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Item Associations between Household-Level Exposures and All-Cause Diarrhea and Pathogen-Specific Enteric Infections in Children Enrolled in Five Sentinel Surveillance Studies(MDPI, 2020-11) Colston, Josh M.; Faruque, Abu S. G.; Hossain, M. Jahangir; Saha, Debasish; Kanungo, Suman; Mandomando, Inácio; Nisar, M. Imran; Zaidi, Anita K. M.; Omore, Richard; Breiman, Robert F.; Sow, Samba O.; Roose, Anna; Levine, Myron M.; Kotloff, Karen L.; Ahmed, Tahmeed; Bessong, Pascal; Bhutta, Zulfiqar; Mduma, Estomih; Penatero Yori, Pablo; Sunder Shrestha, Prakash; Olortegui, Maribel P.; Kang, Gagandeep; Lima, Aldo A. M.; Humphrey, Jean; Prendergast, Andrew; Schiaffino, Francesca; Zaitchik, Benjamin F.; Kosek, Margaret N.; Medicine, School of MedicineDiarrheal disease remains a major cause of childhood mortality and morbidity causing poor health and economic outcomes. In low-resource settings, young children are exposed to numerous risk factors for enteric pathogen transmission within their dwellings, though the relative importance of different transmission pathways varies by pathogen species. The objective of this analysis was to model associations between five household-level risk factors—water, sanitation, flooring, caregiver education, and crowding—and infection status for endemic enteric pathogens in children in five surveillance studies. Data were combined from 22 sites in which a total of 58,000 stool samples were tested for 16 specific enteropathogens using qPCR. Risk ratios for pathogen- and taxon-specific infection status were modeled using generalized linear models along with hazard ratios for all-cause diarrhea in proportional hazard models, with the five household-level variables as primary exposures adjusting for covariates. Improved drinking water sources conferred a 17% reduction in diarrhea risk; however, the direction of its association with particular pathogens was inconsistent. Improved sanitation was associated with a 9% reduction in diarrhea risk with protective effects across pathogen species and taxa of around 10–20% risk reduction. A 9% reduction in diarrhea risk was observed in subjects with covered floors, which were also associated with decreases in risk for zoonotic enteropathogens. Caregiver education and household crowding showed more modest, inconclusive results. Combining data from diverse sites, this analysis quantified associations between five household-level exposures on risk of specific enteric infections, effects which differed by pathogen species but were broadly consistent with hypothesized transmission mechanisms. Such estimates may be used within expanded water, sanitation, and hygiene (WASH) programs to target interventions to the particular pathogen profiles of individual communities and prioritize resources.Item Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome(Wolters Kluwer, 2023-01-01) Waseem, Mohammed Ray; Shin, Andrea; Siwiec, Robert; James-Stevenson, Toyia; Bohm, Matthew; Rogers, Nicholas; Wo, John; Waseem, Lina; Gupta, Anita; Jarrett, Megan; Kadariya, Jhalka; Xu, Huiping; Medicine, School of MedicineIntroduction: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. Methods: We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. Results: Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [-0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). Discussion: Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.Item Characterization of the STII transposon and determination of its role in human diarrhea(1988) Hu, Shiau-TingItem Immune Checkpoint Inhibitor-Induced Colitis Presenting As Lymphocytic Colitis(Cureus, 2021-09-18) Khan, Jaffar; Katona, Terrence; Pathology and Laboratory Medicine, School of MedicineCheckpoint inhibitors (CPIs) are a new class of drugs that have changed the treatment and prognosis of several malignancies, even in their advanced stages. These drugs have increased patient survival rates. CPIs stimulate the immune system and include cytotoxic T-lymphocyte antigen-4 inhibitors (ipilimumab), programmed cell death inhibitors such as pembrolizumab, nivolumab, and avelumab, and programmed cell death protein ligand-1 inhibitors such as atezolizumab. Herein, we present a case of CPI-induced colitis in a 45-year-old woman with a history of melanoma. The melanoma was BRAF-positive with a V600 mutation. She had metastasis to the brain and the right 10th rib, which underwent surgery and radiation treatment, respectively. She was treated with nivolumab and denosumab. The patient presented with chronic watery diarrhea. Biopsy revealed lymphocytic colitis-like changes in the colon and terminal ileum. Thus, given the history of CPIs, a diagnosis of CPIS-induced colitis was made.Item Indiana State Board of Health Monthly Bulletin, 1905 Vol. 7 No. 3(1905) Quick, W.R.Item Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: A cross-over randomized controlled trial(Frontiers Media, 2023-01-04) Yoosuf, Shakira; Barrett, Caitlin G.; Papamichael, Konstantinos; Madoff, Sarah E.; Kurada, Satya; Hansen, Joshua; Silvester, Jocelyn A.; Therrien, Amelie; Singh, Prashant; Dennis, Melinda; Leffler, Daniel A.; Kelly, Ciaran P.; Medicine, School of MedicineBackground: Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD. Methods: Prospective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015. Results: Twelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (-0.03 versus -0.26; P = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, P = 0.004), abdominal pain (2.92 versus 2.42, P = 0.009), and diarrhea sub-scores (3.44 versus 2.92, P = 0.037) during the run-in period with omeprazole. Conclusion: In this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.Item Photo quiz: Diarrhea and fever in a child returning from Africa. Answer to photo quiz: Enteric fever(American Society for Microbiology, 2015-04) Relich, Ryan F.; Manaloor, John J.; Fox, Thomas G.; Department of Pathology & Laboratory Medicine, IU School of Medicine