| 1. |
- Ek, Weronica E, et al.
(författare)
-
Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
- 2013
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
-
Tidskriftsartikel (refereegranskat)abstract
- Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were twosided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10-9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10-7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10-6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. © The Author 2013.
|
|
| 2. |
- Tack, Jan, 1962, et al.
(författare)
-
A survey on the impact of the COVID-19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase
- 2020
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background The COVID-19 pandemic, declared by WHO on March 13, 2020, had a major global impact on the healthcare system and services. In the acute phase, the presence of the SARS-CoV-2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety-focused approach with adequate infection prevention for patients and healthcare professionals. Methods We summarized knowledge on the presence of the SARS-CoV-2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center. Results Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol-borne infection of healthcare workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly. Conclusions and Inferences Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID-19 pandemic era, to guarantee a high-quality patient care with adequate infection prevention.
|
|
| 3. |
- Simrén, Magnus, 1966, et al.
(författare)
-
Nutritional aspects in patients with functional gastrointestinal disorders and motor dysfunction in the gut. Working team report of the Swedish Motility Group (SMoG).
- 2007
-
Ingår i: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. - : Elsevier BV. - 1590-8658. ; 39:5, s. 495-504
-
Forskningsöversikt (refereegranskat)abstract
- In reviews regarding the management of patients with functional gastrointestinal disorders and motility disturbances within the gut nutritional aspects and dietary advice is often put forward as being of great importance. However, there are relatively few high-quality, interventional studies in the literature supporting an important role for general dietary advice to improve symptoms in these patients. Nutritional supplementation to patients with malnutrition due to severe dysfunction of the gastrointestinal tract is of course less controversial, even though different views on how this should be performed exist. The content of this article is based on presentations given by the authors during the second meeting of the Swedish Motility Group held in Gothenburg in March 2005, and aims to give an overview on the role of dietary advice and nutritional supplementation to patients with gastrointestinal dysfunction of different severity.
|
|
| 4. |
- Staller, K., et al.
(författare)
-
Mortality risk in irritable bowel syndrome: Results from a nationwide prospective cohort study
- 2020
-
Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 115:5, s. 746-755
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Mortality concern is a frequent driver of care seeking in patients with irritable bowel syndrome (IBS). Data on mortality in IBS are scarce, and population-based studies have been limited in size. We examined mortality in IBS. METHODS: A nationwide, matched, population-based cohort study was conducted in Sweden. We identified 45,524 patients undergoing a colorectal biopsy at any of Sweden’s 28 pathology departments and with a diagnosis of IBS from 2002 to 2016 according to the National Patient Register, a nationwide registry of inpatient and outpatient specialty care. We compared the mortality risk between these individuals with IBS and age- and sex-matched reference individuals (n 5 217,316) from the general population and siblings (n 5 53,228). In separate analyses, we examined the role of mucosal appearance for mortality in IBS. Finally, we examined mortality in 41,427 patients with IBS not undergoing a colorectal biopsy. Cox regression estimated hazard ratios (HRs) for death. RESULTS: During follow-up, there were 3,290 deaths in individuals with IBS (9.4/1,000 person-years) compared with 13,255 deaths in reference individuals (7.9/1,000 person-years), resulting in an HR of 1.10 (95% confidence interval [CI] 5 1.05–1.14). After adjustment for confounders, IBS was not linked to mortality (HR 5 0.96; 95% CI 5 0.92–1.00). The risk estimates were neutral when patients with IBS were compared with their siblings. The underlying mucosal appearance on biopsy had only a marginal impact on mortality, and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR 5 1.02; 95% CI 5 0.99–1.06). DISCUSSION: IBS does not seem to confer an increased risk of death. Copyright © 2020 by The American College of Gastroenterology.
|
|
| 5. |
|
|
| 6. |
- Bennet, Sean, et al.
(författare)
-
Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation
- 2018
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 30:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms. Methods Key Results Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed. Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity. Conclusions & Inferences This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.
|
|
| 7. |
- Berman, Anne H., et al.
(författare)
-
Reducing Risky Alcohol Use via Smartphone App Skills Training Among Adult Internet Help-Seekers : A Randomized Pilot Trial
- 2020
-
Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol is one of the leading risk factors for global disease burden and overconsumption leads to a wide variety of negative consequences in everyday life. Digital interventions have shown small positive effects in contributing to reductions in problematic use. Specific research on smartphone apps is sparse and the few studies published indicate effects ranging from negative or null to small or moderate. TeleCoach™, a web-based skills training smartphone app, has shown positive effects in non-treatment-seeking university students with excessive drinking. This pilot trial aimed to evaluate app effects in a sample of internet help-seekers from the general population in Sweden. A total of 89 participants were recruited via online advertisement. Following baseline assessment for hazardous use, they were randomized to TeleCoach or a web-based control app offering brief information and advice regarding problematic alcohol use. The primary outcome was number of standard drinks per week; secondary outcomes included drinking quantity and frequency, binge drinking and blood alcohol count measures as well as app user data and comorbidity related to depression, anxiety, and drug use. Analysis of baseline and 6-week follow-up outcomes showed significant within-group effects on alcohol consumption but no significant between-group differences. Effect sizes for the within-group changes in the primary outcome over time were significant [F(1, 55)=43.98; p < 0.001], with a Cohen's d of 1.37 for the intervention group and 0.92 for the control group. This difference in effect sizes indicated that continuation of the study as a large randomized, controlled trial with up to 1,000 participants could be worthwhile.
|
|
| 8. |
- Berman, Anne H., et al.
(författare)
-
Skills Training for Reducing Risky Alcohol Use in App Form Among Adult Internet Help-seekers
- 2020
-
Ingår i: Annals of Behavioral Medicine. - : Oxford University Press. - 0883-6612 .- 1532-4796. ; 54:S1, s. S417-S417
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Problematic alcohol use in Sweden occurs among 16 % of the adult population. Digital interventions of varying intensity have shown positive effects in contributing to reductions in problematic use, and the TeleCoach app has shown positive effects in non-treatment-seeking university students with excessive drinking (Gajecki et al., 2017). This pilot study evaluated the app among adult internet help-seekers, and motivated continued data collection in the current target group. Methods: Adult internet-help seekers, recruited via advertisement, were included if they scored ³6 (women) or ³8 (men) on the Alcohol Use Disorders Identification Test (AUDIT). Those with depression scores of ³31 on the Montgomery Åsberg Depression Rating Scale (MADRS-S) or problematic drug use scores of ³8 on the Drug Use Disorders Identification Test (DUDIT) were contacted for a telephone interview and included following clinical assessment; if not reached they were excluded. Participants randomized at a 1:1 ratio to the TeleCoach™ web-based app or to a web-based app with information texts from primary care-based self-help material for changing problematic alcohol use. At six-week follow-up, the primary outcome was the number of standard drinks per past week (Timeline-Followback). Results: Of 147 persons assessed for eligibility, 89 were assigned to the intervention group (n=42) or control group (n=47). Average AUDIT levels at baseline were ³18.The baseline number of standard drinks per week was 32.73 (SD 21.16) for the intervention group, and 26 (4.08) for the control group; at 6-week follow-up it was 12.73 (10.52) and 13.48 (11.13) for the intervention and control groups, respectively. No significant between-groups effects occurred, but withingroup changes over time were significant (F(1, 55)=43.98; p< 0.000), with an effect size of 1.37 for the intervention group and 0.92 for the control group. Conclusions: The results suggest that web-based apps can be of help to internet help-seekers motivated to reduce problematic alcohol use. We have proceeded with the planned larger randomized, controlled study and will present 6-week follow-up data for the entire study sample (n=∼1000) in this presentation.
|
|
| 9. |
- Bonfiglio, F., et al.
(författare)
-
A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population
- 2017
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:2
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundGastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. MethodsWe performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). Key resultsWe identified 30 GERD suggestive risk loci (P5x10(-5)), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. ConclusionsWe report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.
|
|
| 10. |
- Farre, R., et al.
(författare)
-
In Functional Dyspepsia, Hypersensitivity to Postprandial Distention Correlates With Meal-Related Symptom Severity
- 2013
-
Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 145:3, s. 566-573
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Hypersensitivity to gastric distention, an important feature of functional dyspepsia, is assessed by stepwise balloon distention of the proximal stomach in fasting patients. However, symptoms of functional dyspepsia are often worse after a meal, so studies of postprandial balloon distentions might be more relevant. We compared the effects of fasting and postprandial stomach distention in patients with functional dyspepsia. METHODS: Twenty healthy controls and 62 patients with functional dyspepsia participated in a gastric barostat study at Leuven University Hospital with graded isobaric distentions before and after a liquid meal. On a separate day, all patients underwent a gastric emptying breath test with assessment of postprandial severity of 6 different dyspeptic symptoms scored at 15-minute intervals for 4 hours. For each symptom, a meal-related severity score was obtained by adding all scores; the cumulative symptom score (CSS) was obtained by adding individual symptom severity scores. RESULTS: In patients, but not in controls, postprandial sensitivity to balloon distention was significantly greater than fasting sensitivity. The CSS and individual symptom scores did not differ between patients with normal or hypersensitivity to fasting distention, but patients who were hypersensitive to postprandial distention had a significantly higher CSS, along with scores for postprandial fullness, bloating, and nausea (all P < .05). On multivariate analysis, hypersensitivity to postprandial distention was associated with hypersensitivity to fasting distention and with impaired accommodation to a meal. CONCLUSIONS: Postprandial, but not fasting, distention thresholds are related to the severity of meal-related symptoms in patients with functional dyspepsia.
|
|
| 11. |
- Grinsvall, Cecilia, et al.
(författare)
-
Altered Structural Covariance of Insula, Cerebellum and Prefrontal Cortex Is Associated with Somatic Symptom Levels in Irritable Bowel Syndrome (IBS)
- 2021
-
Ingår i: Brain Sciences. - 2076-3425. ; 11:12
-
Tidskriftsartikel (refereegranskat)abstract
- Somatization, defined as the presence of multiple somatic symptoms, frequently occurs in irritable bowel syndrome (IBS) and may constitute the clinical manifestation of a neurobiological sensitization process. Brain imaging data was acquired with T1 weighted 3 tesla MRI, and gray matter morphometry were analyzed using FreeSurfer. We investigated differences in networks of structural covariance, based on graph analysis, between regional gray matter volumes in IBS-related brain regions between IBS patients with high and low somatization levels, and compared them to healthy controls (HCs). When comparing IBS low somatization (N = 31), IBS high somatization (N = 35), and HCs (N = 31), we found: (1) higher centrality and neighbourhood connectivity of prefrontal cortex subregions in IBS high somatization compared to healthy controls; (2) higher centrality of left cerebellum in IBS low somatization compared to both IBS high somatization and healthy controls; (3) higher centrality of the anterior insula in healthy controls compared to both IBS groups, and in IBS low compared to IBS high somatization. The altered structural covariance of prefrontal cortex and anterior insula in IBS high somatization implicates that prefrontal processes may be more important than insular in the neurobiological sensitization process associated with IBS high somatization. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
|
|
| 12. |
- Grinsvall, Cecilia, et al.
(författare)
-
Association between pain sensitivity and gray matter properties in the sensorimotor network in women with irritable bowel syndrome
- 2021
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background Enhanced perception of visceral stimuli is an important feature of Irritable Bowel Syndrome (IBS), but it is not known whether visceral sensitivity is associated with regional structural brain properties in IBS. Methods Structural brain magnetic resonance imaging data from 216 women with IBS and 138 healthy women were parcellated with FreeSurfer to define regional gray matter morphometry (volume, cortical thickness, surface area and mean curvature) in the sensorimotor network. General linear models were used to detect group differences between IBS and health. In a second set of 48 female IBS patients, pain threshold, pain intensity ratings during rectal balloon distension, and reported levels of abdominal pain and bloating were correlated with brain regions that showed differences between IBS and health in the first data set. Key Results Several statistically significant differences between IBS patients and healthy controls were found, mainly higher gray matter volume and cortical thickness in primary somatosensory cortex, secondary somatosensory cortex, and subcortical regions, and lesser gray matter volume, surface area and cortical thickness in posterior insula and superior frontal gyrus. Pain intensity ratings during rectal distension were associated with left primary somatosensory cortical thickness, and pain threshold was associated with right nucleus accumbens volume. Conclusions and Inferences Regional gray matter differences in sensorimotor network are associated with visceral sensitivity and may represent neuroplastic changes in female IBS patients.
|
|
| 13. |
|
|
| 14. |
- Huang, I. H., et al.
(författare)
-
Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis
- 2022
-
Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 10:8, s. 888-897
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives The global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real-world evidence of this gastroparesis-like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis. Methods In the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut-brain interaction via Internet. We selected subjects with gastroparesis-like symptoms (GPLS) (nausea and/or vomiting >= 1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self-induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global-10), symptoms of anxiety and depression (PHQ-4), somatic symptoms (PHQ-12), and healthcare utilization. Results The global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non-gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms. Conclusions GPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption.
|
|
| 15. |
- Kano, M., et al.
(författare)
-
Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.
|
|
| 16. |
- Keller, J., et al.
(författare)
-
Advances in the diagnosis and classification of gastric and intestinal motility disorders
- 2018
-
Ingår i: Nature Reviews Gastroenterology & Hepatology. - : Springer Science and Business Media LLC. - 1759-5045 .- 1759-5053. ; 15:5, s. 291-308
-
Tidskriftsartikel (refereegranskat)abstract
- Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5-10 years have led to this update about indications for and selection and performance of currently available tests. As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres. This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.
|
|
| 17. |
- Lagerlöf, E, et al.
(författare)
-
ABC om - IBS – irritabel tarm
- 2018
-
Ingår i: Lakartidningen. - 1652-7518. ; 115
-
Tidskriftsartikel (refereegranskat)
|
|
| 18. |
- Liljeruhm, Josefine, et al.
(författare)
-
Engineering a palette of eukaryotic chromoproteins for bacterial synthetic biology
- 2018
-
Ingår i: Journal of Biological Engineering. - : BIOMED CENTRAL LTD. - 1754-1611. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Coral reefs are colored by eukaryotic chromoproteins (CPs) that are homologous to green fluorescent protein. CPs differ from fluorescent proteins (FPs) by intensely absorbing visible light to give strong colors in ambient light. This endows CPs with certain advantages over FPs, such as instrument-free detection uncomplicated by ultra-violet light damage or background fluorescence, efficient Forster resonance energy transfer (FRET) quenching, and photoacoustic imaging. Thus, CPs have found utility as genetic markers and in teaching, and are attractive for potential cell biosensor applications in the field. Most near-term applications of CPs require expression in a different domain of life: bacteria. However, it is unclear which of the eukaryotic CP genes might be suitable and how best to assay them.Results: Here, taking advantage of codon optimization programs in 12 cases, we engineered 14 CP sequences (meffRed, eforRed, asPink, spisPink, scOrange, fwYellow, amilGFP, amajLime, cjBlue, mefiBlue, aeBlue, amilCP, tsPurple and gfasPurple) into a palette of Escherichia coil BioBrick plasmids. BioBricks comply with synthetic biology's most widely used, simplified, cloning standard. Differences in color intensities, maturation times and fitness costs of expression were compared under the same conditions, and visible readout of gene expression was quantitated. A surprisingly large variation in cellular fitness costs was found, resulting in loss of color in some overnight liquid cultures of certain high-copy-plasmid-borne CPs, and cautioning the use of multiple CPs as markers in competition assays. We solved these two problems by integrating pairs of these genes into the chromosome and by engineering versions of the same CP with very different colors.Conclusion: Availability of 14 engineered CP genes compared in E coil, together with chromosomal mutants suitable for competition assays, should simplify and expand CP study and applications. There was no single plasmid-borne CP that combined all of the most desirable features of intense color, fast maturation and low fitness cost, so this study should help direct future engineering efforts.
|
|
| 19. |
- McCulloch, Sofia, et al.
(författare)
-
The diagnostic value of a change in bowel habit for colorectal cancer within different age groups
- 2020
-
Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 8:2, s. 211-219
-
Tidskriftsartikel (refereegranskat)abstract
- Background Change in bowel habit as a sole alarm symptom for colorectal cancer is disputed. Objective We investigated the diagnostic value of change in bowel habit for colorectal cancer, particularly as a single symptom and within different age groups. Methods This retrospective cohort study examined colorectal cancer fast track referrals and outcomes across four Swedish hospitals (April 2016-May 2017). Entry criteria constituted one or more of three alarm features: anaemia, visible rectal bleeding, or change in bowel habit for more than 4 weeks in patients over 40 years of age. Patients were grouped as having only change in bowel habit, change in bowel habit plus anaemia/bleeding or anaemia/bleeding only. Results Of 628 patients, 22% were diagnosed with colorectal cancer. There were no cases of colorectal cancer in the only change in bowel habit group under 55 years, while this was 6% for 55-64 years, 8% for 65-74 years and 14% for 75 years and older. Among subjects under 55 years, 2% with anaemia/bleeding had colorectal cancer, this increased to 34% for 55 years and older (P < 0.0001). Change in bowel habit plus anaemia/bleeding gave a colorectal cancer prevalence of 16% in under 55 years and increased to 30% for 55 years and older (P = 0.07). Conclusion Change in bowel habit as the only alarm feature has a low diagnostic yield for colorectal cancer in patients under 55 years.
|
|
| 20. |
- Moraes Holst, Luiza, et al.
(författare)
-
Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
- 2022
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:24
-
Tidskriftsartikel (refereegranskat)abstract
- Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
|
|
| 21. |
|
|
| 22. |
- Parker, S., et al.
(författare)
-
Functional Gastrointestinal Disorders and Associated Health Impairment in Individuals with Celiac Disease
- 2022
-
Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 20:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Individuals with celiac disease (CD) can experience persisting gastrointestinal symptoms despite adhering to a gluten-free diet (GFD). This may be due to functional gastrointestinal disorders (FGIDs), although there is little data on its prevalence and associated factors. Methods: An online health questionnaire was completed by adult members of Celiac UK in October 2018. The survey included validated questions on Rome IV FGIDs, nongastrointestinal somatic symptoms, anxiety, depression, quality of life, health care use, GFD duration, and its adherence using the celiac dietary adherence test score (with a value ≤ 13 indicating optimal adherence). The prevalence of FGIDs and associated health impairment in the celiac cohort was compared against an age- and sex-matched population-based control group. Results: Of the 863 individuals with CD (73% female; mean age, 61 years), all were taking a GFD for at least 1 year, with 96% declaring that they have been on the diet for 2 or more years (2–4 years, 20%; ≥5 years, 76%). The adherence to a GFD was deemed optimal in 61% (n = 523), with the remaining 39% (n = 340) nonadherent. Those adhering to a GFD fulfilled criteria for a FGID in approximately one-half of cases, although this was significantly lower than nonadherent subjects (51% vs 75%; odds ratio [OR], 2.0; P < .001). However, the prevalence of FGIDs in GFD-adherent subjects was significantly higher than in matched population-based controls (35%; OR, 2.0; P < .001). This was accounted for by functional bowel (46% vs 31%; OR, 1.9; P < .0001) and anorectal disorders (14.5% vs 9.3%; OR, 1.7; P = .02) but not functional esophageal (7.6% vs 6.1%; P = .36) or gastroduodenal disorders (8.7% vs 7.4%; P = .47). Finally, GFD-adherent subjects with FGIDs were significantly more likely than their counterparts without FGIDs to have abnormal levels of anxiety (5% vs 2%; OR, 2.8; P = .04), depression (7% vs 2%; OR, 3.6; P = .01), somatization (31% vs 8%; OR, 5.1; P < .0001), and reduced quality of life (P < .0001). Conclusion: One in 2 people with CD, despite having been on a GFD for a number of years and demonstrating optimal adherence, have ongoing symptoms compatible with a Rome IV FGID. This is 2-fold the odds of FGIDs seen in age- and sex-matched controls. The presence of FGIDs is associated with significant health impairment, including psychological comorbidity. Addressing disorders of gut-brain interaction might improve outcomes in this specific group of patients. © 2021 AGA Institute
|
|
| 23. |
|
|
| 24. |
- Staller, Kyle, et al.
(författare)
-
Antibiotic use as a risk factor for irritable bowel syndrome: Results from a nationwide, case–control study
- 2023
-
Ingår i: Alimentary Pharmacology and Therapeutics. - 0269-2813 .- 1365-2036. ; 58:11-12, s. 1175-1184
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population-based investigation. Methods: A case–control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS. Results: Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14–2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1–2 (OR 1.67, 95% CI 1.61–1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24–3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class. Conclusions: Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations.
|
|
| 25. |
- Sundin, Johanna, et al.
(författare)
-
Colonic mast cell numbers, symptom profile, and mucosal expression of elements of the epithelial barrier in irritable bowel syndrome
- 2019
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background This study aimed to determine whether patients with IBS displayed altered mucosal mast cell (MC) numbers and proportions of MCs co-localizing with nerves compared with healthy subjects (HS) and whether these MC characteristics correlated with IBS symptoms, elements of the epithelial barrier, or visceral sensitivity. Methods Mucosal MC characteristics were determined using immunoassay. IBS symptoms, gene expression of elements of the epithelial barrier, fecal serine protease activity, and visceral sensitivity were assessed. Key Results The MC numbers per mm(2) were 2.0 (0.0-6.0) in patients with IBS (n = 43) and 3.5 (1.1-9.1) in HS (n = 20, P = .26). Of these, MCs were 0.0 (0.0-20) % vs 3.1 (0.0-18) % (P = .76) in IBS and HS, respectively, in co-localization with nerve fibers. MC characteristics were equivalent in the different IBS subtypes. Hierarchical cluster analysis identified two distinct groups among patients with IBS: MC high (higher MC numbers and proportions of MCs co-localizing with nerves) and MC low (lower MC numbers and proportions of MCs co-localizing with nerves). The MC high and MC low groups could not be discriminated with regard to IBS symptoms, parameters of visceral sensitivity, gene expression of elements of the epithelial barrier, and fecal protease activity. Conclusion and Inferences There was no evidence of increased infiltration or altered localization of MCs in the colonic mucosa of patients with IBS. These MC characteristics were not linked to global IBS symptoms or mucosal expression of elements of the epithelial barrier. These findings indicate that quantity and location of mucosal MCs are factors not involved in the pathophysiology of IBS.
|
|
| 26. |
- Tack, J., et al.
(författare)
-
Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts
- 2018
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:8, s. 1425-1433
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. Methods A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. Results Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism. Conclusion Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.
|
|
| 27. |
|
|
| 28. |
- Törnblom, H., et al.
(författare)
-
Gastroesofageal refluxsjukdom – gammal bekant med nya ansikten : Management of patients with gastroesophageal reflux disease can be optimized
- 2022
-
Ingår i: Läkartidningen. - 0023-7205. ; 119
-
Tidskriftsartikel (refereegranskat)abstract
- Gastroesophageal reflux disease (GERD) often requires lifelong treatment to return to and maintain a normal quality of life. Proton pump inhibitors (PPIs) offer effective medical treatment and can be used for a long time with good safety margins. The diagnostic criteria for GERD must be strictly based on current guidelines and the need for maintained treatment must be regularly evaluated. When medical treatment fails (> 20%), the patient should be offered a consultation with a specialist in the field. Too many patients who are currently treated with PPI for suspected GERD ultimately require treatment with a completely different diagnosis in focus. The investigation and treatment options are several and well-defined in the event of PPI failure in patients with well documented GERD. The indications for surgical treatment are well established, but this treatment option is likely underused today.
|
|
