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Miyazaki, S., and R. J. Korsch. "COALBED METHANE RESOURCES IN THE PERMIAN OF EASTERN AUSTRALIA AND THEIR TECTONIC SETTING." APPEA Journal 33, no. 1 (1993): 161. http://dx.doi.org/10.1071/aj92013.
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The Bowen and Sydney Basins in eastern Australia contain vast coal resources which provide a source for coalbed methane. Through studies of the spatial and temporal distribution of the sedimentary packages, the structural geometry and tectonic setting of the sedimentary packages, and the maturation and burial history, the Australian Geological Survey Organisation (AGSO) is mapping the distribution and structural styles of the sources of methane, in particular, the Late Permian coal measures. AGSO's results from the Bowen Basin show at least two distinctly different structural styles of potential targets for coalbed methane drainage: on the Comet Ridge, the Permian coal measures are essentially subhorizontal and tectonically undisturbed, whereas in the western Taroom Trough, the coal measures are folded into a series of anticlines, each of which occurs above a thrust fault which in turn forms part of an imbricate thrust fan. Both of these styles occur at depths of less than 1000 m.Calculations by the Bureau of Resource Sciences (BRS) indicate that the inferred coalbed methane resources-in-place are 62 trillion cubic feet (1760 billion m3) for Australia, in which the Bowen and Sydney Basins are currently the only potential provinces of coalbed methane. The low permeability of the coal seams hinders attempts to utilise this vast amount of energy resources.Further exploration is necessary to delineate commercially feasible areas. This delineation is the only process that will be able to determine demonstrated coalbed methane resources.
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Oliphant, Andrew J., Richard C. A. Hindmarsh, Nicolas J. Cullen, and Wendy Lawson. "Microclimate and mass fluxes of debris-laden ice surfaces in Taylor Valley, Antarctica." Antarctic Science 27, no. 1 (September 23, 2014): 85–100. http://dx.doi.org/10.1017/s0954102014000534.
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AbstractThis study investigates the microclimate and hydrology of debris-laden ice surfaces in the Taylor Valley, Antarctica, in early summer, focusing on the onset of melt. Measurements of energy and mass fluxes were made on an outwash fan and in moraines near the terminus of Taylor Glacier. The surface microclimate was strongly controlled by absorbed solar radiation, with a low albedo of 0.17. Seasonal warming of the substrate led to an abrupt shift in thermal and hydrological patterns as temperatures exceeded freezing point. Within a week the Bowen ratio switched from 2.05 to 0.48 and mass losses to the atmosphere increased four-fold from 0.39 to 1.6 mm d-1. Melt onset also produced complex ground temperature patterns with strong diurnal damping below the freezing front. These patterns were caused by phase changes in the freezing front, coupled with an abundant water supply from local runoff. Of secondary importance to the surface energy balance and mass fluxes was the effect of local winds on boundary layer characteristics. This resulted in larger mass losses during the more turbulent, warmer and drier down-valley flows.
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Newton, Kim, Vishva M. Dixit, and Nobuhiko Kayagaki. "Dying cells fan the flames of inflammation." Science 374, no. 6571 (November 26, 2021): 1076–80. http://dx.doi.org/10.1126/science.abi5934.
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Inflammatory processes that recruit leukocytes to injured or infected tissues are crucial for tissue repair and the elimination of pathogens. However, excessive or chronic inflammation promotes tissue damage and disease, as in arthritis, atherosclerosis, inflammatory bowel disease, and COVID-19. Intracellular constituents released from dying cells are among the stimuli that trigger proinflammatory gene expression programs in innate immune cells. We explore how programmed cell death mechanisms—apoptosis, necroptosis, and pyroptosis—may contribute to inflammatory disease. We discuss inhibition of cell death as a potential therapeutic strategy, focusing on the targets RIPK1 (receptor interacting serine/threonine kinase 1), NLRP3 (NLR family pyrin domain containing 3), and GSDMD (gasdermin D) as important mediators of lytic cell death. We also consider the potential benefits of limiting membrane rupture rather than cell death by targeting NINJ1.
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Wang, Han, Huiying Sun, Bilin Liang, Fang Zhang, Fan Yang, Bowen Cui, Lixia Ding, et al. "Abstract 6213: Chromatin accessibility landscape of pediatric high-risk B-cell acute lymphoblastic leukemia." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6213. http://dx.doi.org/10.1158/1538-7445.am2022-6213.
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Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Although overall cure rate has exceeded 90%, the prognosis of high-risk B-ALL remains poor. Genome sequencing studies have revealed key genetic aberrations in B-ALL. But driver remains unclear in 8% of B-ALL for leukemogenesis, and 40% of high-risk B-ALL for drug resistance. Epigenetic mechanisms contributing to leukemia have recently been recognized, including histone modification and methylation. To date, a comprehensive landscape of chromatin accessibility in B-ALL is still lacking. Here, we performed Assays for Transposase Accessible Chromatin using sequencing (ATAC-seq) on a total of 61 high-risk B-ALLs treated at Shanghai Children’s Medical Center, including major B-ALL subtypes. We generated 144 high quality chromatin accessibility profiles from 79 tumors, including 18 diagnosis-relapse paired tumors as well as 11 diagnosis and 32 relapsed tumors. We observed significantly higher chromatin accessibility in B-ALL as compared to normal B-cells. Functional chromatin state annotation showed a median of 27.1% open chromatin regions (OCRs) in B-ALL were constituted from quiescent regions that were absent for known histone modifications, indicating unveiled role of quiescent regions in B-ALL. We further investigated the allelic imbalanced chromatin accessibility in 32 B-ALL with matched ATAC-seq and whole genome sequencing data. Unexpectedly, we found a median of 10.8% of OCRs showed imbalanced accessibility between two heterozygous alleles. Moreover, the adjacent imbalanced OCRs tend to be in the same topologically associating domain, suggesting the transcription regulation from chromatin accessibility was constrained within 3-D genome architecture. We next looked into the OCRs among B-ALL subtypes. Consistent with the regulatory role of chromatin accessibility on gene transcription, we found subtype specific pattern of OCRs in B-ALL, with open regions from enhancer and bivalent chromatin states showed more power in subtype discrimination. A total of 15516 out of 765788 (2.03%) peaks were identified as subtype specific OCRs. Motif analysis associated these regions to 212 transcription factors (TFs). Consistently, genes regulated by these TFs also exhibited subtype specific expression. Finally, we analyzed differences in OCRs between diagnosis (D) and relapse (R) in each B-ALL subtype. Only 2.44% D-R differential peaks were shared between any two subtypes, suggesting subtype specific role of chromatin accessibility in relapse. Potential target genes were further identified with quantitative trait loci analysis. With data from DepMap project, we verified that the expression of the target genes identified was associated with drug response. These data unveiled potential role of chromatin accessibility in high-risk B-ALL and the treatment response of this malignancy. Citation Format: Han Wang, Huiying Sun, Bilin Liang, Fang Zhang, Fan Yang, Bowen Cui, Lixia Ding, Ronghua Wang, Yanjing Tang, Jianan Rao, Wenting Hu, Shuang Zhao, Wenyan Wu, Benshang Li, Jingyan Tang, Shuhong Shen, Yu Liu. Chromatin accessibility landscape of pediatric high-risk B-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6213.
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Wolter, A., D. L. Munz, and V. Ivančević. "Nonspecific bowel activity in imaging inflammation with Tc-99m labelled monoclonal anti-NCA-90 Fab’ fragment MN3." Nuklearmedizin 40, no. 03 (2001): 71–74. http://dx.doi.org/10.1055/s-0038-1623873.
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Summary Aim: Since the Tc-99m labelled monoclonal anti-NCA 90 granulocyte antibody Fab’ fragment MN3 (MN3 Fab’) might be of interest for imaging abdominal inflammation which could be hampered by nonspecific bowel activity, we prospectively investigated the appearance of bowel activity in MN3 Fab’ imaging. Methods: Eighty consecutive patients (age range 12-85 years) referred for suspected nonabdominal, mostly musculoskeletal infection, were included. Abdominal inflammation was excluded clinically and there were no signs of inflammatory bowel disease in the patients’ histories. One, 5, and 24 hours after intravenous injection of up to 1.1 GBq of MN3 Fab’ planar images of the abdomen were performed. Bowel activity was graded visually using a 5-point scale. Results: The one (N = 80), 5 (N = 79), and 24 (N = 52) hour images revealed 46 (10%), 162 (34%), and 173 (55%) accumulating bowel segments, respectively, in 37 (46%), 69 (87%), and 52 (100%) patients. The mean intensity score per accumulating segment was 1.1,1.8 and 2.7 (p = 0), respectively. Relative frequencies of appearance of the small intestine were 38%, 57%, and 21%, ileocaecal region 6%, 53%, and 48%, ascending colon 5%, 67%, and 89%, transverse colon 1%, 9%, and 69%, descending colon 8%,15 %, and 67%, and rectosigmoid 0%, 4%, and 38%, respectively. Follow-up investigations in 13 patients revealed diverging uptake patterns. Conclusion: Nonspecific bowel activity is often present in the early and almost always and more intense, in the delayed images. Early imaging at one hour after administration seems feasible, but a loss in sensitivity has to be considered. Thus, nonspecific bowel activity can be anticipated to be a pitfall in imaging abdominal inflammation with MN3 Fab’.
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Chen, L., X. J. Liu, A. L. Yang, and R. Dai. "Flow performance of highly loaded axial fan with bowed rotor blades." IOP Conference Series: Materials Science and Engineering 52, no. 4 (December 20, 2013): 042005. http://dx.doi.org/10.1088/1757-899x/52/4/042005.
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Fu, Chen, Li Shaobin, Su Jiexian, and Wang Zhongqi. "Experimental Study of Bowed-twisted Stators in an Axial Transonic Fan Stage." Chinese Journal of Aeronautics 22, no. 4 (August 2009): 364–70. http://dx.doi.org/10.1016/s1000-9361(08)06112-0.
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Pipek, Barbora. "Monoclonal antibodies in pregnant women with inflammatory bowel disease." Klinická farmakologie a farmacie 34, no. 2 (July 16, 2020): 74–77. http://dx.doi.org/10.36290/far.2020.015.
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Li, Shaobin, Jiexian Su, and Zhongqi Wang. "Application of high-turning bowed compressor stator to redesign of highly loaded fan stage." Frontiers of Energy and Power Engineering in China 2, no. 4 (July 4, 2008): 534–40. http://dx.doi.org/10.1007/s11708-008-0066-6.
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Huang, Enliang, Shengfeng Zhao, Jianbo Gong, Xingen Lu, and Junqiang Zhu. "Numerical investigation of the bowed stator effects in a transonic fan at low Reynolds number." Journal of Thermal Science 26, no. 1 (January 18, 2017): 25–29. http://dx.doi.org/10.1007/s11630-017-0905-z.
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Liu, Lina, Xueting Cai, Jing Yan, Yi Luo, Ming Shao, Yin Lu, Zhiguang Sun, and Peng Cao. "In VivoandIn VitroAntinociceptive Effect ofFagopyrum cymosum(Trev.) Meisn Extracts: A Possible Action by Recovering Intestinal Barrier Dysfunction." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/983801.
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Fagopyrum cymosum(Trev.) Meisn (Fag) is a herb rhizome which has been widely used to treat diseases. To investigate the effects and mechanisms of the Fag on irritable bowel syndrome (IBS),in vivoneonatal pups maternal separation (NMS) combined with intracolonic infusion of acetic acid (AA) was employed to establish IBS rat models. Fag reduced their visceral hyperalgesia and the whole gut permeability, ameliorated colonic mucosa inflammation and injury, and upregulated the expression of decreased tight junction proteins (TJs) of claudin-1, occludin, and ZO-1 (except ZO-2) in colonic epithelium. Caco-2 monolayer cells were incubated with TNF-αand IFN-γ in vitroto establish an epithelial barrier dysfunction model whose transepithelial electrical resistance (TER) depended more on dose of Fag than that of the controls, and whose TJs levels were lower than those of the controls. Fag upregulated the NP-40 insoluble and soluble components of the four TJs markedly in a dose-dependent manner. These data suggest that Fag alleviated the hyperalgesia of IBS rats by reducing intestinal inflammation and enhancing mucosal epithelial function after regulating the structure and function of TJs.
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Ray, Upasana, Deok-Beom Jung, Ling Jin, Yinan Xiao, Subramanyam Dasari, Sayantani Sarkar Bhattacharya, Prabhu Thirusangu, et al. "Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer." Cancer Research 82, no. 6 (March 15, 2022): 1038–54. http://dx.doi.org/10.1158/0008-5472.can-21-0622.
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Abstract Dissemination of ovarian cancer cells can lead to inoperable metastatic lesions in the bowel and omentum that cause patient death. Here we show that LRRC15, a type-I 15-leucine–rich repeat-containing membrane protein, highly overexpressed in ovarian cancer bowel metastases compared with matched primary tumors and acts as a potent promoter of omental metastasis. Complementary models of ovarian cancer demonstrated that LRRC15 expression leads to inhibition of anoikis-induced cell death and promotes adhesion and invasion through matrices that mimic omentum. Mechanistically, LRRC15 interacted with β1-integrin to stimulate activation of focal adhesion kinase (FAK) signaling. As a therapeutic proof of concept, targeting LRRC15 with the specific antibody–drug conjugate ABBV-085 in both early and late metastatic ovarian cancer cell line xenograft models prevented metastatic dissemination, and these results were corroborated in metastatic patient-derived ovarian cancer xenograft models. Furthermore, treatment of 3D-spheroid cultures of LRRC15-positive patient-derived ascites with ABBV-085 reduced cell viability. Overall, these data uncover a role for LRRC15 in promoting ovarian cancer metastasis and suggest a novel and promising therapy to target ovarian cancer metastases. Significance: This study identifies that LRRC15 activates β1-integrin/FAK signaling to promote ovarian cancer metastasis and shows that the LRRC15-targeted antibody–drug conjugate ABBV-085 suppresses ovarian cancer metastasis in preclinical models.
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Antonioli, Luca, Carolina Pellegrini, Matteo Fornai, Laura Benvenuti, Vanessa D’Antongiovanni, Rocchina Colucci, Lorenzo Bertani, et al. "Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation." International Journal of Molecular Sciences 22, no. 12 (June 13, 2021): 6325. http://dx.doi.org/10.3390/ijms22126325.
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Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.
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Lemire, Sarah, Oana-Maria Thoma, Lucas Kreiss, Simon Völkl, Oliver Friedrich, Markus F. Neurath, Sebastian Schürmann, and Maximilian J. Waldner. "Natural NADH and FAD Autofluorescence as Label-Free Biomarkers for Discriminating Subtypes and Functional States of Immune Cells." International Journal of Molecular Sciences 23, no. 4 (February 20, 2022): 2338. http://dx.doi.org/10.3390/ijms23042338.
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Immune cell activity is a major factor for disease progression in inflammatory bowel diseases (IBD). Classifying the type and functional state of immune cells is therefore crucial in clinical diagnostics of IBD. Label-free optical technologies exploiting NADH and FAD autofluorescence, such as multiphoton microscopy, have been used to describe tissue morphology in healthy and inflamed colon samples. Nevertheless, a strategy for the identification of single immune cell subtypes within the tissue is yet to be developed. This work aims to initiate an understanding of autofluorescence changes depending on immune cell type and activation state. For this, NADH and FAD autofluorescence signals of different murine immune cell subtypes under native conditions, as well as upon in vitro stimulation and cell death, have been evaluated. Autofluorescence was assessed using flow cytometry and multiphoton microscopy. Our results reveal significantly increased NADH and FAD signals in innate immune cells compared to adaptive immune cells. This allowed identification of relative amounts of neutrophils and CD4+ T cells in mixed cell suspensions, by using NADH signals as a differentiation marker. Furthermore, in vitro stimulation significantly increased NADH and FAD autofluorescence in adaptive immune cells and macrophages. Cell death induced a significant drop in NADH autofluorescence, while FAD signals were hardly affected. Taken together, these results demonstrate the value of autofluorescence as a tool to characterize immune cells in different functional states, paving the way to the label-free clinical classification of IBD in the future.
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PAI, Chih-Hung, Kuo-Min KO, and Troy SANTOS. "A Study of the Effect of Service Recovery on Customer Loyalty Based On Marketing Word Of Mouth in Tourism Industry." Revista de Cercetare si Interventie Sociala 64 (March 6, 2019): 74–84. http://dx.doi.org/10.33788/rcis.64.6.
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Akamavi, R K., Mohamed, E., Pellmann, K., & Xu, Y. (2015). Key determinants of passenger loyalty in the low-cost airline business. Tourism Management, 46, 528-545. Baldus, B.J., Voorhees, C., & Calantone, R. (2015). Online brand community engagement: Scale development and validation. Journal of Business Research, 68(5), 978-985. Boo, H.V. (2017). Service Environment of Restaurants: Findings from the youth customers. Journal of Asian Behavioural Studies, 2(2), 67-77. Bowen, T.J., & Chen, S.L. (2015). Transitioning Loyalty Programs: A Commentary on the Relationship Between Customer Loyalty & Customer Satisfaction. International Journal of Contemporary Hospitality Management, 27(3), 415-430. Casidy, R., & Shin, H. (2015). The effects of harm directions and service recovery strategies on customer forgiveness and negative word-of-mouth intentions. Journal of Retailing and Consumer Services, 27, 103-112. Chang, J.H. (2017). The role of relationship on time and monetary compensation. The Service Industries Journal, 37, 915-935. Fan, A., Mattila, A.S., & Zhao, X. (2015). How does social distance impact customers’ complaint intentions? A cross-cultural examination. International Journal of Health Policy and Management, 47, 35-42. Gohary, A., Hamzelu, B., & Alizadeh, H. (2016). Please explain why it happened! How perceived justice and customer involvement affect post co-recovery evaluations: a study of Iranian online shoppers. Journal of Retailing and Consumer Services, 31, 127-142. Guo, L., Lotz, S.L., Tang, C., & Gruen, T.W. (2015). The role of perceived control in customer value cocreation and service recovery evaluation. Journal of Service Research, 19(1), 39-56. Heidenreich, S., Wittkowski, K., Handrich, M., & Falk, T. (2015). The dark side of customer co-creation: exploring the consequences of failed co-created services. The Journal of the Academy of Marketing Science, 43(3), 279-296. Hsu, C.L., & Lin, J.C.C. (2016). Effect of perceived value and social influences onmobile app stickiness and in-app purchase intention.Technological Forecasting and Social Change, 108, 42-53. Kashif, M., Zarkada, A., & Ramayah, T. (2016).The impact of attitude, subjective norms, and perceived behavioural control on managers’ intentions to behave ethically. Total Quality Management & Business Excellence, 29(5-6), 1-21. Li, M., Qiu, S.C., & Liu, Z., (2016). The Chinese way of response to hospitality service failure: The effects of face and guanxi. International Journal Hospital Management, 57, 18-29. Liu, S.Q., & Mattila, A.S. (2015). “I Want to Help” versus “I Am Just Mad” how affective commitment influences customer feedback decisions. Cornell Hospitality Quarterly, 56(2), 213-222. Oman, B., Pepur, M., & Arneric, J. (2016). The impact of service quality and sport-team identification on the repurchase intention. Journal of Contemporary Management Issues, 21(1), 19-46. Ozuem, W., Patel, A., Howell, K.E. & Lancaster, G. (2016). An Exploration of Consumers' Response to Online Service Recovery Initiatives. International Journal of Market Research, 59(1), 97-115. Park, J., & Ha, S. (2016). Co-creation of service recovery: Utilitarian and hedonic value and post-recovery responses. Journal of Retailing and Consumer Services, 28, 310-316. Rezaei, S., Shahijan, M.K., Amin, M., & Ismail, W.K.W. (2016). Determinants ofapp stores continuance behavior: A pls path modellingapproach. Journal of Internet Commerce, 15(4), 408-440. Sengupta, S.A., Balaji, M., & Krishnan, B.C. (2015). How customers cope with service failure? A study of brand reputation and customer satisfaction. Journal of Business Research, 68(3), 665-674. Sloan, S., Bodey, K., & Gyrd-Jones, R. (2015). Knowledge sharing in online brand communities. Qualitative Market Research: An International Journal, 18(3), 320-345. Tan, C., Benbasat, I. & Cenfetelli, R.T. (2016). An Exploratory Study of the Formation and Impact of Electronic Service Failures. MIS Quarterly, 40(1), 1-31. Van Vaerenbergh, Y., & Orsingher, C. (2016). Service Recovery: An Integrative Framework and Research Agenda. The Academy of Management Perspectives, 30(3), 328-346. Varela, J.C.S., Svensson, G., Brambilla, F.R., & Oliveros, M.E.G. (2015) Perceived Justice & Emotions in a Negative Service Encounter: A Latin American Perspective. In: Kubacki K. (eds). Ideas in Marketing: Finding the New and Polishing the Old. Developments in Marketing Science: Proceedings of the Academy of Marketing Science. Cham: Springer. Vyas, V. & Raitani, S. (2015). A Study of the Impact of Relationship Marketing on Cross-Buying. Journal of Relationship Marketing, 14(2), 79-108. Weber, K., Sparks, B., & Hsu, C.H. (2016). The effects of acculturation, social distinctiveness, and social presence in a service failure situation. International Journal Hospital Management, 56, 44-55. Wu, J., Huang, L., Zhao, J.L., & Hua, Z. (2015).The deeper, the better? Effect of online brand community activity on customer purchase frequency. Information & Management, 52(7), 813-823. Yang, A., Chen, Y., & Huang, Y. (2017). Enhancing customer loyalty in tourism services: the role of customer-company identification and customer participation. Asia Pacific Journal of Tourism Research, 22(7), 735-746. Zhang, H., Zhang, K.Z., Lee, M.K., & Feng, F. (2015). Brand loyalty in enterprise microblogs: Influence of community commitment, IT habit, and participation. Information Technology & People, 28(2), 304-326.
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Oncel, Sema, Rashmi Gupta, Qinggang Wang, and Marc D. Basson. "ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase." Cells 10, no. 4 (April 15, 2021): 908. http://dx.doi.org/10.3390/cells10040908.
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Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.
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Zeng, Jie, Jin Peng, Hua Jiang, Pengchi Deng, Kexun Li, Daolin Long, and Kai Wang. "Establishment of an early diagnosis model of colon cancerous bowel obstruction based on 1H NMR." PLOS ONE 17, no. 8 (August 16, 2022): e0266730. http://dx.doi.org/10.1371/journal.pone.0266730.
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Objective To prospectively establish an early diagnosis model of acute colon cancerous bowel obstruction by applying nuclear magnetic resonance hydrogen spectroscopy(1H NMR) technology based metabolomics methods, combined with machine learning. Methods In this study, serum samples of 71 patients with acute bowel obstruction requiring emergency surgery who were admitted to the Emergency Department of Sichuan Provincial People’s Hospital from December 2018 to November 2020 were collected within 2 hours after admission, and NMR spectroscopy data was taken after pretreatment. After postoperative pathological confirmation, they were divided into colon cancerous bowel obstruction (CBO) group and adhesive bowel obstruction (ABO) control group. Used MestReNova software to extract the two sets of spectra bins, and used the MetaboAnalyst5.0 website to perform partial least square discrimination (PLS-DA), combining the human metabolome database (HMDB) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find possible different Metabolites and related metabolic pathways. Results 22 patients were classified as CBO group and 30 were classified as ABO control group. Compared with ABO group, the level of Xanthurenic acid, 3-Hydroxyanthranilic acid, Gentisic acid, Salicyluric acid, Ferulic acid, Kynurenic acid, CDP, Mandelic acid, NADPH, FAD, Phenylpyruvate, Allyl isothiocyanate, and Vanillylmandelic acid increased in the CBO group; while the lecel of L-Tryptophan and Bilirubin decreased. There were significant differences between two groups in the tryptophan metabolism, tyrosine metabolism, glutathione metabolism, phenylalanine metabolism and synthesis pathways of phenylalanine, tyrosine and tryptophan (all P<0.05). Tryptophan metabolism pathway had the greatest impact (Impact = 0.19). The early diagnosis model of colon cancerous bowel was established based on the levels of six metabolites: Xanthurenic acid, 3-Hydroxyanthranilic acid, Gentisic acid, Salicylic acid, Ferulic acid and Kynurenic acid (R2 = 0.995, Q2 = 0.931, RMSE = 0.239, AUC = 0.962). Conclusion This study firstly used serum to determine the difference in metabolome between patients with colon cancerous bowel obstruction and those with adhesive bowel obstruction. The study found that the metabolic information carried by the serum was sufficient to discriminate the two groups of patients and provided the theoretical supporting for the future using of the more convenient sample for the differential diagnosis of patients with colon cancerous bowel obstruction. Quantitative experiments on a large number of samples were still needed in the future.
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Corredor, Julissa, Fang Yan, Christopher C. Shen, Wei Tong, Sutha K. John, Guinn Wilson, Robert Whitehead, and D. Brent Polk. "Tumor necrosis factor regulates intestinal epithelial cell migration by receptor-dependent mechanisms." American Journal of Physiology-Cell Physiology 284, no. 4 (April 1, 2003): C953—C961. http://dx.doi.org/10.1152/ajpcell.00309.2002.
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Altered mucosal integrity and increased cytokine production, including tumor necrosis factor (TNF), are the hallmarks of inflammatory bowel disease (IBD). In this study, we addressed the role of TNF receptors (TNFR) on intestinal epithelial cell migration in an in vitro wound closure model. With mouse TNFR1 or TNFR2 knockout intestinal epithelial cells, gene transfection, and pharmacological inhibitors, we show a concentration-dependent receptor-mediated regulation of intestinal cell migration by TNF. A physiological TNF level (1 ng/ml) enhances migration through TNFR2, whereas a pathological level (100 ng/ml) inhibits wound closure through TNFR1. Increased rate of wound closure by TNFR2 or inhibition by TNFR1 cannot be explained by either increased proliferation or apoptosis, respectively. Furthermore, inhibiting Src tyrosine kinase decreases TNF-induced focal adhesion kinase (FAK) tyrosine phosphorylation and cellular migration. We therefore conclude that TNFR2 activates a novel Src-regulated pathway involving FAK tyrosine phosphorylation that enhances migration of intestinal epithelial cells.
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Ganda Mall, John-Peter, Maite Casado-Bedmar, Martin E. Winberg, Robert J. Brummer, Ida Schoultz, and Åsa V. Keita. "A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn’s Disease and Control Subjects." Inflammatory Bowel Diseases 24, no. 1 (December 19, 2017): 166–78. http://dx.doi.org/10.1093/ibd/izx002.
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Abstract Background Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn’s disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro. Methods Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs. Results β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls. Conclusions We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.
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Atkins, Jen. "The new normal: Activist handmaids and cosplay choreographies in Trump’s America." European Journal of American Culture 41, no. 2 (June 1, 2022): 187–208. http://dx.doi.org/10.1386/ejac_00071_1.
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Though in production before Trump’s election, streaming service Hulu’s serial adaption of The Handmaid’s Tale premiered to acclaim in April 2017. Audiences denoted parallels between ultra-conservative, fictional Gilead and the United States’ own political climate. In response to women’s issues in particular, international groups utilized the central Handmaid’s Tale image as their costume ‐ a crimson robe, a white ‘wing’ bonnet ‐ then occupied public spaces to protest silently. WIRED dubbed the garb the ‘Viral Protest Uniform of 2019’, while online lifestyle/culture magazine Quartz named it the ‘ultimate symbol of women’s rights’. The activists’ presence is critical to their work. Mirroring their fictional handmaid counterparts, cosplay activists employ a bowed head, a slow steady gait and equidistant spacing to evoke the harrowing restrictions Gilead’s women face ‐ what ideologically fervent aunts call Gilead’s ‘new normal’. Activists’ physicality generates a doubleness: as they perform submissiveness and literally fall into line, they also craft solidarity via resistance. Likewise, the fiction hints at revolution, which may be why, in the #MeToo and Time’s Up era, the emancipatory potential of cosplay choreographies steeped in popular culture offer their own ‘new normal’, disrupting patriarchal paradigms modelled by the Trump administration while offering feminist fan activism as strategies that promote creative, inclusive political action.
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Russell, Thomas B., and Somaiah Aroori. "How we do it: Laparoscopic cholecystectomy in patients with severe obesity." Turkish Journal of Surgery 37, no. 4 (December 1, 2021): 413–16. http://dx.doi.org/10.47717/turkjsurg.2021.5452.
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The number of patients with obesity is set to rise, as is the proportion with severe obesity. These patients are a high-risk subgroup who present addi- tional challenges to the surgeon when performing laparoscopic cholecystectomy. It is important that all surgeons who perform this procedure have a safe strategy they can revert to. This article outlines our approach. After obtaining pneumoperitoneum via a supra-umbilical incision, we advise placing a fascial suture before proceeding with the operation. This allows for high-quality closure, reduces the incidence of incisional hernia, and reduces the risk of inadvertent bowel injury. We also advise the repositioning of the patient on the operating table prior to port placement such that an ergonomic set-up can be achieved. In addition to standard ports, we use an additional twelve-millimetre port in the left upper quadrant. A fan retractor can be inserted via this port and used to gently retract the duodenum inferiorly. This provides adequate exposure for Calot’s dissection and arguably reduces the risk of injury to a fatty liver. This technique can also be used in non-obese patients in whom Calot’s dissection is particularly challenging, for instance in those who undergo delayed cholecystectomy.
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Iordache, Miorita Melina, Cristina Tocia, Mariana Aschie, Andrei Dumitru, Mihaela Manea, Georgeta Camelia Cozaru, Lucian Petcu, Sabina E. Vlad, Eugen Dumitru, and Anca Chisoi. "Intestinal Permeability and Depression in Patients with Inflammatory Bowel Disease." Journal of Clinical Medicine 11, no. 17 (August 30, 2022): 5121. http://dx.doi.org/10.3390/jcm11175121.
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Depression is a global health problem that requires an early and accurate diagnosis to ensure quick access to appropriate treatment. Among multiple psychopathological paths, recent attention has focused on analysing the brain–gut–microbiota axis. The intestinal barrier plays a key role, and dysfunctions occurring at this level have implications for mental health. The aim of the present study was to investigate the role of intestinal permeability biomarkers, i.e., calprotectin, zonulin, lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FAB), in relation to depression in patients with inflammatory bowel disease (IBD). This is the first study of this kind taking place in Romania, Eastern Europe, with an emphasis on patients with Crohn’s disease and ulcerative colitis. The correlations identified between depression and calprotectin and depression and LBP have the potential to shed light on the process of rapid diagnosis of depression with the help of biomarkers. Since depression is correlated with a decrease in the quality of life in patients with IBD, the need for access to appropriate treatments must be urgent.
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Jones, B. D., N. Ghori, and S. Falkow. "Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches." Journal of Experimental Medicine 180, no. 1 (July 1, 1994): 15–23. http://dx.doi.org/10.1084/jem.180.1.15.
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Salmonella species are known to initiate infection of mammalian hosts by penetrating the intestinal epithelium of the small bowel. These bacteria preferentially interact with Peyer's patches which are collections of lymphoid follicles making up the gut-associated lymphoid tissue. We infected murine ligated intestinal loops with invasive and noninvasive Salmonella typhimurium strains for 30, 60, 120, and 180 min and examined the infected tissue by transmission electron microscopy. Within 30 min, we found that invasive S. typhimurium exclusively entered M cells found within the follicle-associated epithelium (FAE) of the Peyer's patches. Initially, interactions between invasive bacteria and enterocytes adjacent to the M cells were not found. Invasion of M cells was associated with the ability of the bacteria to invade tissue culture cells. S. typhimurium mutants, which were noninvasive for tissue culture cells, could not be found in ligated loops associated with M cells or enterocytes after incubations of 30, 60, 120, or 180 min. At 60 min, internalized invasive S. typhimurium were cytotoxic for the M cells. Destruction of an M cell formed a gap in the FAE which allowed organisms to invade enterocytes adjacent to the dead cell. Later in the infection process (120 and 180 min), the presence of bacteria beneath the FAE correlated with changes in the cytoarchitecture of the lymphoid follicle. In addition, replicating Salmonella began to enter both the apical and basolateral surfaces of enterocytes adjacent to infected M cells.
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Jhaveri, Pavan M., Bin S. Teh, Arnold C. Paulino, Mindy J. Smiedala, Bridget Fahy, Walter Grant, John McGary, and E. Brian Butler. "Helical Tomotherapy Significantly Reduces Dose to Normal Tissues When Compared to 3D-CRT for Locally Advanced Rectal Cancer." Technology in Cancer Research & Treatment 8, no. 5 (October 2009): 379–85. http://dx.doi.org/10.1177/153303460900800508.
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Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system. The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.
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Rangnekar, Amol S., and William D. Chey. "The FODMAP Diet for Irritable Bowel Syndrome: Food Fad or Roadmap to a New Treatment Paradigm?" Gastroenterology 137, no. 1 (July 2009): 383–86. http://dx.doi.org/10.1053/j.gastro.2009.05.023.
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Lucena Périco, L., and W. MacNaughton. "A62 PROTEASE-ACTIVATED RECEPTOR-2 ACTIVATION ENHANCES EPITHELIAL WOUND HEALING THROUGH SRC PATHWAY-DEPENDENT CELL MIGRATION." Journal of the Canadian Association of Gastroenterology 5, Supplement_1 (February 21, 2022): 71–73. http://dx.doi.org/10.1093/jcag/gwab049.061.
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Abstract Background Protease-activated receptors (PARs) and their activating enzymes play a role in inflammatory bowel disease (IBD) pathogenesis, but the specific roles of PAR2 in disease initiation and progression remain unclear. Interestingly, PAR2 activation has both pro-proliferative and pro-migratory effects and could be involved with restoration of the epithelial barrier following injury. We previously showed that the PAR2 activation increase the epithelial wound healing through ERK, PI3K and JNK pathways. However, the role of Src kinase, which is also activated by PAR2, is not known. Aims We hypothesized that PAR-2 activation induces a wound healing response in intestinal epithelial cells through Src activity. Methods Circular wounds were made in T84 colonic epithelial cells monolayers. Wounded monolayers were treated with the PAR2 activating peptide, 2-furoyl-LIGRLO (2fLI, 5 μM), or the inactive control reverse-sequence peptide, 2-furoyl-OLRGIL (2fO, 5 μM), and live cell imaging was used to record wound closure over a 12 or 24-hr period. The specificity of PAR2 was assessed with a PAR2 inhibitor (GB88). Proliferation and cytotoxicity were measured using EdU and TUNEL assays. The mechanism of action was evaluated using inhibitors of FAK (PF57328 and FAK14) and Src (PP2) and western blot (WB) was used to confirm the protein levels [p-FAK (Y397; Y576/577) and p-Src (Y416)]. For immunofluorescence, images of E-cadherin and F-actin or p-FAK were taken to capture the entire wound border and surrounding cells. Results PAR2 activation by 2fLI promoted wound closure compared to 2fO or vehicle control at the 12 and 24 hr timepoints ( p<0.05). PAR2’s ability to enhance wound closure was blocked with the PAR2 inhibitor, GB88 ( p<0.01). PAR2 activation had no effect on proliferation at the wound-edge and did not cause apoptosis, but enhanced lamellipodia/filopodia formation ( p<0.001), indicating that PAR2 might program the cells toward a migratory phenotype rather than a proliferative phenotype. When we investigated the mechanisms of action, PAR2 activation did not induce focal adhesion kinase (FAK) expression in T84 cells and inhibition of FAK by selective inhibitors (PF573288 and FAK14) did not alter PAR2-induced wound healing. The immunofluorescence for p-FAK (Y397) and WB (Y937 and Y576/577) confirmed these results. However, the Src tyrosine kinase inhibitor (PP2, p<0.0001) inhibited PAR2-induced wound healing. PAR2 activation increased Src phosphorylation (Y416, p<0.05). Conclusions PAR2 activation drives wound healing in part via Src tyrosine kinase activity, but independently of FAK activity. These findings provide a further mechanism whereby PAR2 can participate in the resolution of intestinal wounds in gastrointestinal inflammatory diseases. Funding Agencies CAG, CIHR
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Yang, Lina, Tongtong Guo, Yuanyuan Chen, and Ka Bian. "The Multiple Roles of Periostin in Non-Neoplastic Disease." Cells 12, no. 1 (December 22, 2022): 50. http://dx.doi.org/10.3390/cells12010050.
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Periostin, identified as a matricellular protein and an ECM protein, plays a central role in non-neoplastic diseases. Periostin and its variants have been considered to be normally involved in the progression of most non-neoplastic diseases, including brain injury, ocular diseases, chronic rhinosinusitis, allergic rhinitis, dental diseases, atopic dermatitis, scleroderma, eosinophilic esophagitis, asthma, cardiovascular diseases, lung diseases, liver diseases, chronic kidney diseases, inflammatory bowel disease, and osteoarthrosis. Periostin interacts with protein receptors and transduces signals primarily through the PI3K/Akt and FAK two channels as well as other pathways to elicit tissue remodeling, fibrosis, inflammation, wound healing, repair, angiogenesis, tissue regeneration, bone formation, barrier, and vascular calcification. This review comprehensively integrates the multiple roles of periostin and its variants in non-neoplastic diseases, proposes the utility of periostin as a biological biomarker, and provides potential drug-developing strategies for targeting periostin.
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Kim, Deogil, Dong Woo Lee, Eui Kyun Jeong, Hoo Cheol Lee, Yoon Shin Park, Jue Yeon Lee, Chong Pyung Chung, and Yoon Jeong Park. "NIPEP-IBD; A SYNTHETIC PEPTIDE TARGETING NOVEL MOLECULE, INTEGRIN BETA 1, TO RESTITUTE INTESTINAL EPITHELIAL CELLS FOR INFLAMMATORY BOWEL DISEASE (IBD) TREATMENT." Inflammatory Bowel Diseases 28, Supplement_1 (January 22, 2022): S64. http://dx.doi.org/10.1093/ibd/izac015.103.
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Abstract Under Inflammatory bowel disease (IBD), impaired intestinal barrier from lumen is highly associated with ongoing IBD symptoms and it also contributes as a precursor for IBD. Current IBD therapeutics lack on mucosal regeneration, which the unmet needs could be the next first in class therapeutics for IBD. Here, we propose NIPEP-IBD, a synthetically modified peptide that promotes adhesion, migration, and differentiation of intestinal epithelial cells via interaction of integrin beta 1. From NIBEC’s specialized peptide discovery platform screening, specifically sequenced peptide has been selected for regenerative functional peptide, termed NIPEP-IBD. NIPEP-IBD selectively targeted and bound to integrin beta 1 protein, and its interaction was also verified in vitro, using immunoprecipitation and immunofluorescence assays on epithelial cells. Consequently, NIPEP-IBD increased integrin beta 1 expression, followed by phosphorylated FAK and RhoA proteins. As FAK-RhoA signaling pathway is known to modulate cytoskeletal rearrangement and maturation of epithelial cells, tight junction markers and rapid wound closure of epithelial cells was accelerated by NIPEP-IBD induction. The effect of NIPEP-IBD was further analyzed in vivo IBD model. DSS-induced colitis mouse model was used to analyze therapeutic effect of NIPEP-IBD in each IP and PO administration, and impaired mucosa layer by DSS was recovered by NIPEP-IBD, verified with H&E staining. Moreover, NIPEP-IBD treated mice showed reduced immune cell infiltration in colon tissue and reduced pro-inflammatory cytokines in plasma. In vivo fluorescence imaging system was further used to track distribution of NIPEP-IBD, and NIPEP-IBD specifically binds to impaired epithelium, co-localized with integrin beta 1 protein. The following GLP toxicity studies, ADME studies, and PK studies demonstrated that safety of NIPEP-IBD was verified as a therapeutic agent. Therefore, NIPEP-IBD is a safe and effective therapeutic peptide on IBD patients by restituting epithelial layer of colon and maintain its remission.
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Aftab, Anam, Shaista Habibullah, and Nimra Ilyas Bhutta. "EFFECTS OF FRAGILITY FRACTURE INTEGRATED REHABILITATION MANAGEMENT HIP FRACTURE IN PAKISTANI OLDER ADULTS." Rehabilitation Journal 5, no. 1 (June 30, 2021): 192–97. http://dx.doi.org/10.52567/trj.v5i01.55.
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Objective: to evaluate the effectiveness of fragility Fracture Integrated Rehabilitation Management (FIRM) on older adults of Pakistan after hip fracture surgery. Methodology: A one-group pretest–posttest designwas conducted at the National Institute of Rehabilitation Medicine (NIRM), Islamabad from March 2020 to May 2021.. A n=11 participants with age above 55 years, both male and female, with confirming diagnosed cases of hip fracture were included. Every participats receveied 10 sesssions of Fragility Fracture integrated Rehabilitation Management (FIRM) program in two weeks. Data was collected at baseline at 2nd day and after 10th session on 15th day, through the KOVAL scale to assess the walking ability, the Functional Ambulatory Category (FAC) to assess the level of independence, the modified Barthel index (MBI) for activities of daily living (ADLs), and quality of life (QoL) was assessed by EQ-5D. Data were analyzed by using SPSS Version 21. Result: the mean age 76.45±9.32, of which n=6 (54.6%) were males and n=5(45.4%) were females. after 10th sessions the QoL on EQ-5D, ambulation on FAC and KOVAL scale and the ADL on MBI were significantly improved (p<0.05) with large effect size, except for the anxiety domain of EQ5D and subdomains of MBI; Personal hygiene, feeding, Bowel control, bladder control, Wheelchair, and Chair & bed transfer showed no significant change (p>0.05). Conclusion: FIRM care is found to be effective in improving the walking ability, functional status, ADLs and quality of life in geraiatric population following a hip fracture surgery
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PETCU, Irina Raluca, Daniel SERBAN, Florin DELCEA, Dumitru Cristinel BADIU, Mihaela OPREA (MANDU), Cristina POPESCU, and Gelu ONOSE. "Favorable evolution on functional key components but with multiple remaining phatological elements in a patient diagnosed with toraco-lombar SCI - Case report." Balneo Research Journal, Vol.11, no.4 (December 5, 2020): 549–50. http://dx.doi.org/10.12680/balneo.2020.401.
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Introduction: This paper presents an extremely complex case: paraplegia with T11 neurological level after a thoraco-lumbar spinal cord injury (SCI), with T12 commutative fracture, by falling from about 2 meters (operated on 17.02.2020), currently having an AIS/ Frankel C motor deficit, with multiple complications and successive aggravation, as well as the approach of its therapeutically-rehabilitation management. Materials and methods: 41-year-old male patient admitted to our Clinical Division for motor deficiency of paraplegia type, immediately postoperative AIS/ Frankel C, currently AIS/ Frankel D, for superficial sensitivity disorders with T11 level was clinically and functionally evaluated, according to the implemented standard protocols of our Clinic, by the following measurement evaluation scales: AIS, FIM, QQL (Quality of life), Ashworth, Penn, FAC, WISCI II and investigated paraclinical). Duringh hospitalization, the patient presented numerous aggravations and complications such as: urinary tract infection with E. Coli; left epididymo-orchities, all this aggravating and delaying therapeutic procedures, respectively recovery results. Results: Following an optimal treatment including pharmacological and a complex neuro-rehabilitation program, the patient had a favorable evolution with increased values of the measurement scales (motor AIS with 13 points, FIM motor with 5 points, QQL with 9 points, and FAC with 1 point ); incomplet remission of the bladder and neurogenic bowel dysfunction (intermittent urinary catheterization); increased muscle strength with improved walking speed and balance. Conclusion: The rehabilitation of patients with spinal cord injury is a complex process which requires taking into account all associated pathologies that can play a decisive role in the evolution of the patient. A multidisciplinary team is required for such purposes. Keywords: spine-cord injury, paraplegia, poly-pathologic, rehabilitation,
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Mao, Q., W. Liang, Y. Zhang, G. Brat, J. Grahammer, J. Christensen, D. Cooney, et al. "Two-Photon Microscopy Reveals Changes in Cellular Morphology and NADH and FAD Oxidation-Reduction States in Ischemic Small Bowel Allografts." Transplantation Journal 94, no. 10S (November 2012): 294. http://dx.doi.org/10.1097/00007890-201211271-00547.
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Mao, Q., W. Liang, Y. Zhang, G. Brat, J. Grahammer, J. Christensen, D. Cooney, et al. "Two-Photon Microscopy Reveals Changes in Cellular Morphology and NADH and FAD Oxidation-Reduction States in Ischemic Small Bowel Allografts." Transplantation Journal 94, no. 10S (November 2012): 741. http://dx.doi.org/10.1097/00007890-201211271-01452.
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Teixeira, Jorge, Mário Ribeiro, and Nélson Pinho. "Advanced warpage characterization for FOWLP." International Symposium on Microelectronics 2013, no. 1 (January 1, 2013): 000641–46. http://dx.doi.org/10.4071/isom-2013-wp21.
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Current standards for silicon wafers shape characterization use simple metrics. Warpage and bow are computed as the mean surface wafer height range or the mean surface wafer center height, respectively [1]. These metrics are valid for silicon wafers because of their homogenous and linear thermomechanical properties [2]. In fan-out wafer level package (FO-WLP), embedded Wafer Level Ball Grid Array in specific (eWLB), the use of epoxy mold compound that works both as the physical carrier of the dies and as the base of second level connections has a major impact on the overall macroscopic behavior of the wafer, inducing shapes that do not follow a simple bended or bowed wafer, impacting wafer processability [3]. Warped wafers can affect device performance, reliability, and linewidth control in various processing steps [3]. Early detection will minimize cost and processing time. In our research, we present a solution for wafer characterization in FO-WLP by increasing the information vector that one obtains from standard automated non-contact scanning equipment. For this, we defined wafer shape and wafer ratio as the two new metrics besides warpage, creating a three dimensional vector that can be used to compare and evaluate wafers in high volume production or even single wafer analysis. This is a major improvement over previously used approaches, in which only the average warpage is considered. These metrics were determined by the developed numeric algorithm and their validity was demonstrated through the use of different production conditions, wafer constructions and production monitoring. The proposed approach requires no extra processing steps and time, as compared to conventional off-line methods. Experimental results demonstrate its feasibility and repeatability. This methodology was successfully used in the field and proved to be of high value when evaluating wafer geometrical requirements for both product development and process monitoring.
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Cohavy, O., D. Bruckner, L. K. Gordon, R. Misra, B. Wei, M. E. Eggena, S. R. Targan, and J. Braun. "Colonic Bacteria Express an Ulcerative Colitis pANCA-Related Protein Epitope." Infection and Immunity 68, no. 3 (March 1, 2000): 1542–48. http://dx.doi.org/10.1128/iai.68.3.1542-1548.2000.
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ABSTRACT Bacteria are a suspected pathogenic factor in inflammatory bowel disease, but the identity of the relevant microbial species remains unresolved. The pANCA autoantibody is associated with most cases of ulcerative colitis (UC) and hence reflects an immune response associated with the disease process. This study addresses the hypothesis that pANCA identifies an antigen(s) expressed by bacteria resident in the human colonic mucosa. Libraries of colonic bacteria were generated using aerobic and anaerobic microbiologic culture conditions, and bacterial pools and clonal isolates were evaluated for cross-reactive antigens by immunoblot analysis using the pANCA monoclonal antibody Fab 5-3. Two major species of proteins immunoreactive to pANCA monoclonal antibodies were detected in bacteria from the anaerobic libraries. Colony isolates of the expressing bacteria were identified as Bacteroides caccae andEscherichia coli. Isolation and partial sequencing of theB. caccae antigen identified a 100-kDa protein without database homologous sequences. The E. coli protein was biochemically and genetically identified as the outer membrane porin OmpC. Enzyme-linked immunosorbent assay with human sera demonstrated elevated immunoglobulin G anti-OmpC in UC patients compared to healthy controls. These findings demonstrate that a pANCA monoclonal antibody detects a recurrent protein epitope expressed by colonic bacteria and implicates colonic bacterial proteins as a target of the disease-associated immune response.
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Steenholdt, C., Y. Palarasah, K. Bendtzen, A. Teisner, J. Brynskov, B. Teisner, and C. H. Nielsen. "Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease." Alimentary Pharmacology & Therapeutics 37, no. 12 (May 7, 2013): 1172–83. http://dx.doi.org/10.1111/apt.12330.
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Fujiyama, Y., K. Kobayashi, S. Senda, Y. Benno, T. Bamba, and S. Hosoda. "A novel IgA protease from Clostridium sp. capable of cleaving IgA1 and IgA2 A2m(1) but not IgA2 A2m(2) allotype paraproteins." Journal of Immunology 134, no. 1 (January 1, 1985): 573–76. http://dx.doi.org/10.4049/jimmunol.134.1.573.
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Abstract Three bacterial strains of Bifidobacterium and Clostridium sp. from patients with inflammatory bowel disease (I.B.D.) and Streptococcus pneumoniae from a patient with pneumonia were identified to produce extracellular proteases cleaving IgA into Fab and Fc fragments. Although the proteases from the Bifidobacterium and the Streptococcus pneumoniae showed the characteristics of typical IgA1 proteases, cleaving the IgA of only the IgA1 subclass, the protease from Clostridium sp. revealed a dual substrate specificity, in that it cleaved both IgA1 and IgA2 of the A2m(1) allotype. The latter protease, however, did not show any activity with respect to the IgA2 of the A2m(2) allotype. Fc fragments isolated from the IgA1 and the IgA2 A2m(1) by digestion with the Clostridium sp. protease were identified to have an identical amino terminal residue of valine. The site of cleavage in both the alpha 1 and the alpha 2 of A2m(1) by the protease was assumed to be an identical peptide bond at Pro(221)-Val(222), which is a common one present just before the hinge of both the alpha 1 and the alpha 2 of the A2m(1) but not of the alpha 2 of the A2m(2). The protease was sensitive to ethylene-diamino tetraacetic acid, a chelating agent, similar to other already reported IgA1 proteases.
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Banaag, Mareshah Jaira M., Evelyn E. Daulat, L. Mediodia, S. Fernandes, Asad I. Dajani, A. M. Abuhammour, and Mazin R. Aljabiri. "Mo1338 Is Focal Active Colitis a New Miscellany of Inflammatory Bowel Disease? And Is There a Role for 5 ASA in the Management of FAC?" Gastroenterology 144, no. 5 (May 2013): S—640. http://dx.doi.org/10.1016/s0016-5085(13)62371-9.
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Regev, S., G. Goren, D. Schwartz, R. Sergienko, M. Friger, A. Nemirovsky, D. Greenberg, et al. "P543 The role of social support on psychological distress and health-related quality of life in adults with mild to moderately active Crohn’s disease." Journal of Crohn's and Colitis 15, Supplement_1 (May 1, 2021): S513—S514. http://dx.doi.org/10.1093/ecco-jcc/jjab076.664.
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Abstract Background Medical and psychological factors contribute to the heightened psychological distress and reduced health-related quality of life in patients with Crohn’s disease. Whether Social Support plays a role in this scenario is unknown. We used the Multidimensional Scale of Perceived Social Support (MSPSS) to investigate whether Social Support associates with psychological distress and quality of life in Crohn’s disease. Methods Consecutive adult patients with Crohn’s disease, presenting at specialist gastroenterology services or recruited by advertising, with mild to moderate disease activity by the Harvey-Bradshaw Index (HBI), were enrolled into the study. Patients completed the 12-item MSPSS questionnaire that measures psychological support in three categories: Family, Friends and Significant Other, and provides individual category scores and a total score (range of all scores 1–7; a higher score indicates more social support). Patients also completed the following questionnaires: psychological distress (Brief Symptom Inventory, with Global Severity Index, GSI), quality of life (Short Inflammatory Bowel Disease Questionnaire, SIBDQ), satisfaction with life (SWLS), family stress (Family Assessment Device, FAD), coping strategies (Brief-COPE), and presenteeism and work activity (WPAI). Statistics: Spearman rho. *p<0.05, **p<0.01. Results The cohort comprised 126 patients, mean (SD) age 33.7 (10.6) years, females 79%, HBI 8.4 (2.5), CRP 1.2 (2.3), calprotectin 394 (674). MSPSS scores were as follows: Total score 5.72 (1.14), Friends 5.36 (1.34), Family 5.73 (1.14), and Significant Other 6.07 (1.15); Cronbach’s α ≥ .877. MSPSS scores correlated negatively with family stress measure FAD: Friends -.258**, Family -.732**, Significant Other -.401**; and with GSI psychological stress measure: Friends -305**, Family -.352**, Significant Other -.245**. MSPSS correlated positively with SIBDQ quality of life: Friends .300**, Family .188*, Significant Other .200*; and with satisfaction with life SWLS: Friends .379**, Family .333**, Significant Other .245**. MSPSS correlations with emotion-focused coping were: Friends -.337**, Family -.263**, Significant Other -.329**. MSPSS Family score correlated negatively with WPAI presenteeism -.270*, and WPAI work activity -.294**. Conclusion In mild to moderate Crohn’s disease, strong social support was associated with better quality of life, more satisfaction with life, and better performance in the work arena. Social support was associated with reduced psychological distress, reduced family stress, and less use of emotion-focused coping. This research shows the importance of social support in improving the psychological condition of patients with Crohn’s disease.
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SAGLAM, Ali-Osman, REBEDEA Ana Carmen, George PATRAŞCU, Luminita NIRLU, Mustafa Turgut YILDIZGOREN, Cristina POPESCU, and Gelu ONOSE. "Very complex and difficult rehabilitation process in a post traumatic SCI (Spinal Cord Injury) complete tetraplegic patient with intense and refractory spasticity and frequency of spasm with presacral pressure sores (successfully operated)- case report." Balneo Research Journal, Vol.11, no.4 (December 5, 2020): 554–55. http://dx.doi.org/10.12680/balneo.2020.403.
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Introduction. Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion.(1) As a result of the injury, the functions performed by the spinal cord are interrupted at the distal level of the injury. SCI causes serious disability among patients.(2) The treatment and rehabilitation period is long, expensive and exhausting in SCI. The results of SCI bring not only damage to independence and physical function, but also include many complications from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity, autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive disorders are frequent complications after SCI.(3) Material and method. Having the patient’s consent and The Teaching Emergency Hospital “Bagdasar-Arseni” Ethics Committee’s approval, a 48 years old patient, complete tetraplegic with intense and refractory spasticity and frequency of spasm with presacral pressure sores (successfully operated) post traumatic spinal cord injury. The patient was functionally assessed using the following scales: : Glasgow Outcome Scale Extended, Modified Rankin Scale, Modified Ashworth, Penn Spasm Frequency Scale Functional Independence Measure, FAC International Scale, Quality of Life Assessment. Conclusions. Spasticity is a common secondary impairment after SCI characterized by hypertonus, increased intermittent or sustained involuntary somatic reflexes (hyperreflexia), clonus and painful muscle spasms. Severe spasticity may contribute to increased functional impairment, contractures, ulcers, posture disorders and pain. Treatment should start as soon as possible to prevent such negative effects. Keywords: tetraplegia, spinal cord injury, spasticity, pressure sores, traumatism, rehabilitation,
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Picot, Denis, Sabrina Layec, Eloi Seynhaeve, Laurence Dussaulx, Florence Trivin, and Marie Carsin-Mahe. "Chyme Reinfusion in Intestinal Failure Related to Temporary Double Enterostomies and Enteroatmospheric Fistulas." Nutrients 12, no. 5 (May 11, 2020): 1376. http://dx.doi.org/10.3390/nu12051376.
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Some temporary double enterostomies (DES) or entero-atmospheric fistulas (EAF) have high output and are responsible for Type 2 intestinal failure. Intravenous supplementations (IVS) for parenteral nutrition and hydration compensate for intestinal losses. Chyme reinfusion (CR) artificially restores continuity pending surgical closure. CR treats intestinal failure and is recommended by European Society for Clinical Nutrition and Metabolism (ESPEN) and American Society for Parenteral and Enteral Nutrition (ASPEN) when possible. The objective of this study was to show changes in nutritional status, intestinal function, liver tests, IVS needs during CR, and the feasibility of continuing it at home. A retrospective study of 306 admitted patients treated with CR from 2000 to 2018 was conducted. CR was permanent such that a peristaltic pump sucked the upstream chyme and reinfused it immediately in a tube inserted into the downstream intestine. Weight, plasma albumin, daily volumes of intestinal and fecal losses, intestinal nitrogen, and lipid absorption coefficients, plasma citrulline, liver tests, and calculated indices were compared before and during CR in patients who had both measurements. The patients included 185 males and 121 females and were 63 ± 15 years old. There were 37 (12%), 269 (88%) patients with EAF and DES, respectively. The proximal small bowel length from the duodeno-jejunal angle was 108 ± 67 cm (n = 232), and the length of distal small intestine was 117 ± 72 cm (n = 253). The median CR start was 5 d (quartile 25–75%, 2–10) after admission and continued for 64 d (45–95), including 81 patients at home for 47 d (28–74). Oral feeding was exclusive 171(56%), with enteral supplement 122 (42%), or with IVS 23 (7%). Before CR, 211 (69%) patients had IVS for nutrition (77%) or for hydration (23%). IVS were stopped in 188 (89%) 2 d (0–7) after the beginning of CR and continued in 23 (11%) with lower volumes. Nutritional status improved with respect to weight gain (+3.5 ± 8.4%) and albumin (+5.4 ± 5.8 g/L). Intestinal failure was cured in the majority of cases as evidenced by the decrease in intestinal losses by 2096 ± 959 mL/d, the increase in absorption of nitrogen 32 ± 20%, of lipids 43 ± 30%, and the improvement of citrulline 13.1 ± 8.1 µmol/L. The citrulline increase was correlated with the length of the distal intestine. The number of patients with at least one liver test >2N decreased from 84–40%. In cases of Type 2 intestinal failure related to DES or FAE with an accessible and functional distal small bowel segment, CR restored intestinal functions, reduced the need of IVS by 89% and helped improve nutritional status and liver tests. There were no vital complications or infectious diarrhea described to date. CR can become the first-line treatment for intestinal failure related to double enterostomy and high output fistulas.
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Afify, Zeinab, Manuela Orjuela, Christine Moore Smith, Mansi Dalal, James B. Ford, Pallavi Pillai, Joanna Robles, et al. "Outcome of Post Solid Organ Transplant Burkitt Lymphoma (PSOT-BL): A Report from the Pediatric PTLD Collaborative (PPC)." Blood 138, Supplement 1 (November 5, 2021): 2498. http://dx.doi.org/10.1182/blood-2021-149033.
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Abstract Background Post solid organ transplant Burkitt lymphoma (PSOT-BL) is a rare form of monomorphic post-transplant lymphoproliferative disease (M-PTLD). Outcome data in pediatric patients are limited and guidelines on optimal treatment in PSOT-BL are lacking. Methods Retrospective study and analysis of clinical characteristics, treatment, and outcome data from patients diagnosed with PSOT-BL at age ≤ 21 years (y) in 11 US pediatric transplant centers. Results We identified 28 patients transplanted between 1993-2016 who developed PSOT-BL. Median age at organ transplantation and at diagnosis of PSOT-BL was 2.9y (range, 0.1-14) and 7.5y (range, 7-17), respectively, with median interval from transplant to PSOT-BL diagnosis of 3.8y (range 2-7). Heart and liver were the most frequently transplanted organs (n=14, 11), while bowel, kidney, and lung were each transplanted in one patient. Immunosuppressive therapy at the time of PSOT-BL diagnosis was tacrolimus alone (n=9), or in combination with mycophenolate (n=7), azathioprine (n=6), cyclosporin (n=3), or prednisone (n=3). None were receiving an mTOR inhibitor at time of PSOT-BL diagnosis. Six, twelve, and ten patients corresponded to Murphy stages II, III, and IV, respectively. Lactate dehydrogenase was elevated in 23 patients (82%) and was > 2x upper limit of normal in 14 (50%). All tumors were pathologically consistent with BL; MYC FISH testing was positive in 10/10 tumors tested, while 21/23 tumors (90%) had detectable Epstein Barr Virus. Rituximab-containing regimens were given to 25/28 patients (93%). These treatment regimens were as follows: rituximab alone (n=2), low dose cyclophosphamide, prednisone, and rituximab (CPR) (n=10), Burkitt lymphoma specific therapy: (FAB/LMB chemotherapy (n=3) or FAB/LMB therapy with rituximab (n=8)), reduced dose FAB/LMB (n=2), diffuse large B-cell lymphoma (DLBCL) regimens including EPOCH-R (n=2) and R-CHOP (n=1). Treatment modifications/reductions were infrequent. Methotrexate dose modification and/or omission were required in four patients due to renal dysfunction (n=3) and ascites (n=1). Doxorubicin was electively eliminated in one cardiac transplant recipient due to concern for cardiotoxicity and dose-reduced in another due to prolonged myelosuppression. There was no treatment related mortality. There were two episodes of rejection, one was a liver rejection that was successfully treated without graft loss, the other occurred after achieving partial response (PR) to 3 cycles of CPR, required intensive immune suppression, and was followed by PTLD/DLBCL and death from PTLD progression. There were two additional cases of a second PTLD/DLBCL. One died of PTLD progression nine months after developing a second PTLD and the other is alive in complete remission (CR) 17 months after diagnosis of a second PTLD. Of the two patients treated with rituximab alone, one had no response and the other relapsed. Both were subsequently treated with BL chemotherapy and are alive in CR 15- and 7-years following BL diagnosis, respectively. For all study patients over a median of 6.8y follow-up (range, 0.5-17), 3-year event-free survival (EFS) was 73.5% and 3-year overall survival (OS) was 92.6%, see figure. Three patients died of Burkitt lymphoma (all had been treated with CPR, experienced treatment failure and required treatment escalation to intensive BL chemoimmunotherapy but died of progressive disease). Of the 11 patients who received Burkitt lymphoma intensive therapy, all are alive in CR. One had progressed on treatment but achieved CR with further treatment intensification. Another developed a second PTLD/DLBCL, with subsequent CR. Conclusion This collaborative study represents the largest pediatric series of PSOT-BL reported to date. In this study patients with PSOT-BL treated with intensive BL directed therapy appear to have comparable outcome to immunocompetent pediatric patients with BL. Figure 1 Figure 1. Disclosures Orjuela: ATARA Pharmaceuticals: Other: Scientific Advisory Board.
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Bilski, Jan, Agnieszka Mazur-Bialy, Dagmara Wojcik, Marcin Magierowski, Marcin Surmiak, Slawomir Kwiecien, Katarzyna Magierowska, Magdalena Hubalewska-Mazgaj, Zbigniew Sliwowski, and Tomasz Brzozowski. "Effect of Forced Physical Activity on the Severity of Experimental Colitis in Normal Weight and Obese Mice. Involvement of Oxidative Stress and Proinflammatory Biomarkers." Nutrients 11, no. 5 (May 21, 2019): 1127. http://dx.doi.org/10.3390/nu11051127.
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Inflammatory bowel diseases are a heterogeneous group of disorders represented by two major phenotypic forms, Crohn’s disease and ulcerative colitis. Cross talk between adipokines and myokines, as well as changes in intestinal microcirculation, was proposed in pathogenesis of these disorders. C57BL/6 male mice were fed ad libitum for 12 weeks a standard (SD) or high-fat diet (HFD). After the adaptation period, two groups of animals fed SD or HFD were subjected to 6 weeks of the forced treadmill exercise and the experimental colitis was induced in both groups of sedentary and exercising mice fed SD and HFD by intra-colonic administration of 2,4,6-trinitrobenzenesulfonic acid. The disease activity index (DAI), colonic blood flow (CBF), the weight of animals, caloric intake, the mesenteric fad pad, the colonic oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity and intestinal expression and protein content of proinflammatory markers were evaluated. Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF and exacerbated in those fed a HFD. The contents of MDA, GSH, and SOD activity were significantly increased in both SD and HFD fed mice with treadmill exercise as compared with sedentary mice. In sedentary HFD mice a significant increase in the intestinal oxidative stress parameters and mucosal expression of IL-1β, TNF-α, IL-17, IFNγ, IL-6, and IL-10 protein were observed and these effects were aggravated in mice subjected to forced treadmill exercise. The mucosal expression of mRNA for TNF-α, IL-1β, iNOS, COX-2, SOD-1, SOD-2, GPx mRNAs, and the hypoxia inducible factor (HIF)-1α protein expression were upregulated in colonic mucosa of treadmill exercising HFD mice with colitis compared with those without exercise. We conclude that forced treadmill running exacerbates the severity of colonic damage in obese mice due to a fall in colonic microcirculation, an increase in oxidative stress, and the rise in expression and activity of proinflammatory biomarkers.
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Ozen, Mehmet, Onur Keskin, Orhan Kucuksahin, Ufuk Ilgen, Pervin Topcuoglu, Murat Turgay, Murat Toruner, and Gunhan Gurman. "Tumor necrosis factor inhibitors and acute leukemia in two cases." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e18010-e18010. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e18010.
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e18010 Background: Inhibitors of tumor necrosis factor alpha (anti-TNF agents) are commonly used in Crohn’s disease and rheumatoid arthritis. Relationship between TNF inhibitors and development of malignancy, e.g., lymphoma and solid tumors, is defined recently. However, a few authors reported leukemia. Crohn’s disease and also azothioprine may also be associated with leukemia. Here, we are presenting two acute myeloid leukemia (AML) cases using azothioprine and anti-TNF inhibitors for Crohn’s disease. Methods: Observational case report. Results: Case 1: A 56-year-old male patient with active Crohn’s disease for 4 years was refractory to first line mesalazine, corticosteroid and azothioprine treatment. So, anti-TNF monoclonal antibody (moAb) (Adalimumab) had been given. After second dose of adalimumab treatment AML (AML-M2 as FAB) developed. Case 2: A 38-year-old male had been diagnosed with ankylosing spondylitis for 7 years and Crohn’s disease for 2 years. He had been treated with salazopyrin and indomethacin. Anti-TNF etanercept (50 mg/wk) was started 30 months ago due to severe active pulmonary disease. After 1 year, he developed active Crohn’s disease. So, the treatment changed to infliximab. Also, mesalazine and azothioprine were added to treatment. On the 18th month of the infliximab t(15;17) positive acute promyelocytic leukemia were developed in the patient. Conclusions: Blocking TNF with anti TNF agents may cause blocking apoptosis and inhibit natural killer activity. So, antitumoral activity of natural killer cells is blocked by these agents. TNF alpha gene mutation has been associated with CLL, lymphoma, myelodysplastic syndrome and secondary AML. Azothioprine may also increase leukemia, lymphoma and solid tumors risk at patient on anti TNF treatment. Following the diagnosis of Crohn’s disease without immunomodulator treatment a case had developed acute leukemia in the literature. In our patients, anti-TNF, azothioprine and inflammatory bowel disease may be cause acute leukemia cumulatively. Physicians should be careful and regularly check the patients using anti-TNF agents in considering of malignancy development. In conclusion, the pathogenesis of leukemia development after TNF blockage should be clarified.
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Furrer, G., A. Stapfer, and U. Glaser. "Zur nacheiszeitlichen Gletschergeschichte des Liefdefjords (Spitzbergen) (Ergebnisse der Geowissenschaftlichen Spitzbergenexpedition 1990)." Geographica Helvetica 46, no. 4 (December 31, 1991): 147–55. http://dx.doi.org/10.5194/gh-46-147-1991.
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Abstract. Der Liefdefjord in Nordwestspitzbergen (79 &frac12°N)war 1990 – und 1991 nochmals – das Arbeitsgebiet der internationalen, interdisziplinären Spitzbergenexpedition SPE '90. Schwerpunkte der Forschungsarbeiten sind nacheiszeitliche und aktuelle geomorphologische und geoökologische Prozesse in diesem vom Menschen noch fast völlig unberührten Raum. Das Expeditionsgebiet besitzt zahlreiche Kar- und einzelne Talgletscher sowie ein stark differenziertes, «alpin» anmutendes Relief. Mit unserem Teilprojekt «Gletscherentwicklung und Moränendatierung» wird versucht, einen Beitrag zur noch wenig bekannten Gletschergeschichte Spitzbergenszuleisten: – Viele Gletscher – so der Monacobreen – münden heute direkt ins Meer oder enden nahe der Küste. Die Gletschervorfelder sind in der Regel durch einen markanten Wallmoränenkomplex (Moränenwall) umschlossen. Das Moränenmaterial im gletschernahen Bereich wurde von Vorstößen der Neuzeit (ab 16. Jahrhundert) abgelagert. – Im Liefdefjorden und Bockfjorden konnten aber durch Grabungen an der Außenseite der Moränenwälle mehrere, von Gletschern überfahrene, fossileorganische Bodenhorizonte (fAh) gefunden werden. Deren Radiokarbondatierungen lassen auf Gletschervorstöße im frühen und späten Älteren Subatlantikum (2800 – 1000 yBP) und im frühen und mittleren Jüngeren Subatlantikum (ab 1000 yBP) schließen. – Mächtigkeit und Polleninhalt der datierten fossilen Boden- und Torfbildungen deuten daraufhin, daß die Vegetation zur Zeit der organischen Sedimentation ähnlich wie heute in Küstennähe entwickelt war. Die klimatischen Bedingungen dürften während der früheren Torf-/Bodenbildungsphasen zumindest nicht ungünstiger gewesen sein als heute. Diese Resultate führen zur Schlußfolgerung, daß die heutigen Gletschervorfelder von Moränenwällen umschlossen sind, die aus Material von verschiedenen Gletschervorstößen zusammengesetzt sind, und daß die maximale Ausdehnung der Gletscherhochstände in den letzten 2800 Jahren (vermutlich im ganzen Holozän) stets etwa dieselbe war. Diese Charakteristika treffen auch für die nacheiszeitliche Gletschergeschichte der Alpen zu. – Im Untersuchungsgebiet konnten keine Hinweise auf ältere postglaziale und spätglaziale Gletschervorstöße gefunden werden. Vorallem die Frage nach dem Gletscherverhalten während der Jüngeren Dryas (11000–10200 yBP) bleibt offen. Aufgrund unserer Beobachtungen muß man vermuten, daß allfällige Gletschervorstöße während dieser Zeit die Maximalstände des Subatlantikums nicht übertroffen haben. –Spätestens zu Beginn des Alleröds (11800–11000 yBP) war der Liefdefjord mindestens soweit eisfrei wie heute.
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Winthrop, K., F. A. Farraye, K. M. Sullivan, D. O. Willer, P. Vink, and F. Tavares-Da-Silva. "AB1072 HERPES ZOSTER IN INDIVIDUALS WITH AUTOIMMUNE DISEASES AND RECOMBINANT HERPES ZOSTER VACCINE AS A PREVENTATIVE STRATEGY." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1655.2–1656. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1806.
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BackgroundIndividuals with autoimmune diseases (AIDs) are particularly vulnerable to herpes zoster (HZ) and its related complications. Although the live attenuated HZ vaccine is contraindicated in many of these individuals, the two-dose non-live recombinant zoster vaccine (RZV) can be used in immunosuppressed individuals. Based on accumulating data from RZV studies within specific immunosuppressive conditions, recently updated guidelines recommend RZV not only in immunocompetent adults aged ≥50 years, but also in adults aged ≥18 years (EU)/≥19 years (USA) at risk of HZ due to immunodeficiency or immunosuppression.1–3ObjectivesTo evaluate the burden of HZ in individuals with AIDs and the use of RZV as a preventative strategy.MethodsWe reviewed PubMed for available data on HZ incidence, summarised RZV data (effectiveness and safety) and the current recommendations for RZV in individuals with AIDs. The latest search was conducted in September 2021.ResultsHZ incidence in the general population is 4–7/1000 person-years (increases with age) and 8–15/1000 person-years in individuals with AIDs. Common immunosuppressive and immunomodulatory therapies can predispose individuals to HZ, as shown by large meta-analyses of interventional and observational studies. No published randomised controlled trial data of RZV in AID populations were found in our search. In two retrospective cohort studies in patients with inflammatory bowel disease (IBD), 4,5 RZV demonstrated high vaccine effectiveness (OR 0.64; 95% CI 0.44, 0.77).4 In a real-world observational study investigating RZV in beneficiaries of the Medicare national health insurance program in the USA, individuals with AIDs achieved vaccine effectiveness of 68.0% (95% CI 62.3%, 72.8%), which was similar to the overall population (70.1% [95% CI 68.6%, 71.5%]).6 In two single-centre, retrospective studies of RZV in individuals with AIDs, including rheumatoid arthritis (RA), adverse events after the first RZV dose were mild7,8. Disease flares were uncommon, mild and self-limiting, although a flare at the first RZV dose was significantly associated with an increased risk of a flare at the second dose (hazard ratio 3.9; P=0.0015)7. In addition, glucocorticoid use during vaccination was significantly associated with flares (odds ratio [OR] 2.31; P=0.004; Lenfant, 2021)7. In a study of individuals with IBD, receiving ≥1 RZV dose was associated with a low flare rate9. Current RZV guidelines vary by country and will be revised as new data emerge. Ongoing studies include phase 4 studies of individuals with RA and IBD receiving immunotherapies, and a study investigating the immunogenicity and safety of RZV in individuals with stable systemic lupus erythematosus.ConclusionIndividuals with AIDs are at increased risk of HZ and its related complications, which may be due to either or both of their underlying condition and the treatment(s) they are receiving. The developing collective scientific evidence from the published literature on RZV in individuals with AIDs demonstrates a favourable benefit:risk profile for RZV in this population which contributed to the recent USA ACIP recommendation. Further studies are warranted to evaluate potential effects of individual conditions and immunotherapies on vaccine efficacy and methods to optimise vaccine use.References[1]Dooling KL, et al. MMWR Morb Mortal Wkly Rep, 2018[2]GlaxoSmithKline, Press Release, 2021[3]GlaxoSmithKline, RZV EU SmPC, 2021[4]Kochhar GS, et al. Vaccine, 2021[5]Khan N, et al. Clin Gastroenterol Hepatol, 2021[6]Izurieta HS, et al. Clin Infect Dis, 2021[7]Lenfant T, et al. Rheumatology, 2021[8]Stevens E, et al. ACR Open Rheumatol, 2020[9]Satyam VR, et al. Dig Dis Sci, 2020AcknowledgementsThis abstract was funded by GlaxoSmithKline Biologicals SA. Medical writing support in the preparation of this abstract was provided by Silvia Pregnolato of OPEN Health Communications, London, UK, with financial support from GlaxoSmithKline Biologicals SA.Disclosure of InterestsKevin Winthrop Consultant of: KLW has received consultancy fees from GlaxoSmithKline, Bristol Myers Squibb, Pfizer, AbbVie, Union Chimique Belge, Eli Lilly, Galapagos, Roche, Gilead, Sanofi, Regeneron, AstraZeneca and Novartis., Grant/research support from: KLW has received research grants from Bristol Myers Squibb and Pfizer., Francis A Farraye Consultant of: KMS has received consultancy fees from and been part of publication committees for GlaxoSmithKline., Keith M Sullivan Shareholder of: FAF is a stockholder in Innovation Pharmaceuticals., Paid instructor for: FAF sits on the data safety monitoring board for Eli Lilly and Theravance., Consultant of: FAF has received consultancy fees from Arena, Bristol Myers Squibb, Braintree Labs, GI reviewers, GlaxoSmithKline, Iterative Scopes, Janssen, Pfizer and Sebela., David O Willer Shareholder of: DOW holds restricted share stock ownership for GlaxoSmithKline., Employee of: DOW is employed by GlaxoSmithKline., Peter Vink Employee of: PV was an employee at GSK at the time this work was completed., Fernanda Tavares-Da-Silva Shareholder of: FTDS holds restricted share stock ownership for GlaxoSmithKline., Employee of: FTDS is employed by GlaxoSmithKline.
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Daia, Cristina, Alexandra Cocolos, Andrei Ohriniuc, Bogdan Marinescu, Elena Bruma, Elena Constantin, Aura Spinu, Ioana Andone, Cristina Popescu, and Gelu Onose. "Successful rehabilitation program after AIS/Frankel C paraplegia through a recently operated lumbar disc hernia." Balneo and PRM Research Journal, Vol.13, no.1 (March 19, 2022): 489. http://dx.doi.org/10.12680/balneo.2022.489.
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Intervertebral disc herniation is the pathological process by which fragments of the nucleus pul-posus tear the fibers of the annulus fibrosus and come into contact with the root of the spinal nerve (1). The most significant functional damage generated by the lumbar disc herniation is paraplegia and can be ameliorated by an early and staged specific rehabilitation program. Materials and Methods: This paper presents the case of a 56-year-old patient who was admitted to the Neurosurgery Clinic (NCH) III of SCUBA for low back pain and motor deficit, AIS Frankel C paraplegia. The left lower limb was more affected than the right one. It occurred following a thoraco-lumbar medullary compression and a paramedian lumbar disc herniation L3. The pa-tient was treated surgically. Subsequently, the patient was transferred to the Neuro-Muscular Recovery Clinic of SCUBA for the specific rehabilitation treatment, with indication for mobiliza-tion. He was dynamically evaluated using the following scales: quality of life assessment (QOL), modified Ashworth scale, Functional Assessment Classification, FAC, Activities of daily living (ADL), Spinal Cord Independence Measure (SCIM), evaluation of muscle strength on Medical Re-search Council, MRC, scale, evaluation of American Spinal Injury Association Impairment Scale (AIS). Results: The patient benefited from a complex program of neuro-muscular rehabilitation, hav-ing a favorable evolution with an improving score of the evaluating scales and finally gaining his gait balance, including ascending and descending stairs (instrumentally assisted for left plan-tar dorsiflexion movement with orthosis walking). At discharge the patient’s neurological defi-cit was reclassified as AIS D paraplegia, with the neurogenic bladder and bowel having been remitted. Discussions: The disc herniation at L3 level generated a cauda equina syndrome, which initially generated a paraplegia. When the inflammation remitted it became clear that the left L4 root was affected, with a complete deficit of plantar dorsiflexion. In conclusion it was not a case of spinal cord syndrome (as the spinal cord ends at L2 level) or conus medullaris syndrome. Conclusions: The interdisciplinary therapeutic approach together with a specific, customized re-habilitation program for a patient with AIS C paraplegia after a surgically treated disc hernia is successfully improving the neuromuscular deficit and upgrading the patient's quality of life. Keywords: rehabilitation, disc hernia, low back pain, paraplegia
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Ramanarayanan, Jeyanthi, Alan N. Baer, Minoo Battiwalla, Laurie A. Ford, Meir Wetzler, and Maria R. Baer. "Autoimmune Disease (AD) in Patients with Myelodysplastic Syndrome (MDS): A Retrospective Single Institution Study." Blood 104, no. 11 (November 16, 2004): 4736. http://dx.doi.org/10.1182/blood.v104.11.4736.4736.
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Abstract Autoimmune disease (AD) can manifest uncommonly either at the time of diagnosis of MDS or during its course. When present, AD generally responds to immunosuppressive therapies, but cytopenias and immunosuppression associated with MDS compromise delivery of these therapies. Few studies have investigated the impact of co-existing AD on the course and outcome of patients with MDS. Our objective was to evaluate the clinical manifestations, laboratory characteristics, response to therapy and survival of MDS patients with AD. Records of patients evaluated at Roswell Park Cancer Institute with pathologically demonstrated MDS between 1993 and 2003 (n=277) were reviewed and patients with evidence of AD were identified. Patients with laboratory abnormalities without disease manifestations were excluded, as were patients with therapy-related MDS following treatment for AD. 13 patients (4%) were identified with co-existing MDS and AD. The initial presentation was AD in 6 (46%) and MDS in 4 (31%), while 3 patients (23%) had near-simultaneous diagnoses of both conditions. The spectrum of AD in these patients included systemic vasculitis in 3 patients, systemic lupus erythematosus in two and rheumatoid arthritis, temporal arteritis, cryoglobulinemia, aphthous stomatitis, pyoderma gangrenosum, inflammatory bowel disease, erythema nodosum and Evans syndrome in one patient each. Anti-double stranded DNA (levels ≥ 40.0 u/ml; normal range 0.0–3.5u/ml), ANA (≥1:160), cold agglutinins, low C3 and elevated ESR (≥100mm/hr) were the serological abnormalities detected at the time of AD diagnosis. Eleven of 13 patients were female, and median age at diagnosis of MDS was 65 years, while the entire cohort was 44% female (p=0.005) and had a median age of 71 yrs at diagnosis. FAB subtypes were RA (n=7), RAEB (n=3), CMMoL (n=2) and RARS (n=1). Cytogenetics were normal in 5 patients; abnormalities in the other 8 patients included −7, +8, and del(5q). The median survival of patients from diagnosis of MDS was 48 months and the survival from diagnosis of AD was 46 months. Known causes of death in 6 patients included sepsis, intracranial hemorrhage, lung cancer and transplant-associated multiorgan failure. Based on this study, AD occurs in 4% of MDS patients, predominantly affects female patients, and has heterogeneous clinical manifestations.The pathobiologic implication of the occurrence of AD at the same time or after the diagnosis of MDS is that the dysplastic clone might be responsible for the induction of immune dysregulation.
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Colovic, Natasa, Zoran Rajic, Mirjana Sretenovic, Mirjana Stojkovic, and Milica Colovic. "Neutropenic enterocolitis in acute myeloid leukemia." Acta chirurgica Iugoslavica 51, no. 2 (2004): 127–31. http://dx.doi.org/10.2298/aci0402127c.
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In this report we focus on the importance of an accurate diagnosis of gastrointestinal complications during chemotherapy for acute myeloid leukemia. The leukemic infiltrtion of the digestive system may cause mucosal ulcers which can lead to bleeding or perforation. The immune system deficiency in this cohort of patients may result in necrotic enterocolitis (leukemic typhlitis), perianal inflammation, abscesses, and peritonitis. We describe a 37-year old male who presented in June 2004 with 2- month history of fever, weakness and sore throat, treated with antibiotic therapy. Physical examination demonstrated palor. The peripheral blood count at admittance was as follow: Hemoglobin 87 g/l, WBC 63 x109/l, and platelets 56 x109/l. The peripheral blood differential count showed: myeloblasts 4%, polymorphonuclear neutrophils (PMN) 20%, monocytes 60%, lymphocytes 16%. The diagnosis of acute myeloid leukemia (AML) was confirmed by bone marrow aspirate, which presented an almost total infiltration by monocytoid blasts, AML type M5 according to FAB classification. Immunophenotypic evaluation by flow cytometry showed that the blast cells reacted with antibodies to CD33, CD13, CD14, CD64, CD15, cytogenetics showed normal karyotype. Induction treatment consisting of cytarabine 2 x 200 mg intravenously in push on days 1-8, vepeside 200 mg i.v. on days 1-5, adriblastine 90 mgon days 1,3 and 5. On day 15 of chemotherapy the patient got fever 38.5oC, abdominal pain and diarrhea (10 stools daily). Broad-spectrum antibiotic therapy with ceftriaxone and amikacin was promptly instituted but condition worsened, abdominal pain extended to all abdomen while the fever and diarrhea persisted. Ultrasonography on day 18 documented bowel wall thickness of colic tract, part of duodenum and jejunum. Owing to suspicion of neutropenic enterocolitis, antibiotic therapy intensified with teicoplanin, fluconazole, metronidazole and pipril. Patient was neutropenic and thrombocytopenic, although daily platelet transfusion from a single donor were given. We started with granulocyte colony stimulating factor (G-CSF) 5 g/kg, which was adiminstered for 7 days. After 7 days neutrophil value reached 1x x109/l, but fever persisted, abdominal distension and diarrhea progressively improved. The fever peristed and central venous catheter was removed on day 30. After removal of the catheter the patient was getting better: the fever disappeared. The blood count showed Hb 91 g/l, WBC 3,4 x109/l, platelet 114 x109/l and normal leukocyte differential count. We emphesize the importance of collaboration between the hematologist and the surgeon in monitoring gastrointestinal complications during and after chemotherapy for acute leukemias and value of abdominal ultrasonography evaluation.
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González-Mazón, I., J. Rueda-Gotor, I. Ferraz-Amaro, L. Sanchez-Bilbao, F. Genre, V. Calvo-Río, S. Remuzgo-Martínez, et al. "POS0977 CARDIOVASCULAR AND DISEASE RELATED FEATURES IN AXIAL SPONDYLITIS WITH AND WITHOUT CONCOMITANT PSORIASIS. A MULTICENTER STUDY WITH 882 PATIENTS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 755.1–755. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2025.
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Background:Patients with axial spondyloarthritis (axSpA) may present with concomitant psoriasis (Ps) in approximately 10% of cases. As with axSpA, Ps is also associated with an accelerated atherosclerosis process1. However, it is unknown whether the presence of Ps confers an increased cardiovascular (CV) risk in patients with axSpA.Objectives:To compare factors related to the disease, CV risk factors, atherosclerotic burden, and CV events in patients with axSpA with and without Ps.Methods:Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA. We compared axSpA patients with and without concomitant psoriasis, focusing mainly on CV risk characteristics. Background information on CV risk factors, CV events, and disease-related factors was reviewed, and data on maximum body index, blood pressure, lipid profile, and disease status at the time of the study were also obtained. Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria.Results:A set of 882 axSpA patients were included. 786 (89.1%) of them had no concomitant Ps, which was present in 96 (10.9%) patients. Although the mean age was similar, male sex was more prevalent in axSpA patients with Ps (79.1% Vs 66.5%, p=0.01) (Table 1).Furthermore, it was found that axSpA with Ps had a more frequent history of synovitis (50% vs 33%, p = 0.001), dactylitis (13% vs 6%, p = 0.011) and concomitant inflammatory bowel disease (13% vs 6%, p = 0.01). AxSpA patients with Ps had a non-significant trend towards a higher prevalence of asymmetric sacroiliitis (23 vs 16%, p = 0.064) and had a lower frequency of positive HLA-B27 status (56% vs 72%, p = 0.003). Regarding the management of the disease, prednisone (23% vs 12%, p = 0.02), methotrexate (30% vs 15%, p = 0.000) and anti-TNFα therapy (50% vs 34%, p = 0.002) were more commonly used in the group with Ps.Regarding CV risk characteristics, no differences were observed either in the prevalence of traditional CV risk factors (Table 1), nor in the total serum level, HDL and LDL, blood pressure and body mass index at that time of the study. However, axSpA patients with Ps showed a higher prevalence of CV events (9% vs 4%, p = 0.05), including ischemic heart disease (6% vs 3%, p = 0.042) and ischemic stroke (4% vs 1%, p = 0.016) (Table 1). The subclinical atherogenic burden was also more severe in the group with Ps, with a higher prevalence of carotid plaques (39% vs 31%, p = 0.098), and higher values of cIMT (0.664 ± 0.170 mm vs 0.642 ± 0.142 mm, p = 0.16), although the differences did not reach statistical significance.Table 1.Main sociodemographic and cardiovascular differences among axSpA patients with and without psoriasis.axSpA without psoriasis (n=786)axSpA with psoriasis (n=96)pMen/Women, n523/26876/200.010Mean age (years) ±SD at the time of study49 ± 1349 ± 130.81AS/nr-AxSpa625/16677/190.79History of CV risk factors Current smokers267 (34)30 (31)0.60 Obesitty174 (22)26 (27)0.29 Dyslipidemia262 (33)35 (36)0.48 Hypertension211 (27)28 (29)0.57 Diabetes Mellitus56 (7)8 (8)0.65 Chronic Kidney Disease19 (2)3 (3)0.72History of cardiovascular events, n (%)33 (4)9 (9)0.023 Ischemic heart disease20 (3)6 (6)0.042 Congestive heart failure2 (0)1 (1)0.29 Ischemic stroke6 (1)4 (4)0.016 Peripheral artery disease6 (1)0 (0)0.99CV data at the time of studyCarotid plaques244 (31)38 (39)0.098IMT mm0.642 ± 0.1420.664 ± 0.1700.16IMT >= 900 mm40 (5)6 (6)0.66Abbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis.Conclusion:The presence of Ps may confer additional CV risk to axSpA patients and is associated with particular disease related factors.References:[1]Fang N, Jiang M, Fan Y. Association Between Psoriasis and Subclinical Atherosclerosis: A Meta-Analysis. Medicine (Baltimore). 2016;95(20):e3576.Disclosure of Interests:None declared.
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Sharma, Anchal, Aisha Qazi, Shubha Priyamvada, Anoop Kumar, Justin Ceh, Jeet Bhalala, Mohammed Alrubaee, et al. "FECAL METABOLOMIC ANALYSIS OF SERT DEFICIENT MICE UNDER BASAL CONDITIONS AND CHRONIC COLITIS." Inflammatory Bowel Diseases 27, Supplement_1 (January 1, 2021): S38—S39. http://dx.doi.org/10.1093/ibd/izaa347.095.
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Abstract Inflammatory bowel diseases (IBDs) are chronic inflammatory multifactorial diseases caused by genetic, immune, and environmental factors. A decrease in intestinal serotonin transporter (SERT), which controls the extracellular availability of serotonin (5-HT) has been implicated in IBD. We previously showed that SERT deletion in mice altered gut bacterial community structure. The gut microbiota-derived metabolites are functional intermediaries between the microbiota and host. Here, we investigated the impact of SERT deficiency on gut metabolites under basal conditions and chronic colitis mimicking human IBD. Methods: Global metabolic profiles were analyzed by “Metabolon” (Durham, NC) on fecal samples from wild type littermates (WT) and SERT KO mice given water or chronic DSS (2.5% DSS for 5 weeks, n=7–9/group). Data were analyzed by ANOVA contrasts (difference between groups) and by two-way ANOVA (P<0.05, q<0.01). Results: SERT KO exhibited more severe colitis vs WT as assessed by histological score, myeloperoxidase activity and colon length. There was more pronounced decrease in the mRNA of tight junction proteins (TJs) occludin-1 and ZO-1 in SERT KO DSS vs WT DSS intestine. Metabolic profiling revealed that SERT deficiency alone resulted in extremely low levels of fecal ectoine, a bacterial derived solute that maintains TJ proteins expression. DSS treatment of WT (but not SERT KO) resulted in a significant increase in microbial derived metabolites including phenylalanine, N-acetylphenylalanine, tyrosine derivatives, glutamate, glutamine and benzoate derivatives. An increase in Trimethylamine N-oxide (TMAO), the short chain fatty acids butyrate/isobutyrate, TCA cycle metabolites; and a decrease in several metabolites including spermidine and various primary and secondary bile acids occurred in DSS treated WT and SERT KO to varying degrees; suggesting that these pathways may contribute to the colitis severity in SERT KO mice. Several secondary bile acids, ketone bodies, the metabolites of pterin, riboflavin pathway (FAD and FMN) and fatty acid metabolism pathways were increased in SERT KO (basal and DSS) suggesting genotype related differences in microbial community. We recently showed an impairment of Aryl hydrocarbon receptor (AhR), an IBD susceptible gene, in SERT KO mice, which could be partly due to altered availability of ligands. Indeed, the bacterial derived AhR ligand tryptamine was extremely low in SERT KO (basal and DSS). DSS increased the host derived AhR ligand, kynurenine in WT, but not in SERT KO.Conclusion:These data highlight the impact of serotonergic machinery and SERT inhibition on host physiology and pathophysiology of IBD. The results provide unique insights into gut bacteria derived metabolites and may aid in the development of novel treatment for disorders with altered SERT and 5-HT availability (Supported by CCFA and NIH).