and multidisciplinary computational biology is now an integral part of UC Merced undergraduate, graduate and research programs in the life sciences. The CCB began in fall 2004 with the aid of an award from U.S. Department of Energy (DOE), under its Genomes to Life program of support for the development of research and educational infrastructure in the modern biological sciences. This report to DOE describes the research and academic programs made possible by the CCB from its inception until August, 2010, at the end of the final extension. Although DOE support for the center ended in August 2010, the CCB will continue to exist and support its original objectives. The research and academic programs fostered by the CCB have led to additional extramural funding from other agencies, and we anticipate that CCB will continue to provide support for quantitative and computational biology program at UC Merced for many years to come. Since its inception in fall 2004, CCB research projects have continuously had a multi-institutional collaboration with Lawrence Livermore National Laboratory (LLNL), and the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, as well as individual collaborators at other sites. CCB affiliated faculty cover a broad range of computational and mathematical research including molecular modeling, cell biology, applied math, evolutional biology, bioinformatics, etc. The CCB sponsored the first distinguished speaker series at UC Merced, which had an important role is spreading the word about the computational biology emphasis at this new campus. One of CCB's original goals is to help train a new generation of biologists who bridge the gap between the computational and life sciences. To archive this goal, by summer 2006, a new program - summer undergraduate internship program, have been established under CCB to train the highly mathematical and computationally intensive Biological Science researchers. By the end of summer 2010, 44 undergraduate students had gone through this program. Out of those participants, 11 students have been admitted to graduate schools and 10 more students are interested in pursuing graduate studies in the sciences. The center is also continuing to facilitate the development and dissemination of undergraduate and graduate course materials based on the latest research in computational biology.« less

Cross Domain Deterrence: Livermore Technical Report, 2014-2016

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnes, Peter D.; Bahney, Ben; Matarazzo, Celeste

2016-08-03

Lawrence Livermore National Laboratory (LLNL) is an original collaborator on the project titled “Deterring Complex Threats: The Effects of Asymmetry, Interdependence, and Multi-polarity on International Strategy,” (CDD Project) led by the UC Institute on Global Conflict and Cooperation at UCSD under PIs Jon Lindsay and Erik Gartzke , and funded through the DoD Minerva Research Initiative. In addition to participating in workshops and facilitating interaction among UC social scientists, LLNL is leading the computational modeling effort and assisting with empirical case studies to probe the viability of analytic, modeling and data analysis concepts. This report summarizes LLNL work on themore » CDD Project to date, primarily in Project Years 1-2, corresponding to Federal fiscal year 2015. LLNL brings two unique domains of expertise to bear on this Project: (1) access to scientific expertise on the technical dimensions of emerging threat technology, and (2) high performance computing (HPC) expertise, required for analyzing the complexity of bargaining interactions in the envisioned threat models. In addition, we have a small group of researchers trained as social scientists who are intimately familiar with the International Relations research. We find that pairing simulation scientists, who are typically trained in computer science, with domain experts, social scientists in this case, is the most effective route to developing powerful new simulation tools capable of representing domain concepts accurately and answering challenging questions in the field.« less

Disposition and metabolism of 2,3-( UC)dichloropropene in rats after inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, J.A.; Medinsky, M.A.; Dutcher, J.S.

1985-01-01

2,3-Dichloropropene (2,3-DCP) is a constituent of some commercially available preplant soil fumigants for the control of plant parasitic nematodes. The purpose of this investigation was to determine the disposition and metabolism of 2,3-( UC)DCP in rats after inhalation. Male Fischer-344 rats were exposed nose-only to a vapor concentration of 250 nmol 2,3-( UC)DCP/liter air (7.5 ppm; 25C, 620 Torr) for 6 hr. Blood samples were taken during exposure, and urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Urinary excretion was the major route of elimination of UC (55% of estimated absorbed 2,3-DCP). Half-timemore » for elimination of UC in urine was 9.8 +/- 0.05 hr (anti x +/- SE). Half-time for elimination of UC feces (17% of absorbed 2,3-DCP) was 12.9 +/- 0.14 hr (anti x +/- SE). Approximately 1 and 3% of the estimated absorbed 2,3-( UC)DCP were exhaled as either 2,3-( UC)DCP or UCO2, respectively. Concentrations of UC in blood increased during 240 min of exposure, after which no further increases in blood concentration of UC were seen. UC was widely distributed in tissues analyzed after a 6-hr exposure of rats to 2,3-( UC)DCP. Urinary bladder (150 nmol/g), nasal turbinates (125 nmol/g), kidneys (84 nmol/g), small intestine (61 nmol/g), and liver (35 nmol/g) were tissues with the highest concentrations of UC immediately after exposure. Over 90% of the UC in tissues analyzed was 2,3-DCP metabolites. Half-times for elimination of UC from tissues examined ranged from 3 to 11 hr. The data from this study indicate that after inhalation 2,3-DCP is metabolized in tissues and readily excreted. 21 references. 2 figures, 4 tables.« less

Cool Cities, Cool Planet (LBNL Science at the Theater)

ScienceCinema

Rosenfeld, Arthur; Pomerantz, Melvin; Levinson, Ronnen

2018-06-14

Science at the Theater: Berkeley Lab scientists discuss how cool roofs can cool your building, your city ... and our planet. Arthur Rosenfeld, Professor of Physics Emeritus at UC Berkeley, founded the Berkeley Lab Center for Building Science in 1974. He served on the California Energy Commission from 2000 to 2010 and is commonly referred to as California's godfather of energy efficiency. Melvin Pomerantz is a member of the Heat Island Group at Berkeley Lab. Trained as a physicist at UC Berkeley, he specializes in research on making cooler pavements and evaluating their effects. Ronnen Levinson is a staff scientist at Berkeley Lab and the acting leader of its Heat Island Group. He has developed cool roofing and paving materials and helped bring cool roof requirements into building energy efficiency standards.

Evidence to Support Monitoring of Vedolizumab Trough Concentrations in Patients With Inflammatory Bowel Diseases.

PubMed

Dreesen, Erwin; Verstockt, Bram; Bian, Sumin; de Bruyn, Magali; Compernolle, Griet; Tops, Sophie; Noman, Maja; Van Assche, Gert; Ferrante, Marc; Gils, Ann; Vermeire, Séverine

2018-04-25

Trough concentrations of vedolizumab were found to correlate with clinical response in phase 3 studies of patients with ulcerative colitis (UC) or Crohn's disease (CD). Nevertheless, there are no solid data to support monitoring of vedolizumab trough concentrations in treated patients. We investigated the correlation between vedolizumab exposure and response in a real-world population and aimed to identify patient factors that affect exposure and response. We performed a retrospective cohort study of 179 consecutive patients (66 with UC and 113 with CD) who began vedolizumab therapy from September 1, 2015, through October 1, 2016, at University Hospitals Leuven, Belgium. Serum concentrations of vedolizumab were measured before all infusions up to week 30. Effectiveness endpoints included endoscopic healing (UC, Mayo endoscopic sub-score ≤1; CD, absence of ulcers), clinical response (physicians' global assessment), and biologic response or remission (based on level of C-reactive protein) and were assessed at week 14 (for patients with UC) and week 22 (for patients with CD). A stepwise forward addition-backward elimination modeling approach was performed to identify factors independently associated with vedolizumab exposure and response. Vedolizumab trough concentrations >30.0 μg/mL at week 2, >24.0 μg/mL at week 6, and >14.0 μg/mL during maintenance therapy associated with a higher probability of attaining the effectiveness endpoints for patients with UC or CD (P < .05). Higher body mass and more severe disease (based on high level of C-reactive protein and low level of albumin and/or hemoglobin) at the start of vedolizumab therapy associated with lower trough concentrations of vedolizumab over the 30-week period and a lower probability of achieving mucosal healing (P < .05). Mucosal healing was achieved in significantly more patients with UC than patients with CD, even though a diagnosis of UC was not an independent predictor of higher vedolizumab trough concentrations. In a retrospective study of 179 patients with CD or UC, we observed a correlation between vedolizumab exposure and response. These findings support monitoring of vedolizumab trough concentrations to predict patients' outcome. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Sleep duration affects risk for ulcerative colitis: a prospective cohort study.

PubMed

Ananthakrishnan, Ashwin N; Khalili, Hamed; Konijeti, Gauree G; Higuchi, Leslie M; de Silva, Punyanganie; Fuchs, Charles S; Richter, James M; Schernhammer, Eva S; Chan, Andrew T

2014-11-01

Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with >90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration <6 h/day (11/100,000 person-years) or >9 h/day (20/100,000 person-years) had a higher incidence of UC (P < .05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations <6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations >9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Receptivity of a Cryogenic Coaxial Gas-Liquid Jet to Acoustic Disturbances (Briefing Charts)

DTIC Science & Technology

2014-03-01

meas = Δt Δs Uc,meas 2/12/1 0 2/12/1 0 , i iio thc UUU      DISTRIBUTION STATEMENT A. Approved for public release; distribution unlimited...this point, dynamic pressures are approximately equal. Uc Uo – Uc Uc – Ui (Uo > Ui) 2/12/1 2/12/1 io iioo c UUU      St = Uc fnatD If St, D, Uc

Receptivity of a Cryogenic Coaxial Liquid Jet to Acoustic Disturbances

DTIC Science & Technology

2014-05-21

i iio thc UUU DISTRIBUTION STATEMENT A. Approved for public release; distribution unlimited. PA Clearance 14208 12Place Proper DISTRIBUTION STATEMENT...dynamic pressures are approximately equal. Uc Uo – Uc Uc – Ui (Uo > Ui) 2/12/1 2/12/1 io iioo c UUU St = Uc fnatD If St, D, Uc are held constant then

Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis.

PubMed

Knoll, Rebecca L; Forslund, Kristoffer; Kultima, Jens Roat; Meyer, Claudius U; Kullmer, Ulrike; Sunagawa, Shinichi; Bork, Peer; Gehring, Stephan

2017-04-01

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD. Copyright © 2017 the American Physiological Society.

Visualising elastic anisotropy: theoretical background and computational implementation

NASA Astrophysics Data System (ADS)

Nordmann, J.; Aßmus, M.; Altenbach, H.

2018-02-01

In this article, we present the technical realisation for visualisations of characteristic parameters of the fourth-order elasticity tensor, which is classified by three-dimensional symmetry groups. Hereby, expressions for spatial representations of uc(Young)'s modulus and bulk modulus as well as plane representations of shear modulus and uc(Poisson)'s ratio are derived and transferred into a comprehensible form to computer algebra systems. Additionally, we present approaches for spatial representations of both latter parameters. These three- and two-dimensional representations are implemented into the software MATrix LABoratory. Exemplary representations of characteristic materials complete the present treatise.

Ulcerative colitis-associated colorectal cancer

PubMed Central

Yashiro, Masakazu

2014-01-01

The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC. PMID:25469007

Intraepithelial lymphocyte eotaxin-2 expression and perineural mast cell degranulation differentiate allergic/eosinophilic colitis from classic IBD.

PubMed

Torrente, Franco; Barabino, Arrigo; Bellini, Tommaso; Murch, Simon H

2014-09-01

Allergic colitis shows overlap with classic inflammatory bowel disease (IBD). Clinically, allergic colitis is associated with dysmotility and abdominal pain, and mucosal eosinophilia is characteristic. We thus aimed to characterise mucosal changes in children with allergic colitis compared with normal tissue and classic IBD, focusing on potential interaction between eosinophils and mast cells with enteric neurones. A total of 15 children with allergic colitis, 10 with Crohn disease (CD), 10 with ulcerative colitis (UC), and 10 histologically normal controls were studied. Mucosal biopsies were stained for CD3 T cells, Ki-67, eotaxin-1, and eotaxin-2. Eotaxin-2, IgE, and tryptase were localised compared with mucosal nerves, using neuronal markers neurofilament protein, neuron-specific enolase, and nerve growth factor receptor. Overall inflammation was greater in patients with CD and UC than in patients with allergic colitis. CD3 T-cell density was increased in patients with allergic colitis, similar to that in patients with CD but lower than in patients with UC, whereas eosinophil density was higher than in all other groups. Eotaxin-1 and -2 were localised to basolateral crypt epithelium in all specimens, with eotaxin-1+ lamina propria cells found in all of the colitis groups. Eotaxin-2+ intraepithelial lymphocyte (IEL) density was significantly higher in allergic colitis specimens than in all other groups. Mast cell degranulation was strikingly increased in patients with allergic colitis (12/15) compared with that in patients with UC (1/10) and CD (0/1). Tryptase and IgE colocalised on enteric neurons in patients with allergic colitis but rarely in patients with IBD. Eotaxin-2+ IELs may contribute to the periepithelial eosinophil accumulation characteristic of allergic colitis. The colocalisation of IgE and tryptase with mucosal enteric nerves is likely to promote the dysmotility and visceral hyperalgesia classically seen in allergic gastrointestinal inflammation.

e-Care for heart wellness: a feasibility trial to decrease blood pressure and cardiovascular risk.

PubMed

Green, Beverly B; Anderson, Melissa L; Cook, Andrea J; Catz, Sheryl; Fishman, Paul A; McClure, Jennifer B; Reid, Robert J

2014-04-01

Pharmacist- or nurse-led team care decreases patient blood pressure (BP) and cardiovascular disease (CVD) risk. To evaluate whether a Web-based dietitian-led (WD) team care intervention was feasible and resulted in decreased BP, CVD risk, and weight compared to usual care (UC). Electronic health record (EHR) data identified patients aged 30-69 years with BMI >26, elevated BP, and 10%-25% 10-year Framingham CVD risk who were registered patient website users. Patients with uncontrolled BP at screening were randomized to UC or WD, which included a home BP monitor, scale, and dietitian team care. WD participants had a single in-person dietitian visit to obtain baseline information and create a plan to reduce CVD risk. Planned follow-up occurred via secure messaging to report BP, weight, and fruit and vegetable intake and receive ongoing feedback. If needed, dietitians encouraged patients and their physicians to intensify antihypertensive and lipid-lowering medications. Primary outcomes were change in systolic BP and weight loss ≥4 kg at 6 months. Feasibility outcomes included intervention utilization and satisfaction. Between 2010 and 2011, a total of 90 of 101 participants completed 6-month follow-ups. The WD group had higher rates of secure messaging utilization and patient satisfaction. The WD group lost significantly more weight than the UC group (adjusted net difference=-3.2 kg, 95% CI=-5.0, -1.5, p<0.001) and was more likely to lose ≥4 kg (adjusted relative risk [RRadj]=2.96, 95% CI=1.16, 7.53). BP control and CVD risk reduction were greater in WD than UC, but differences were not statistically significant. WD intervention was feasible and resulted in decreased weight, BP, and CVD risk. A larger trial is justified. Trial Registration Number: NCT01077388. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Kishi, Taro; Hirota, Tomoya; Matsunaga, Shinji; Iwata, Nakao

2016-07-01

We performed an updated meta-analysis of antipsychotic treatment in patients with delirium, based on a previous meta-analysis published in 2007. Included in this study were randomised, placebo-controlled or usual care (UC) controlled trials of antipsychotics in adult patients with delirium. Our primary outcome measure was response rate at the study end point. The secondary outcome measures included improvement of severity of delirium, Clinical Global Impression-Severity Scale (CGI-S), time to response (TTR), discontinuation rate and individual adverse effects. The risk ratio (RR), the number-needed-to-treat/harm (NNT/NNH), 95% CIs and standardised mean difference (SMD), were calculated. We identified 15 studies (mean duration: 9.8 days) for the systematic review (total n=949, amisulpride=20, aripiprazole=8, chlorpromazine=13, haloperidol=316, intramuscular olanzapine or haloperidol injection=62, olanzapine=144, placebo=75, quetiapine=125, risperidone=124, UC=30 and ziprasidone=32), 4 of which were conference abstracts and unpublished. When pooled as a group, antipsychotics were superior to placebo/UC in terms of response rate (RR=0.22, NNT=2), delirium severity scales scores (SMD=-1.27), CGI-S scores (SMD=-1.57) and TTR (SMD=-1.22). The pooled antipsychotic group was associated with a higher incidence of dry mouth (RR=13.0, NNH=5) and sedation (RR=4.59, NNH=5) compared with placebo/UC. Pooled second-generation antipsychotics (SGAs) were associated with shorter TTR (SMD=-0.27) and a lower incidence of extrapyramidal symptoms (RR=0.31, NNH=7) compared with haloperidol. Our results suggested that SGAs have a benefit for the treatment of delirium with regard to efficacy and safety compared with haloperidol. However, further study using larger samples is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients.

PubMed

Jonkers, Daisy; Penders, John; Masclee, Ad; Pierik, Marieke

2012-04-16

Mounting evidence suggests an important role for the intestinal microbiota in the chronic mucosal inflammation that occurs in inflammatory bowel disease (IBD), and novel molecular approaches have further identified a dysbiosis in these patients. Several mechanisms of action of probiotic products that may interfere with possible aetiological factors in IBD have been postulated. Our objective was to discuss the rationale for probiotics in IBD and to systematically review clinical intervention studies with probiotics in the management of IBD in adults. A systematic search was performed in PubMed up to 1 October 2011, using defined keywords. Only full-text papers in the English language addressing clinical outcomes in adult patients were included. The 41 eligible studies were categorized on disease type (ulcerative colitis [UC] with/without an ileo-anal pouch and Crohn's disease [CD]) and disease activity. Pooled odds ratios were only calculated per probiotic for a specific patient group when more than one randomized controlled trial was available. Well designed randomized controlled trials supporting the application of probiotics in the management of IBD are still limited. Meta-analyses could only be performed for a limited number of studies revealing overall risk ratios of 2.70 (95% CI 0.47, 15.33) for inducing remission in active UC with Bifido-fermented milk versus placebo or no additive treatment (n = 2); 1.88 (95% CI 0.96, 3.67) for inducing remission in active UC with VSL#3 versus placebo (n = 2); 1.08 (95% CI 0.86, 1.37) for preventing relapses in inactive UC with Escherichia coli Nissle 1917 versus standard treatment (n = 3); 0.17 (95% CI 0.09, 0.33) for preventing relapses in inactive UC/ileo-anal pouch anastomosis (IPAA) patients with VSL#3 versus placebo; 1.21 (95% CI 0.57, 2.57) for preventing endoscopic recurrences in inactive CD with Lactobacillus rhamnosus GG versus placebo (n = 2); and 0.93 (95% CI 0.63, 1.38) for preventing endoscopic recurrences in inactive CD with Lactobacillus johnsonii versus placebo (n = 2). Further well designed studies based on intention-to-treat analyses by several independent research groups are still warranted to support the promising results for E. coli Nissle in inactive UC and the multispecies product VSL#3 in active UC and inactive pouch patients. So far, no evidence is available to support the use of probiotics in CD. Future studies should focus on specific disease subtypes and disease location. Further insight into the aetiology of IBD and the mechanisms of probiotic strains will aid in selecting probiotic strains for specific disease entities and disease locations.

A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy

PubMed Central

2011-01-01

Background Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective. Methods A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research. Results PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty. Conclusions Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY). PMID:22051143

Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

PubMed

Paramsothy, Sudarshan; Paramsothy, Ramesh; Rubin, David T; Kamm, Michael A; Kaakoush, Nadeem O; Mitchell, Hazel M; Castaño-Rodríguez, Natalia

2017-10-01

Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD. A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model. In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188; I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased diversity and a shift in recipient microbiota profile towards the donor post-FMT. FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features.

PubMed

Mai, Kien T; Truong, Luan D; Ball, Christopher G; Williams, Phillip; Flood, Trevor A; Belanger, Eric C

2015-08-01

We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women.

PubMed

Centi, Amanda J; Booth, Sarah L; Gundberg, Caren M; Saltzman, Edward; Nicklas, Barbara; Shea, M Kyla

2015-12-01

Osteocalcin (OC) is a vitamin K-dependent bone protein used as a marker of bone formation. Mouse models have demonstrated a role for the uncarboxylated form of OC (ucOC) in energy metabolism, including energy expenditure and adiposity, but human data are equivocal. The purpose of this study was to determine the associations between changes in measures of OC and changes in body weight and percent body fat in obese, but otherwise healthy post-menopausal women undergoing a 20-week weight loss program. All participants received supplemental vitamins K and D and calcium. Body weight and body fat percentage (%BF) were assessed before and after the intervention. Serum OC [(total (tOC), ucOC, percent uncarboxylated (%ucOC)], and procollagen type 1N-terminal propeptide (P1NP; a measure of bone formation) were measured. Women lost an average of 10.9 ± 3.9 kg and 4 %BF. Serum concentrations of tOC, ucOC, %ucOC, and P1NP did not significantly change over the twenty-week intervention, nor were these measures associated with changes in weight (all p > 0.27) or %BF (all p > 0.54). Our data do not support an association between any serum measure of OC and weight or %BF loss in post-menopausal women supplemented with nutrients implicated in bone health.

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis.

PubMed

Ashraf, Imran; Choudhary, Abhishek; Arif, Murtaza; Matteson, Michelle L; Hammad, Hazem T; Puli, Srinivas R; Bechtold, Matthew L

2012-04-01

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC. Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I (2) measure of inconsistency. RevMan 5 was utilized for statistical analysis. Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19-1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18-1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC. Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

Effects of a pre-visit educational website on information recall and needs fulfilment in breast cancer genetic counselling, a randomized controlled trial.

PubMed

Albada, Akke; van Dulmen, Sandra; Bensing, Jozien M; Ausems, Margreet G E M

2012-03-06

Pre-visit education which helps counselees to prepare for their first visit for breast cancer genetic counseling might enhance information recall and needs fulfilment. This study assessed the effects of a pre-visit website with tailored information and question prompt sheet (QPS), named E-info geneca. A total of 197 counselees were randomized to receive usual care (UC) or UC plus E-info geneca. All counselees completed a pre- and post-visit questionnaire and visits were videotaped. We studied effects on counselees' information recall, knowledge about breast cancer and heredity, fulfillment of needs, risk perception alignment, anxiety and perceived personal control, using multilevel regression analyses. Intent-to-treat analysis showed that counselees in the intervention group (n = 103) had higher levels of recall of information from the consultation (β = .32; confidence interval (CI): .04 to .60; P = .02; d = .17) and post-visit knowledge of breast cancer and heredity (β = .30; CI: .03 to .57; P = .03) than counselees in the UC group (n = 94). Also, intervention group counselees reported better fulfilment of information needs (β = .31; CI: .03 to .60; P = .03). The effects of the intervention were strongest for those counselees who did not receive an indication for DNA testing. Their recall scores showed a larger increase (β = .95; CI: .32 to 1.59; P = .003; d = .30) and their anxiety levels dropped more in the intervention compared to the UC group (β = -.60; CI: -1.12 to -.09; P = .02). No intervention effects were found after the first visit on risk perception alignment or perceived personal control. This study shows that pre-counseling education, using tailored information technology, leads to more effective first visits for breast cancer genetic counseling, in particular for counselees who received no indication for DNA testing and, therefore, had no indication for a second visit. Future study should focus on the effects of a pre-visit website on the outcomes after a complete series of visits. Dutch Trial Register ISRCTN82643064.

Effects of a pre-visit educational website on information recall and needs fulfilment in breast cancer genetic counselling, a randomized controlled trial

PubMed Central

2012-01-01

Introduction Pre-visit education which helps counselees to prepare for their first visit for breast cancer genetic counseling might enhance information recall and needs fulfilment. This study assessed the effects of a pre-visit website with tailored information and question prompt sheet (QPS), named E-info geneca. Methods A total of 197 counselees were randomized to receive usual care (UC) or UC plus E-info geneca. All counselees completed a pre- and post-visit questionnaire and visits were videotaped. We studied effects on counselees' information recall, knowledge about breast cancer and heredity, fulfillment of needs, risk perception alignment, anxiety and perceived personal control, using multilevel regression analyses. Results Intent-to-treat analysis showed that counselees in the intervention group (n = 103) had higher levels of recall of information from the consultation (β = .32; confidence interval (CI): .04 to .60; P = .02; d = .17) and post-visit knowledge of breast cancer and heredity (β = .30; CI: .03 to .57; P = .03) than counselees in the UC group (n = 94). Also, intervention group counselees reported better fulfilment of information needs (β = .31; CI: .03 to .60; P = .03). The effects of the intervention were strongest for those counselees who did not receive an indication for DNA testing. Their recall scores showed a larger increase (β = .95; CI: .32 to 1.59; P = .003; d = .30) and their anxiety levels dropped more in the intervention compared to the UC group (β = -.60; CI: -1.12 to -.09; P = .02). No intervention effects were found after the first visit on risk perception alignment or perceived personal control. Conclusions This study shows that pre-counseling education, using tailored information technology, leads to more effective first visits for breast cancer genetic counseling, in particular for counselees who received no indication for DNA testing and, therefore, had no indication for a second visit. Future study should focus on the effects of a pre-visit website on the outcomes after a complete series of visits. Trial registration Dutch Trial Register ISRCTN82643064. PMID:22394647

Preventing Loss of Independence through Exercise (PLIÉ): A Pilot Clinical Trial in Older Adults with Dementia

PubMed Central

Barnes, Deborah E.; Mehling, Wolf; Wu, Eveline; Beristianos, Matthew; Yaffe, Kristine; Skultety, Karyn; Chesney, Margaret A.

2015-01-01

Background Current dementia medications have small effect sizes, many adverse effects and do not change the disease course. Therefore, it is critically important to study alternative treatment strategies. The goal of this study was to pilot-test a novel, integrative group exercise program for individuals with mild-to-moderate dementia called Preventing Loss of Independence through Exercise (PLIÉ), which focuses on training procedural memory for basic functional movements (e.g., sit-to-stand) while increasing mindful body awareness and facilitating social connection. Methods We performed a 36-week cross-over pilot clinical trial to compare PLIÉ with usual care (UC) at an adult day program for individuals with dementia in San Francisco, CA. Assessments of physical performance, cognitive function, physical function, dementia-related behaviors, quality of life and caregiver burden were performed by blinded assessors at baseline, 18 weeks (cross-over) and 36 weeks. Our primary outcomes were effect sizes based on between-group comparisons of change from baseline to 18 weeks; secondary outcomes were within-group comparisons of change before and after cross-over. Results Twelve individuals enrolled (7 PLIÉ, 5 UC) and 2 withdrew (1 PLIÉ, 18 weeks; 1 UC, 36 weeks). Participants were 82% women (mean age, 84 ± 4 years); caregivers were 82% daughters (mean age, 56 ± 13 years). Effect sizes were not statistically significant but suggested potentially clinically meaningful (≥0.25 SDs) improvement with PLIÉ versus UC for physical performance (Cohen’s D: 0.34 SDs), cognitive function (0.76 SDs) and quality of life (0.83 SDs) as well as for caregiver measures of participant’s quality of life (0.33 SDs) and caregiver burden (0.49 SDs). Results were similar when within-group comparisons were made before and after cross-over. Conclusions PLIÉ is a novel, integrative exercise program that shows promise for improving physical function, cognitive function, quality of life and caregiver burden in individuals with mild-to-moderate dementia. Larger randomized, controlled trials are warranted. Trial Registration ClinicalTrials.gov NCT01371214 PMID:25671576

The effect of intravesical chemotherapy in the prevention of intravesical recurrence after nephroureterectomy for upper tract urothelial carcinoma: a meta-analysis.

PubMed

Yuan, Haichao; Mao, Xiangming; Bai, Yunjin; Li, Hengping; Liu, Liangren; Pu, Chunxiao; Li, Jinhong; Tang, Yin; Wei, Qiang; Han, Ping

2015-08-01

The standard management of upper urinary tract urothelial carcinoma (UUT-UC) is nephroureterectomy with bladder cuff excision, but after surgery, approximately 22-47% of patients with UUT-UC develop subsequent bladder tumour recurrence, potentially because of the implantation of cancer cells from the primary tumour. To conduct a meta-analysis to evaluate the effect of prophylactic intravesical chemotherapy in the prevention of bladder recurrence after nephroureterectomy for UUT-UC. An electronic database search of Medline, Embase, the Cochrane Library, CancerLit and ClinicalTrials.gov was performed to identify appropriate studies prior to March 2013.All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The main outcome measure for this meta-analysis was the rate of bladder recurrence after nephroureterectomy. The search was not limited by language. The review process followed the guidelines of the Cochrane Collaboration. The analysis was conducted using the Review Manager Version RevMan 5.0 software (The Nordic Cochrane Centre, The Cochrane Collaboration). A total of 592 patients were included in this study, of whom 257 underwent intravesical instillation after nephroureterectomy and 335 underwent nephroureterectomy alone. Our meta-analysis demonstrated that the rate of recurrence after 12 months was significantly lower in the intravesical instillation after nephroureterectomy group than in the nephroureterectomy-alone group [odds ratio (OR): 0.48; 95% confidence interval (CI): 0.28-0.81; P = 0.006]. A significant decrease in bladder recurrence after at least 24  months was also observed in the intravesical instillation after nephroureterectomy group (OR: 0.40; 95% CI: 0.24-0.67; P = 0.0004). A subgroup analysis demonstrated that the pattern of differences was similar to those from the total group analysis. Prophylactic intravesical chemotherapy was effective for the prevention of bladder recurrence after nephroureterectomy. Therefore, we suggest that prophylactic intravesical chemotherapy should be performed in patients with UUT-UC after nephroureterectomy, but the optimal chemotherapy regimen and the initial time of instillation should be explored in future studies.

Peripheral Nerve Stimulation Compared to Usual Care for Pain Relief of Hemiplegic Shoulder Pain: A Randomized Controlled Trial

PubMed Central

Wilson, Richard D.; Gunzler, Douglas D.; Bennett, Maria E.; Chae, John

2014-01-01

Objective This study seeks to establish the efficacy of single-lead, 3-week peripheral nerve stimulation (PNS) therapy for pain reduction in stroke survivors with chronic hemiplegic shoulder pain. Design Single-site, pilot, randomized controlled trial for adults with chronic shoulder pain after stroke. Participants were randomized to receive a 3-week treatment of single-lead PNS or usual care (UC). The primary outcome was the worst pain in the last week (Brief Pain Inventory, Short Form question 3) measured at baseline, and weeks 1,4, 12, and 16. Secondary outcomes included pain interference (Brief Pain Inventory, Short Form question 9), pain measured by the ShoulderQ Visual Graphic Rating Scales; and health-related quality of life (SF-36v2). Results Twenty-five participants were recruited, 13 to PNS and 12 to UC. There was a significantly greater reduction in pain for the PNS group compared to controls, with significant differences at 6 and 12 weeks after treatment. Both PNS and UC were associated with significant improvements in pain interference and physical health related quality of life. Conclusions Short-term PNS is a safe and efficacious treatment for shoulder pain. Pain reduction is greater than compared to UC and is maintained for at least 12 weeks after treatment. PMID:24355994

Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators.

PubMed

Kannan, Narayanan; Guruvayoorappan, Chandrasekharan

2013-05-01

Inflammatory bowel diseases (IBD), including Crohn's disease and Ulcerative colitis (UC), are life-long and recurrent disorders of the gastrointestinal tract with unknown etiology. The present study is designed to evaluate the ameliorative effect of Bauhinia tomentosa during ulcerative colitis (UC). Three groups of animals (n=6) were treated with B. tomentosa (5, 10, 20 mg/kg B.wt respectively) for 5 consecutive days before induction of UC. UC was induced by intracolonic injection of 3% acetic acid. The colonic mucosal injury was assessed by macroscopic scoring and histological examination. Furthermore, the mucosal content of lipid peroxidation (LPO), reduced glutathione (GSH), nitric oxide (NO), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity confirms that B. tomentosa could significantly inhibit colitis in a dose dependent manner. The myeloperoxidase (MPO), tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS) expression studies and lactate dehydrogenase (LDH) assay also supported that B. tomentosa could significantly inhibit experimental colitis. The effect was comparable to the standard drug sulfasalazine. Colonic mucosal injury parallels with the result of histological and biochemical evaluations. The extracts obtained from B. tomentosa possess active substances, which exert marked protective effects in acute experimental colitis, possibly by regulating the antioxidant and inflammatory mediators. Copyright © 2013 Elsevier B.V. All rights reserved.

Explanation of inequality in utilization of ambulatory care before and after universal health insurance in Thailand

PubMed Central

Yiengprugsawan, V; Carmichael, GA; Lim, LL-Y; Seubsman, S; Sleigh, AC

2011-01-01

Thailand implemented a Universal Coverage Scheme (UCS) of national health insurance in April 2001 to finance equitable access to health care. This paper compares inequalities in health service use before and after the UCS, and analyses the trend and determinants of inequality. The national Health and Welfare Surveys of 2001 and 2005 are used for this study. The concentration index for use of ambulatory care among the population reporting a recent illness is used as a measure of health inequality, decomposed into contributing demographic, socio-economic, geographic and health insurance determinants. As a result of the UCS, the uninsured group fell from 24% in 2001 to 3% in 2005 and health service patterns changed. Use of public primary health care facilities such as health centres became more concentrated among the poor, while use of provincial/general hospitals became more concentrated among the better-off. Decomposition analysis shows that the increasingly common use of health centres among the poor in 2005 was substantially associated with those with lower income, residence in the rural northeast and the introduction of the UCS. The increasing use of provincial/general hospitals and private clinics among the better-off in 2005 was substantially associated with the government and private employee insurance schemes. Although the UCS scheme has achieved its objective in increasing insurance coverage and utilization of primary health services, our findings point to the need for future policies to focus on the quality of this primary care and equitable referrals to secondary and tertiary health facilities when required. PMID:20736414

Nurse management for hypertension. A systems approach.

PubMed

Rudd, Peter; Miller, Nancy Houston; Kaufman, Judy; Kraemer, Helena C; Bandura, Albert; Greenwald, George; Debusk, Robert F

2004-10-01

Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP. We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period. Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group. Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.

Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial.

PubMed

Gordon, Glenn L; Zakko, Salam; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ronald; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P; Lichtenstein, Gary R

2016-04-01

To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. Mesalamine is a first-line treatment for induction and maintenance of UC remission. A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia.

PubMed

Bista, Rajan K; Brentnall, Teresa A; Bronner, Mary P; Langmead, Christopher J; Brand, Randall E; Liu, Yang

2011-12-01

Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting, and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study was to evaluate whether optical markers of rectal mucosa derived from a novel optical technique, partial-wave spectroscopic microscopy (PWS), could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. Banked frozen nondysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross-validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Cloning and Characterization of the Pyrrolomycin Biosynthetic Gene Clusters from Actinosporangium vitaminophilum ATCC 31673 and Streptomyces sp. Strain UC 11065▿

PubMed Central

Zhang, Xiujun; Parry, Ronald J.

2007-01-01

The pyrrolomycins are a family of polyketide antibiotics, some of which contain a nitro group. To gain insight into the nitration mechanism associated with the formation of these antibiotics, the pyrrolomycin biosynthetic gene cluster from Actinosporangium vitaminophilum was cloned. Sequencing of ca. 56 kb of A. vitaminophilum DNA revealed 35 open reading frames (ORFs). Sequence analysis revealed a clear relationship between some of these ORFs and the biosynthetic gene cluster for pyoluteorin, a structurally related antibiotic. Since a gene transfer system could not be devised for A. vitaminophilum, additional proof for the identity of the cloned gene cluster was sought by cloning the pyrrolomycin gene cluster from Streptomyces sp. strain UC 11065, a transformable pyrrolomycin producer. Sequencing of ca. 26 kb of UC 11065 DNA revealed the presence of 17 ORFs, 15 of which exhibit strong similarity to ORFs in the A. vitaminophilum cluster as well as a nearly identical organization. Single-crossover disruption of two genes in the UC 11065 cluster abolished pyrrolomycin production in both cases. These results confirm that the genetic locus cloned from UC 11065 is essential for pyrrolomycin production, and they also confirm that the highly similar locus in A. vitaminophilum encodes pyrrolomycin biosynthetic genes. Sequence analysis revealed that both clusters contain genes encoding the two components of an assimilatory nitrate reductase. This finding suggests that nitrite is required for the formation of the nitrated pyrrolomycins. However, sequence analysis did not provide additional insights into the nitration process, suggesting the operation of a novel nitration mechanism. PMID:17158935

Web-Based Mindfulness Intervention in Heart Disease: A Randomized Controlled Trial

PubMed Central

Younge, John O.; Wery, Machteld F.; Gotink, Rinske A.; Utens, Elisabeth M. W. J.; Michels, Michelle; Rizopoulos, Dimitris; van Rossum, Elisabeth F. C.

2015-01-01

Background Evidence is accumulating that mindfulness training has favorable effects on psychological outcomes, but studies on physiological outcomes are limited. Patients with heart disease have a high incidence of physiological and psychological problems and may benefit from mindfulness training. Our aim was to determine the beneficial physiological and psychological effects of online mindfulness training in patients with heart disease. Methods The study was a pragmatic randomized controlled single-blind trial. Between June 2012 and April 2014 we randomized 324 patients (mean age 43.2 years, 53.7% male) with heart disease in a 2:1 ratio (n = 215 versus n = 109) to a 12-week online mindfulness training in addition to usual care (UC) compared to UC alone. The primary outcome was exercise capacity measured with the 6 minute walk test (6MWT). Secondary outcomes were other physiological parameters (heart rate, blood pressure, respiratory rate, and NT-proBNP), subjective health status (SF-36), perceived stress (PSS), psychological well-being (HADS), social support (PSSS12) and a composite endpoint (all-cause mortality, heart failure, symptomatic arrhythmia, cardiac surgery, and percutaneous cardiac intervention). Linear mixed models were used to evaluate differences between groups on the repeated outcome measures. Results Compared to UC, mindfulness showed a borderline significant improved 6MWT (effect size, meters: 13.2, 95%CI: -0.02; 26.4, p = 0.050). There was also a significant lower heart rate in favor of the mindfulness group (effect size, beats per minute: -2.8, 95%CI: -5.4;-0.2, p = 0.033). No significant differences were seen on other outcomes. Conclusions Mindfulness training showed positive effects on the physiological parameters exercise capacity and heart rate and it might therefore be a useful adjunct to current clinical therapy in patients with heart disease. Trial Registration Dutch Trial Register 3453 PMID:26641099

Effectiveness of school-based humanistic counselling for psychological distress in young people: Pilot randomized controlled trial with follow-up in an ethnically diverse sample.

PubMed

Pearce, Peter; Sewell, Ros; Cooper, Mick; Osman, Sarah; Fugard, Andrew J B; Pybis, Joanne

2017-06-01

The aim of this study was to pilot a test of the effectiveness of school-based humanistic counselling (SBHC) in an ethnically diverse group of young people (aged 11-18 years old), with follow-up assessments at 6 and 9 months. Pilot randomized controlled trial, using linear-mixed effect modelling and intention-to-treat analysis to compare changes in levels of psychological distress for participants in SBHC against usual care (UC). ISRCTN44253140. In total, 64 young people were randomized to either SBHC or UC. Participants were aged between 11 and 18 (M = 14.2, SD = 1.8), with 78.1% of a non-white ethnicity. The primary outcome was psychological distress at 6 weeks (mid-therapy), 12 weeks (end of therapy), 6-month follow-up and 9-month follow-up. Secondary measures included emotional symptoms, self-esteem and attainment of personal goals. Recruitment and retention rates for the study were acceptable. Participants in the SBHC condition, as compared with participants in the UC condition, showed greater reductions in psychological distress and emotional symptoms, and greater improvements in self-esteem, over time. However, at follow-up, only emotional symptoms showed significant differences across groups. The study adds to the pool of evidence suggesting that SBHC can be tested and that it brings about short-term reductions in psychological and emotional distress in young people, across ethnicities. However, there is no evidence of longer-term effects. School-based humanistic counselling can be an effective means of reducing the psychological distress experienced by young people with emotional symptoms in the short term. The short-term effectiveness of school-based humanistic counselling is not limited to young people of a White ethnicity. There is no evidence that school-based humanistic counselling has effects beyond the end of therapy. © 2016 The British Psychological Society.

The homing of human umbilical cord-derived mesenchymal stem cells and the subsequent modulation of macrophage polarization in type 2 diabetic mice.

PubMed

Yin, Yaqi; Hao, Haojie; Cheng, Yu; Gao, Jieqing; Liu, Jiejie; Xie, Zongyan; Zhang, Qi; Zang, Li; Han, Weidong; Mu, Yiming

2018-07-01

Umbilical cord-derived mesenchymal stem cells (UC-MSCs), with both immunomodulatory and pro-regenerative properties, are promising for the treatment of type 2 diabetes mellitus (T2DM). As efficient cell therapy largely relies on appropriate homing to target tissues, knowing where and to what extent injected UC-MSCs have homed is critically important. However, bio-distribution data for UC-MSCs in T2DM subjects are extremely limited. Beneficial effects of UC-MSCs on T2DM subjects are associated with increased M2 macrophages, but no systemic evaluation of M2 macrophages has been performed in T2DM individuals. In this study, we treated T2DM mice with CM-Dil-labelled UC-MSCs. UC-MSC infusion not only exerted anti-diabetic effects but also alleviated dyslipidemia and improved liver function in T2DM mice. To compare UC-MSC migration between T2DM and normal subjects, a collection of normal mice also received UC-MSC transplantation. UC-MSCs homed to the lung, liver and spleen in both normal and T2DM recipients. Specifically, the spleen harbored the largest number of UC-MSCs. Unlike normal mice, a certain number of UC-MSCs also homed to pancreatic islets in T2DM mice, which suggested that UC-MSC homing may be closely related to tissue damage. Moreover, the number of M2 macrophages in the islets, liver, fat and muscle significantly increased after UC-MSC infusion, which implied a strong link between the increased M2 macrophages and the improved condition in T2DM mice. Additionally, an M2 macrophage increase was also observed in the spleen, suggesting that UC-MSCs might exert systemic effects in T2DM individuals by modulating macrophages in immune organs. Copyright © 2018 Elsevier B.V. All rights reserved.

Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF

PubMed Central

Deng, Yinan; Zhang, Yingcai; Ye, Linsen; Zhang, Tong; Cheng, Jintao; Chen, Guihua; Zhang, Qi; Yang, Yang

2016-01-01

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs. PMID:27917866

Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF.

PubMed

Deng, Yinan; Zhang, Yingcai; Ye, Linsen; Zhang, Tong; Cheng, Jintao; Chen, Guihua; Zhang, Qi; Yang, Yang

2016-12-05

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs.

A brief history of the Bioengineering Institute of California and the UC System-wide Symposia.

PubMed

Chien, Shu

2011-04-01

The plan to establish a Multicampus Research Unit (MRU) on Bioengineering in the University of California (UC) System started in August 1999. The cooperative efforts of the UC campuses led to the formal establishment of the Bioengineering Institute of California (BIC) in October 2003. Three years prior to the BIC establishment, the System-wide Annual Bioengineering Symposium was started at UC Davis. The Symposia were then hosted sequentially by UC Santa Barbara, UC Berkeley, UCSD, UC Santa Cruz, UC Irvine, UCSF, UCLA, and UC Riverside, with the completion of the first cycle of a decade in the newest campus of UC Merced in 2009. The second cycle began in 2010 with the Symposium returning again to UC Davis. Each campus hosted a wonderful Symposium, with the active participation of students and faculty from all campuses, with the motto of "Ten campuses united as one, learning and growing together." These Symposia have contributed significantly to the collaborative research and training of students and young scientists in bioengineering, as well as fruitful interactions with industry and government agencies, which have provided strong support for these valuable meetings. The BIC will endeavor to further enhance these efforts by fostering research collaborations and joint education and training activities, with the ultimate goal of advancing bioengineering for the improvement of human health and wellbeing.

Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

PubMed

Robinson, Mike J F; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C

2015-08-01

Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever-conditioned stimulus; CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in 3 successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the CS+ lever versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also reported that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. (c) 2015 APA, all rights reserved).

Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues

PubMed Central

Robinson, Mike J.F.; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C.

2015-01-01

Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine-sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in three successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the lever CS+ versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also report that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions together did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. PMID:26076340

Effect of a telemonitoring-facilitated collaboration between general practitioner and heart failure clinic on mortality and rehospitalization rates in severe heart failure: the TEMA-HF 1 (TElemonitoring in the MAnagement of Heart Failure) study.

PubMed

Dendale, Paul; De Keulenaer, Gilles; Troisfontaines, Pierre; Weytjens, Caroline; Mullens, Wilfried; Elegeert, Ivan; Ector, Bavo; Houbrechts, Marita; Willekens, Koen; Hansen, Dominique

2012-03-01

Chronic heart failure (CHF) patients are frequently rehospitalized within 6 months after an episode of fluid retention. Rehospitalizations are preventable, but this requires an extensive organization of the healthcare system. In this study, we tested whether intensive follow-up of patients through a telemonitoring-facilitated collaboration between general practitioners (GPs) and a heart failure clinic could reduce mortality and rehospitalization rate. One hunderd and sixty CHF patients [mean age 76 ± 10 years, 104 males, mean left ventricular ejection fraction (LVEF) 35 ± 15%] were block randomized by sealed envelopes and assigned to 6 months of intense follow-up facilitated by telemonitoring (TM) or usual care (UC). The TM group measured body weight, blood pressure, and heart rate on a daily basis with electronic devices that transferred the data automatically to an online database. Email alerts were sent to the GP and heart failure clinic to intervene when pre-defined limits were exceeded. All-cause mortality was significantly lower in the TM group as compared with the UC group (5% vs. 17.5%, P = 0.01). The total number of follow-up days lost to hospitalization, dialysis, or death was significantly lower in the TM group as compared with the UC group (13 vs. 30 days, P = 0.02). The number of hospitalizations for heart failure per patient showed a trend (0.24 vs. 0.42 hospitalizations/patient, P = 0.06) in favour of TM. Telemonitoring-facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization, death, or dialysis in CHF patients. These findings need confirmation in a large trial.

[Basic biological characteristics of mesenchymal stem cells derived from bone marrow and human umbilical cord].

PubMed

Han, Zhen-Xia; Shi, Qing; Wang, Da-Kun; Li, Dong; Lyu, Ming

2013-10-01

Bone marrow (BM) and umbilical cord (UC) are the major sources of mesenchymal stem cells for therapeutics. This study was aimed to compare the basic biologic characteristics of bone marrow-derived and umbilical cord derived-mesenchymal stem cells (BM-MSC and UC-MSC) and their immunosuppressive capability in vitro. The BM-MSC and UC-MSC were cultured and amplified under same culture condition. The growth kinetics, phenotypic characteristics and immunosuppressive effects of UC-MSC were compared with those of BM-MSC.Gene chip was used to compare the genes differentially expressed between UC-MSC and BM-MSC. The results showed that UC-MSC shared most of the characteristics of BM-MSC, including morphology and immunophenotype. UC-MSC could be ready expanded for 30 passages without visible changes. However, BM-MSC grew slowly, and the mean doubling time increased notably after passage 6. Both UC-MSC and BM-MSC could inhibit phytohemagglutinin-stimulated peripheral blood mononuclear cell proliferation, in which BM-MSC mediated more inhibitory effect. Compared with UC-MSC, BM-MSC expressed more genes associated with immune response. Meanwhile, the categories of up-regulated genes in UC-MSC were concentrated in organ development and growth. It is concluded that the higher proliferation capacity, low human leukocyte antigen-ABC expression and immunosuppression make UC-MSC an excellent alternative to BM-MSC for cell therapy. The differences between BM-MSC and UC-MSC gene expressions can be explained by their ontogeny and different microenvironment in origin tissue. These differences can affect their efficacy in different therapeutic applications.

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults.

PubMed

Leitner, Gerda C; Vogelsang, Harald

2016-02-06

Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

PubMed Central

Leitner, Gerda C; Vogelsang, Harald

2016-01-01

Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn’s disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient’s disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8+ T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids. PMID:26855808

Online disease management of diabetes: engaging and motivating patients online with enhanced resources-diabetes (EMPOWER-D), a randomized controlled trial.

PubMed

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-05-01

To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational 'nuggets' dispensed electronically by the care team. A1C was the primary outcome variable. Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (-1.32% INT vs -0.66% UC; p<0.001). At 12 months, the differences were not significant (-1.14% INT vs -0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204.

Online disease management of diabetes: Engaging and Motivating Patients Online With Enhanced Resources-Diabetes (EMPOWER-D), a randomized controlled trial

PubMed Central

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-01-01

Objective To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Materials and methods Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational ‘nuggets’ dispensed electronically by the care team. A1C was the primary outcome variable. Results Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (−1.32% INT vs −0.66% UC; p<0.001). At 12 months, the differences were not significant (−1.14% INT vs −0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). Conclusions A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204 PMID:23171659

Counseling African Americans to Control Hypertension: cluster-randomized clinical trial main effects.

PubMed

Ogedegbe, Gbenga; Tobin, Jonathan N; Fernandez, Senaida; Cassells, Andrea; Diaz-Gloster, Marleny; Khalida, Chamanara; Pickering, Thomas; Schwartz, Joseph E

2014-05-20

Data are limited on the implementation of evidence-based multilevel interventions targeted at blood pressure (BP) control in hypertensive blacks who receive care in low-resource primary care practices. Counseling African Americans to Control Hypertension is a cluster-randomized clinical trial in which 30 community health centers were randomly assigned to the intervention condition (IC) or usual care (UC). Patients at the IC sites received patient education, home BP monitoring, and monthly lifestyle counseling, whereas physicians attended monthly hypertension case rounds and received feedback on their patients' home BP readings and chart audits. Patients and physicians at the UC sites received printed patient education material and hypertension treatment guidelines, respectively. The primary outcome was BP control, and secondary outcomes were mean changes in systolic and diastolic BPs at 12 months, assessed with an automated BP device. A total of 1059 patients (mean age, 56 years; 28% men, 59% obese, and 36% with diabetes mellitus) were enrolled. The BP control rate was similar in both groups (IC=49.3% versus UC=44.5%; odds ratio, 1.21 [95% confidence interval, 0.90-1.63]; P=0.21). In prespecified subgroup analyses, the intervention was associated with greater BP control in patients without diabetes mellitus (IC=54.0% versus UC=44.7%; odds ratio, 1.45 [confidence interval, 1.02-2.06]); and small-sized community health centers (IC=51.1% versus UC=39.6%; odds ratio, 1.45 [confidence interval, 1.04-2.45]). A practice-based, multicomponent intervention was no better than UC in improving BP control among hypertensive blacks. Future research on the implementation of behavioral modification strategies for hypertension control in low-resource settings should focus on the development of more efficient and tailored interventions in this high-risk population. http://www.clinicaltrials.gov. Unique identifier: NCT00233220. © 2014 American Heart Association, Inc.

Overweight and obesity in children with newly diagnosed inflammatory bowel disease.

PubMed

Pituch-Zdanowska, Aleksandra; Banaszkiewicz, Aleksandra; Dziekiewicz, Marcin; Łazowska-Przeorek, Izabella; Gawrońska, Agnieszka; Kowalska-Duplaga, Kinga; Iwańczak, Barbara; Klincewicz, Beata; Grzybowska-Chlebowczyk, Urszula; Walkowiak, Jarosław; Albrecht, Piotr

2016-03-01

Determination of overweight and obesity prevalence in children with inflammatory bowel disease (IBD) at the time of diagnosis. This was a multicenter retrospective study. The study group consisted of children with new cases of IBD diagnosed in 2005-2013 according to the Porto criteria. Hospital admission records were reviewed for demographic and clinical characteristics. BMI-for-age and gender percentile charts were used to define overweight as ≥85th BMI percentile and obesity as ≥95th BMI percentile. 675 patients were evaluated: 368 with Crohn's disease (CD) and 307 with ulcerative colitis (UC). Of these, 54.8% were boys and 45.2% were girls. There were no statistically significant differences in age, weight, height and disease activity between the CD and UC patients. The UC patients had higher BMI values than the CD patients. The prevalence of overweight and obesity was higher in the UC than the CD patients (4.89% CI95 2.76-7.93 vs. 2.45% CI95 1.12-4.59 and 8.47% CI95 5.61-12.16 vs. 1.9% CI95 0.77-3.88, respectively); the differences were statistically significant (-2.44% CI95 -5.45 to 0.49 and -6.57% CI95 -10 to -3.1, respectively). The risk of overweight/obesity was 3.5 times higher for patients with UC (OR=0.272, CI95 0.14-0.49, p=0.0004). The prevalence of overweight and obesity in newly diagnosed children with IBD was 8.4% and was higher in patients with UC than in patients with CD. The results of this study have shown that not only malnourished children may suffer from IBD but also children who are overweight or obese at the time of diagnosis. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Yokukansan in the Treatment of Behavioral and Psychological Symptoms of Dementia: An Updated Meta-Analysis of Randomized Controlled Trials.

PubMed

Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao

2016-09-06

Previous clinical studies found that yokukansan has a therapeutic effect on behavioral and psychological symptoms of dementia (BPSD) in dementia patients. To perform an updated meta-analysis of randomized controlled trials (RCTs) testing yokukansan for patients with BPSD. Primary efficacy and safety endpoints were BPSD total scores and all-cause discontinuation, respectively. Secondary outcomes were BPSD subscales, cognitive function scores [Mini-mental state examination (MMSE)], activities of daily living (ADL) scores, discontinuation due to adverse events (AEs), and incidences of AEs. Five RCTs with 381 patients with BPSD were included. Compared with controls [placebo+usual care (UC)], yokukansan significantly decreased BPSD total scores [standardized mean difference (SMD) = -0.32, 95% confidence interval (CI) = -0.53 to -0.11, p = 0.003, I2 = 0%, N = 5 studies, n = 361]. Yokukansan was more efficacious in reducing BPSD subscale scores (delusions: SMD = -0.51, 95% CI = -0.98 to -0.04, hallucinations: SMD = -0.54, 95% CI = -0.96 to -0.12, agitation/aggression: SMD = -0.37, 95% CI = -0.60 to -0.15) than placebo+UC. However, yokukansan was not superior to placebo+UC for BPSD total as well as any subscales scores only in Alzheimer's disease patients. Compared with UC, yokukansan treatment improved ADL scores (SMD = -0.32, 95% CI = -0.62 to -0.01). MMSE scores did not differ between the yokukansan and placebo+UC treatment groups. No significant differences were found in all-cause discontinuation, discontinuation due to AEs, and incidences of AEs between yokukansan and placebo+UC treatments. Our results suggest that yokukansan is beneficial for the treatment of patients with BPSD and is well-tolerated; it was not beneficial for BPSD total and any subscale scores only in Alzheimer's disease patients.

Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients

PubMed Central

Buhner, Sabine; Hahne, Hannes; Hartwig, Kerstin; Li, Qin; Vignali, Sheila; Ostertag, Daniela; Meng, Chen; Hörmannsperger, Gabriele; Braak, Breg; Pehl, Christian; Frieling, Thomas; Barbara, Giovanni; De Giorgio, Roberto; Demir, Ihsan Ekin; Ceyhan, Güralp Onur; Zeller, Florian; Boeckxstaens, Guy; Haller, Dirk; Kuster, Bernhard

2018-01-01

Background & aims The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). Method Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. Results Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin–the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. Conclusion Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to characterise IBS. PMID:29529042

Equally good fixation of cemented and uncemented cups in total trapeziometacarpal joint prostheses. A randomized clinical RSA study with 2-year follow-up.

PubMed

Hansen, Torben Baek; Stilling, Maiken

2013-02-01

Cup failure is a recognized problem in total trapeziometacarpal (TM) joint prostheses; it may be related to poor fixation, which can be revealed by radiostereometric analysis (RSA). We compared the early implant migration of cemented trapezium cups to that of uncemented screw cups. In a prospective, parallel-group, randomized patient-blinded clinical trial, we included 32 hands in 28 patients (5 males) with a mean age of 58 (40-77) years and with Eaton stage-2 or -3 osteoarthritis of the trapeziometacarpal joint. Patients were randomized to surgery with a cemented DLC all-polyethylene cup (C) (n = 16) or an uncemented hydroxyapatite-coated chrome-cobalt Elektra screw cup (UC) (n = 16). Uncemented cups were inserted without threading of the bone. Stereoradiographs for evaluation of cup migration (primary effect size) and DASH and pain scores were obtained during 2 years of follow-up. The 2-year total translation (TT) was similar (p = 0.2): 0.24 mm (SD 0.10) for the C (n = 11) and 0.19 mm (SD 0.16) for the UC (n = 11). Variances were similar (p = 0.4). Judged by RSA, 2 UC cups and 1 C cup became loose (TT > 1 mm). Both UC cups were found to be loose at revision. Grip strength, pain, and DASH scores were similar between groups at all measurement points. Early implant fixation and clinical outcome were equally good with both cup designs. This is the first clinical RSA study on trapezium cups, and the method appears to be clinically useful for detection of loose implants.

Applicability, limitations and downstream impact of echocardiography utilization based on the Appropriateness Use Criteria for transthoracic and transesophageal echocardiography.

PubMed

Alqarqaz, Mohammad; Koneru, Jayanth; Mahan, Meredith; Ananthasubramaniam, Karthik

2012-12-01

To evaluate impact of echocardiography on patient management based on published transthoracic echocardiography (TTE) Appropriate Use Criteria (AUC). A prospective analysis of 170 consecutive outpatients who underwent TTE over a period of 2 months. Echo studies were classified into appropriate (A), inappropriate (I), or uncertain (U) based on the 2007/2011 AUC. A fourth group of studies which were not addressed by the 2007 AUC and therefore have unclassifiable category (UC) were also included in the analysis. The impact of AUC categorized echo results on patient management were evaluated by review of patient records in the ensuing 2 months. Based on 2007 AUC, 77% (131/170) were A, 9% were I, and 14% were UC category. Echo studies classified as A were more likely to be associated with new and major findings, (P = 0.034) and (P = 0.028) respectively when compared to all other studies. Furthermore, patient care intervention as defined in the study protocol was significantly associated with A studies as opposed to I and UC studies (P = 0.004). A studies were also more likely to have an impact on patient management when compared to other studies (P = 0.022). When studies were re-evaluated based on the 2011 AUC, all prior UC studies were now included in the U group in the new AUC of 2011, and there was no change in A or I study classification. This study demonstrates that the 2007/2011 AUC are helpful in evaluating practice patterns in a majority of outpatients undergoing TTE. Implementing AUC have a direct clinical impact as A studies are significantly more likely to reveal new and major findings, and more likely to result in a patient care intervention based on the echo findings.

Suboptimal vitamin K status despite supplementation in children and young adults with cystic fibrosis.

PubMed

Dougherty, Kelly A; Schall, Joan I; Stallings, Virginia A

2010-09-01

For children and adolescents with cystic fibrosis (CF) and pancreatic insufficiency, the efficacy of routine vitamin K supplementation to normalize vitamin K status remains unclear. This study examined and determined predictors of vitamin K status in subjects aged 8-25 y with CF and pancreatic insufficiency taking various vitamin K supplements. In 97 subjects, serum 25-hydroxyvitamin D [25(OH)D], dietary intake, vitamin K supplement intake, and vitamin K statusmdashdetermined on the basis of the percentage of serum undercarboxylated osteocalcin (%ucOC; sufficient: lt 20%) and plasma proteins induced by vitamin K absence-factor II (PIVKA-II; n = 60; sufficient: le 2 microg/L)mdashwere assessed. The vitamin K supplementation groups were as follows: lt 150 microg/d (low; multivitamins or no supplement), 150-999 microg/d (middle; CF-specific vitamins), and ge 1000 microg/d (high; mephyton). %ucOC values were compared with 140 healthy subjects aged 6-21 y. In subjects with CF, the median (range) %ucOC was 35% (3%, 76%) and the median (range) for PIVKA-II was 2 (0, 42) micro g/L. Subjects with CF had a higher %ucOC with low [45% (10%, 76%)] and medium [41% (3%, 66%)] supplement intakes but not with a high supplement intake [16% (4%, 72%)] compared with healthy subjects [23% (0%, 43%); both P lt 0.05]. Supplementation group for males and females and 25(OH)D and age for males were significant predictors of vitamin K status. Vitamin K status was often suboptimal despite routine supplementation. Only subjects taking high-dose vitamin K achieved a status similar to healthy subjects, and only the vitamin K supplementation dose predicted vitamin K status for males and females. These data suggest that higher doses of vitamin K are required.

Meta-analysis using individual patient data: efficacy and durability of topical alicaforsen for the treatment of active ulcerative colitis.

PubMed

Vegter, S; Tolley, K; Wilson Waterworth, T; Jones, H; Jones, S; Jewell, D

2013-08-01

The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry. To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features. Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests. Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious. This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC. © 2013 John Wiley & Sons Ltd.