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Item Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study(Frontiers Media, 2020-11-16) Kawata, Keisuke; Steinfeldt, Jesse A.; Huibregtse, Megan E.; Nowak, Madeleine K.; Macy, Jonathan T.; Kercher, Kyle; Rettke, Devin J.; Shin, Andrea; Chen, Zhongxue; Ejima, Keisuke; Newman, Sharlene D.; Cheng, Hu; Medicine, School of MedicineWhile neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.Item Associations of chronic diarrhoea with non-alcoholic fatty liver disease and obesity-related disorders among US adults(BMJ, 2019-08-12) Shin, Andrea; Xu, Huiping; Imperiale, Thomas F.; Medicine, School of MedicineMechanisms explaining observed associations between diarrhoea and obesity or increased body mass index (BMI) are unclear. Objective: To assess associations of bowel patterns with BMI, metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD) and other obesity-related disorders. Design: We performed a cross-sectional analysis of data from adults who completed bowel health questions for the 2005 to 2010 cycles of the National Health and Nutrition Examination Surveys. Relationships were examined using multinomial logistic regression. Confounding effects of demographics, smoking, alcohol and BMI were examined by sequential modelling. Results: Among 13 413 adults, weighted prevalence rates of constipation and diarrhoea were 8.9% and 6.6%, respectively. Mean BMI was associated with bowel patterns (p<0.001), and was higher with diarrhoea (30.3 kg/m2) versus normal bowel patterns (28.6 kg/m2) and with diarrhoea versus constipation (27.8 kg/m2). NAFLD was more prevalent (ORs, 95% CI) in diarrhoea versus normal bowel patterns (OR=1.34, 95% CI 1.01 to 1.78) or constipation (OR=1.45, 95% CI 1.03, 2.03) in adjusted analyses. The higher prevalence of MS in diarrhoea versus constipation (OR=1.27, 95% CI 0.97 to 1.67) was not independent of BMI. Conclusions: These findings suggest an association between diarrhoea and NAFLD that is independent of BMI.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 Associations of Food Intolerance with Irritable Bowel Syndrome, Psychological Symptoms, and Quality of Life(Elsevier, 2022) Jansson-Knodell, Claire L.; White, Mattie; Lockett, Carolyn; Xu, Huiping; Shin, Andrea; Medicine, School of MedicineBackground & aims: The impact of different types of food intolerance on gastrointestinal symptoms and quality of life (QOL) is poorly understood. We aimed to investigate associations of food intolerance and type of intolerance with irritable bowel syndrome (IBS), health-related QOL, and psychological symptoms. Methods: We conducted an observational study of United States-based adults through an online survey. Demographics, culprit foods, symptoms, medical evaluation, Rome IV criteria for IBS, health-related QOL (Short-Form Health Survey 12), and anxiety and depression scores (Hospital Anxiety and Depression Scale) were collected in participants with self-reported food intolerance (lactose, non-lactose food, lactose plus food intolerance), and controls with no intolerance. Univariable associations of group with study endpoints were analyzed with the Kruskal-Wallis and Pearson χ2 or Fisher exact test. Multivariable comparisons were analyzed by logistic and linear regression. Results: A total of 197 patients with (59 lactose, 61 non-lactose food, 77 lactose plus food intolerance) and 273 patients without intolerance participated. Lactose, wheat, and eggs were the most common food triggers. Gas (54.2%), abdominal pain (40.2%), and diarrhea (37.3%) were frequently reported symptoms of food intolerance. Reactions caused 57.8% to eliminate the food. Rates of IBS, abnormal anxiety scores, and abnormal depression scores were highest in lactose plus food intolerance; Short-Form Health Survey 12 scores were lowest in lactose plus food intolerance. Multivariable analyses revealed all intolerance subgroups were more likely to have IBS than controls. Conclusions: Food intolerance is associated with IBS, anxiety, depression, and decreased health-related QOL and frequently leads to food elimination. Adults with lactose and lactose plus food intolerance have higher rates of IBS, increased psychological symptoms, and poorer QOL.Item Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome(Wolters Kluwer, 2022) Calderon, Gerardo; Patel, Chirag; Camilleri, Michael; James-Stevenson, Toyia; Bohm, Matthew; Siwiec, Robert; Rogers, Nicholas; Wo, John; Lockett, Carolyn; Gupta, Anita; Xu, Huiping; Shin, Andrea; Medicine, School of MedicineBackground goals: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). Study: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. Results: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. Conclusions: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.Item Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis(BMJ, 2017) Nelson, Alfred D.; Camilleri, Michael; Chirapongsathorn, Sakkarin; Vijayvargiya, Priya; Valentin, Nelson; Shin, Andrea; Erwin, Patricia J.; Wang, Zhen; Murad, M. Hassan; Department of Medicine, IU School of MedicineObjective To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. Data sources We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. Study selection Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. Data extraction and synthesis Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. Outcomes Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. Results Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. Conclusions Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC.Item COVID-19 Epidemiology and Google Searches(Elsevier, 2020-10-14) Jansson-Knodell, Claire L.; Bhavsar-Burke, Indira; Shin, Andrea; Medicine, School of MedicineWe read “Increased internet search interest for GI symptoms may predict COVID-19 cases in US hotspots” by Ahmad et al with interest. The authors compared search volume for gastrointestinal (GI) symptoms with coronavirus disease 2019 (COVID-19) incidence in 15 states to observe that searches for the terms ageusia, loss of appetite, and diarrhea correlated with disease burden at 4 weeks. In our own analysis of Google Trends, we made similar observations with a few distinctions. We assessed COVID-19 plus diarrhea searches and United States COVID-19 epidemiology by using the Pearson correlation coefficient. We used Centers for Disease Control and Prevention (CDC) data for reported incidence and mortality (deaths per capita), cross-referencing with U.S. census data.Our findings suggest that diarrhea searches do not correlate well with disease burden; however, although analysis of online searches for GI symptoms and COVID-19 is not likely to be a good substitute for more traditional epidemiologic methods, search activity could still be useful as part of a more complex model. As you have concluded, Google Trends is a valuable tool, and it is our responsibility to carefully understand and refine its role in this global pandemic.Item Delayed Gastric Emptying Is Not Associated with a Microbiological Diagnosis of Small Intestinal Bacterial Overgrowth(Springer, 2021) Calderon, Gerardo; Siwiec, Robert M.; Bohm, Matthew E.; Nowak, Thomas V.; Wo, John M.; Gupta, Anita; Xu, Huiping; Shin, Andrea; Medicine, School of MedicineBackground: Clinical symptoms of patients with small intestinal bacterial overgrowth (SIBO) may overlap with symptoms of gastroparesis. Prior studies suggest delayed small intestinal transit is associated with SIBO, but have not shown an association between delayed gastric emptying and SIBO. However, these studies have generally relied on the indirect method of breath testing to diagnose SIBO. Aims: The aim of this study was to examine the association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Methods: In a single-center retrospective study of previous research participants who presented for small bowel enteroscopy for diagnostic evaluation of SIBO, we identified 73 participants who underwent gastric emptying study by scintigraphy. A microbiological diagnosis of SIBO was made in patients based on culture results of jejunal aspirates. Clinical symptoms were assessed using the total gastroparesis cardinal symptom index (GCSI) score. We compared delayed gastric emptying, 2- and 4-h gastric retention, and gastroparesis symptoms between patients with and without a microbiological diagnosis of SIBO. Key results: Among 29 participants with SIBO and 44 without SIBO, 33 (45%) had evidence of delayed gastric emptying. There was no significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Percent retained at 2 and 4 h, and total GCSI scores did not differ significantly between those with and without SIBO. Conclusions: Although delayed gastric emptying is common in patients with suspected SIBO, gastric emptying is not associated with a microbiological diagnosis of SIBO.Item Early Adverse Life Events and Post-Traumatic Stress Disorder in Patients with Constipation and Suspected Disordered Defecation(Wiley, 2022) Hendrix, Justin; Ranginani, Dheeksha; Montero, Anne Mary; Lockett, Carolyn; Xu, Huiping; James-Stevenson, Toyia; Shin, Andrea; Medicine, School of MedicineBackground: Early adverse life events (EALs) and post-traumatic stress disorder (PTSD) are associated with irritable bowel syndrome (IBS). Disordered defecation (DD) presents with symptoms of IBS or functional constipation (FC) and is associated with psychological distress. However, the role of trauma and stress in chronic constipation is poorly defined. We aimed to examine EALS, PTSD, and psychological symptoms in patients with constipation and suspected DD. Methods: We conducted a survey study among adults with constipation who completed anorectal manometry (ARM) and balloon expulsion testing (BET). Data were collected on socio-demographics, EALs, PTSD, bowel symptoms, quality of life, and anxiety and depression. We performed comparisons between individuals with normal versus abnormal ARM or BET, subgroup analysis by detailed ARM and BET findings, and latent class analysis using individual EAL domains. Key results: Among 712 eligible patients, 69 completed the study. EALs and provisional PTSD were present in 75.4% and 27.5%, respectively; rates did not differ between those with normal versus abnormal ARM or BET. Normal testing was associated with higher rates of specific EAL domains (emotional abuse and mental illness), higher depression scores, and poorer mental component scores in both primary and subgroup comparisons (all p < 0.05). Normal testing was associated with a lower likelihood of high-EAL latent class (p = 0.01) membership. Presence of IBS or FC did not influence associations. Conclusions & inferences: Early adverse life events and PTSD are prevalent in patients with constipation and suspected DD. Those with normal ARM and BET have higher rates of prior emotional abuse and poorer mental health.Item Effects of Irritable Bowel Syndrome on Daily Activities Vary Among Subtypes Based on Results From the IBS in America Survey(Elsevier, 2019-11) Ballou, Sarah; McMahon, Courtney; Lee, Ha-Neul; Katon, Jesse; Shin, Andrea; Rangan, Vikram; Singh, Prashant; Nee, Judy; Camilleri, Michael; Lembo, Anthony; Iturrino, Johanna; Medicine, School of MedicineBackground & Aims Irritable bowel syndrome (IBS) is associated with significant disease burden and decreased quality of life (QOL). We investigated the effects of IBS on different areas of daily function and compared these among disease subtypes. Methods The Life with IBS survey was conducted by Gfk Public Affairs & Corporate Communications from September through October 2015. Respondents met Rome III criteria for constipation-predominant or diarrhea-predominant IBS (IBS-C and IBS-D, respectively). Data were collected from 3254 individuals (mean age, 47 years; 81% female; and 90% Caucasian) who met IBS criteria. Results Respondents who were employed or in school (n = 1885) reported that IBS symptoms affected their productivity an average of 8.0 days out of the month and they missed approximately 1.5 days of work/school per month because of IBS. More than half the individuals reported that their symptoms were very bothersome. Individuals with IBS-C were more likely than with IBS-D to report avoiding sex, difficulty concentrating, and feeling self-conscious. Individuals with IBS-D reported more avoidance of places without bathrooms, difficulty making plans, avoiding leaving the house, and reluctance to travel. These differences remained when controlling for symptom bothersomeness, age, sex, and employment status. In exchange for 1 month of relief from IBS, more than half of the sample reported they would be willing to give up caffeine or alcohol, 40% would give up sex, 24.5% would give up cell phones, and 21.5% would give up the internet for 1 month. Conclusions Although the perceived effects of IBS symptoms on productivity are similar among its subtypes, patients with IBS-C and IBS-D report differences in specific areas of daily function.
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