| 1. |
- Barazanji, Nawroz, et al.
(författare)
-
Irritable bowel syndrome in women: Association between decreased insular subregion volumes and gastrointestinal symptoms
- 2022
-
Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 35
-
Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC.
|
|
| 2. |
- Bednarska, Olga, et al.
(författare)
-
A postbiotic fermented oat gruel may have a beneficial effect on the colonic mucosal barrier in patients with irritable bowel syndrome
- 2022
-
Ingår i: Frontiers in Nutrition. - : FRONTIERS MEDIA SA. - 2296-861X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm (R)( ), also called Profermin (R), is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. In this study, we investigated whether ReFerm (R) has a beneficial effect on the intestinal epithelial barrier function in patients with IBS.Materials and methods: Thirty patients with moderate to severe IBS-diarrhoea (IBS-D) or IBS-mixed (IBS-M) were treated with enema containing ReFerm (R) or placebo. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of treatment with ReFerm (R) or placebo twice daily. The biopsies were mounted in Ussing chambers, and paracellular and transcellular permeabilities were measured for 120 min. In addition, the effects of ReFerm (R) or placebo on the epithelial barrier were investigated in vitro using Caco-2 cells.Results: ReFerm (R) reduced paracellular permeability (p < 0.05) and increased transepithelial resistance (TER) over time (p < 0.01), whereas the placebo had no significant effect in patients. In ReFerm (R)-treated Caco-2 cells, paracellular and transcellular permeabilities were decreased compared to the control (p < 0.05) and placebo (p < 0.01). TER was increased in Caco-2 ReFerm (R)-treated cells, and normalised TER was increased in ReFerm (R)-treated Caco-2 cells compared to control (p < 0.05) and placebo-treated (p < 0.05) cells.Conclusion: ReFerm (R) significantly reduced paracellular permeability and improved TER in colonic biopsies collected from patients with IBS and in a Caco-2 cell model. Our results offer new insights into the potential benefits of ReFerm (R) in IBS management. Further studies are needed to identify the molecular mechanisms underlying the barrier-protective properties of ReFerm (R).
|
|
| 3. |
- Biskou, Olga, et al.
(författare)
-
Increased Numbers of Enteric Glial Cells in the Peyers Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohns Disease
- 2022
-
Ingår i: Cells. - Basel, Switzerland : MDPI. - 2073-4409. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohns disease (CD) is elusive. Microscopic erosions over the ileal Peyers patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyers patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyers patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyers patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyers patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.
|
|
| 4. |
- Bonfiglio, Ferdinando, et al.
(författare)
-
GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome
- 2021
-
Ingår i: Cell Genomics. - Cambridge, MA, United States : Elsevier. - 2666-979X. ; 1:3
-
Tidskriftsartikel (refereegranskat)abstract
- Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
|
|
| 5. |
- Bureychak, Tetyana, et al.
(författare)
-
Symptoms and health experience in irritable bowel syndrome with focus on men
- 2022
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background Irritable bowel syndrome (IBS) is a disorder with a predominance in women; IBS in men is less studied. The present study evaluated symptoms as well as health and social experiences of men with IBS. Methods This cross-sectional study included 293 patients with IBS (64 men) and 363 non-IBS controls (62 men). Gastrointestinal symptom diaries were filled in prospectively, and data on comorbidities and healthcare-seeking behavior were assessed by questionnaires. Men with IBS were compared with men without IBS and women with IBS. Key results Compared with women with IBS, men with IBS had fewer contacts with the healthcare system, fewer psychiatric comorbidities, fewer sleeping problems, and less chronic pain. Urgency to defecate and nausea were less common, and stool frequency was higher in men with IBS. There was no difference between men with and without IBS in terms of educational level, satisfaction with household economy, or living with a partner. In contrast, women with IBS more often lived alone, were more often dissatisfied with household economy, and had a lower educational level than women without IBS. Men with IBS had the same proportion of full-time employment as men without IBS but in contrast, the proportion of women with IBS in full-time employment was only 34%, compared to 50% of the women without IBS. Conclusion and inferences The present study improves the understanding of mens experiences of IBS and suggests that sex and gender may be integrated into the biopsychosocial model of IBS.
|
|
| 6. |
- Casado-Bedmar, Maite, et al.
(författare)
-
Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS : A possible association with microbiota?
- 2022
-
Ingår i: Journal of Leukocyte Biology. - : Alan R. Liss Inc.. - 0741-5400 .- 1938-3673. ; 111:3, s. 655-665
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota.
|
|
| 7. |
- Fortelius, Mikael, et al.
(författare)
-
The Origin and Early History of NOW as It Happened
- 2023
-
Ingår i: Evolution of Cenozoic Land Mammal Faunas and Ecosystems: 25 years of the NOW database of fossil mammals.. - : Springer. ; , s. 7-32
-
Bokkapitel (refereegranskat)abstract
- The NOW database of fossil mammals came to be through a confluence of several initiatives spanning multiple decades. The first public version of NOW database was released in 1996 and the first Advisory Board was established the year after. Originally, NOW stood for Neogene of the Old World but with the gradual expansion of the database the acronym was eventually reassigned to stand for New and Old Worlds. The structure of what would become NOW was originally cloned from the ETE database of the Smithsonian Institution and the first NOW version accessible over the internet was a node of the ETE database. The first standalone, online version of NOW was launched in 2005 and the first formal steering group was established in 2009. During its existence, NOW has been funded, directly or indirectly, by several organizations but fundamentally it has always been an unfunded community effort, dependent on voluntary work by the participants.
|
|
| 8. |
- Gerdin, Linda, et al.
(författare)
-
Acute psychological stress increases paracellular permeability and modulates immune activity in rectal mucosa of healthy volunteers
- 2023
-
Ingår i: United European Gastroenterology journal. - : John Wiley & Sons Ltd. - 2050-6406 .- 2050-6414. ; 11:1, s. 31-41
-
Tidskriftsartikel (refereegranskat)abstract
- Background Psychological stress and increased permeability are implicated as contributing factors in the initiation and worsening of gastrointestinal diseases. A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported. Objective To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress-induced molecular events in the rectal mucosa under healthy conditions. Methods Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real-time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress. Results Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress-induced reduction in RNA expression of genes related to immune cell activation and maturation (CR2, CD20, TCLA1, BANK1, CD22, FDCSP), signaling molecules of homing of immune cells to the gut (chemokines: CCL21, CXCL13, and CCL19, and receptors: CCR7, CXCR5), and innate immunity (DUOX2). Eight of the 10 top down-regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with DUOX2 expression. Conclusion Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress-mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders.
|
|
| 9. |
- Haziot, Susanna V., et al.
(författare)
-
Traveling Water Waves - The Ebb and Flow of Two Centuries
- 2022
-
Ingår i: Quarterly of Applied Mathematics. - : American Mathematical Society (AMS). - 0033-569X .- 1552-4485. ; 80:2, s. 317-401
-
Tidskriftsartikel (refereegranskat)abstract
- This survey covers the mathematical theory of steady water waves with an emphasis on topics that are at the forefront of current research. These areas include: variational characterizations of traveling water waves; analytical and numerical studies of periodic waves with critical layers that may overhang; existence, nonexistence, and qualitative theory of solitary waves and fronts; traveling waves with localized vorticity or density stratification; and waves in three dimensions.
|
|
| 10. |
- Ingemansson, Anna, et al.
(författare)
-
Defecation Symptoms in Relation to Stool Consistency Significantly Reflect the Dyssynergic Pattern in High-resolution Anorectal Manometry in Constipated Patients
- 2024
-
Ingår i: Journal of Clinical Gastroenterology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0192-0790 .- 1539-2031. ; 58:1, s. 57-63
-
Tidskriftsartikel (refereegranskat)abstract
- Goals: To evaluate the usefulness of a 2-week patient-completed bowel habit and symptom diary as a screening tool for disordered rectoanal coordination (DRC).Background: DRC is an important subgroup of chronic constipation that benefits from biofeedback treatment. Diagnosis of DRC requires a dyssynergic pattern (DP) of attempted defecation in high-resolution anorectal manometry (HRAM) and at least 1 other positive standardized examination, such as the balloon expulsion test or defecography. However, HRAM is generally limited to tertiary gastroenterology centres and finding tools for selecting patients for referral for further investigations would be of clinical value.Study: Retrospective data from HRAM and a 2-week patient-completed bowel habit and symptom diary from 99 chronically constipated patients were analyzed.Results: Fifty-seven percent of the patients had a DP pattern during HRAM. In the DP group, 76% of bowel movements with loose or normal stool resulted in a sense of incomplete evacuation compared with 55% of the non-DP group (P=0.004). Straining and sensation of incomplete evacuation with the loose stool were significantly more common in the DP group (P=0.032). Hard stool was a discriminator for non-DP (P=0.044). Multiple logistic regression including incomplete evacuation and normal stool predicted DP with a sensitivity of 82% and a specificity of 50%.Conclusions: The sensation of incomplete evacuation with loose or normal stool could be a potential discriminator in favor of DP in chronically constipated patients. The bowel habit and symptom diary may be a useful tool for stratifying constipated patients for further investigation of suspected DRC.
|
|
| 11. |
- Jones, Michael P., et al.
(författare)
-
Clusters of community-dwelling individuals empirically derived from stool diaries correspond with clinically meaningful outcomes
- 2021
-
Ingår i: European Journal of Gastroenterology and Hepathology. - : Lippincott Williams & Wilkins. - 0954-691X .- 1473-5687. ; 33:1S, s. e740-e745
-
Tidskriftsartikel (refereegranskat)abstract
- Background Functional gastrointestinal disorders (FGIDs) are diagnosed according to expert consensus criteria based on recall of symptoms over periods of 3 months or longer. Whether the expert opinion concords with underlying disease process and whether individual recall is accurate are both in doubt. This study aimed to identify naturally occurring clusters of individuals with respect to symptom pattern, evaluate their significance, compare cluster profiles with expert opinion and evaluate their temporal stability.Methods As part of a random population study of FGID-related symptoms, we first explored the use of prospective stool and symptom diaries combined with empirical grouping of individuals into clusters using nonhierarchical cluster analysis.Results The analysis identified two clusters of individuals, one of which was characterized by elevated scores on all domains of symptoms (26% of the sample) and one that was low to average on all domains (74% of the sample). Cluster membership was found to be stable over a long interval. Clusters were found to differ on most domains of quality-of-life (d = 0.46–0.74), self-rated health (d = −0.42) and depression (d = −0.42) but not anxiety. Prevalence of clinically diagnosed irritable bowel syndrome (IBS) was higher in the more impacted cluster (33%) compared with the healthy cluster (13%; P < 0.0001).Conclusion A naturalistic classification of individuals challenges consensus criteria in showing that some IBS individuals have a symptom experience not unlike health. The proposed approach has demonstrated temporal stability over time, unlike consensus criteria. A naturalistic disease classification system may have practical advantages over consensus criteria when supported by a decision-analytic system.
|
|
| 12. |
- Jönsson, Daniel, et al.
(författare)
-
VisualNeuro : A Hypothesis Formation and Reasoning Application for Multi-Variate Brain Cohort Study Data
- 2020
-
Ingår i: Computer graphics forum (Print). - : Wiley-Blackwell Publishing Inc.. - 0167-7055 .- 1467-8659. ; 39:6, s. 392-407
-
Tidskriftsartikel (refereegranskat)abstract
- We present an application, and its development process, for interactive visual analysis of brain imaging data and clinical measurements. The application targets neuroscientists interested in understanding the correlations between active brain regions and physiological or psychological factors. The application has been developed in a participatory design process and has subsequently been released as the free software VisualNeuro. From initial observations of the neuroscientists workflow, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration requiring the use of many tools side by side. Consequently, our application has been designed to simplify the workflow combining statistical analysis with interactive visual exploration. The resulting environment comprises parallel coordinates for effective overview and selection, Welchs t-test to filter out brain regions with statistically significant differences and multiple visualizations for comparison between brain regions and clinical parameters. These exploration concepts enable neuroscientists to interactively explore the complex bidirectional interplay between clinical and brain measurements and easily compare different patient groups. A qualitative user study has been performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights and is an effective tool for hypothesis formation.
|
|
| 13. |
- Katinios, Georgios, et al.
(författare)
-
Increased Colonic Epithelial Permeability and Mucosal Eosinophilia in Ulcerative Colitis in Remission Compared With Irritable Bowel Syndrome and Health
- 2020
-
Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1078-0998 .- 1536-4844. ; 26:7, s. 974-984
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundBarrier dysfunction is recognized as a pathogenic factor in ulcerative colitis (UC) and irritable bowel syndrome (IBS), but it is unclear to what extent the factors related to barrier dysfunction are disease-specific. The aim of this study was to compare these aspects in UC patients in remission, IBS patients, and healthy controls (HCs).MethodsColonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed, and 15 HCs. Ulcerative colitis patients had recently been treated for relapse, and biopsies were taken from earlier inflamed areas. Biopsies were mounted in Ussing chambers for measurements of intestinal paracellular permeability to 51chromium (Cr)-ethylenediaminetetraacetic acid (EDTA). In addition, biopsies were analyzed for mast cells and eosinophils by histological procedures, and plasma tumor necrosis factor (TNF)-α was assessed by ELISA.ResultsUssing chamber experiments revealed an increased 51Cr-EDTA permeability in UC and IBS (P < 0.05). The 51Cr-EDTA permeability was higher in UC compared with IBS (P < 0.005). There were increased numbers of mucosal mast cells and eosinophils in UC and IBS and more eosinophils in UC compared with IBS (P < 0.05). Also, increased extracellular granule content was found in UC compared with HCs (P < 0.05). The 51Cr-EDTA permeability correlated significantly with eosinophils in all groups. Plasma TNF-α concentration was higher in UC compared with IBS and HCs (P < 0.0005).ConclusionsResults indicate a more permeable intestinal epithelium in inactive UC and IBS compared with HCs. Ulcerative colitis patients, even during remission, demonstrate a leakier barrier compared with IBS. Both eosinophil numbers and activation state might be involved in the increased barrier function seen in UC patients in remission.
|
|
| 14. |
- Kremer, Christine, et al.
(författare)
-
European Stroke Organisation guidelines on stroke in women : Management of menopause, pregnancy and postpartum
- 2022
-
Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- Pregnancy, postpartum and menopause are regarded as periods women are more vulnerable to ischaemic events. There are conflicting results regarding stroke risk and hormone replacement therapy (HRT) during menopause. Stroke in pregnancy is generally increasing with serious consequences for mother and child; therefore, recommendations for acute treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) are needed. The aim of this guideline is to support and guide clinicians in treatment decisions in stroke in women. Following the “Grading of Recommendations and Assessment, Development and Evaluation (GRADE)” approach, the guidelines were developed according to the European Stroke Organisation (ESO) Standard Operating Procedure. Systematic reviews and metanalyses were performed. Based on available evidence, recommendations were provided. Where there was a lack of evidence, an expert consensus statement was given. Low quality of evidence was found to suggest against the use of HRT to reduce the risk of stroke (ischaemic and haemorrhagic) in postmenopausal women. No data was available on the outcome of women with stroke when treated with HRT. No sufficient evidence was found to provide recommendations for treatment with IVT or MT during pregnancy, postpartum and menstruation. The majority of members suggested that pregnant women can be treated with IVT after assessing the benefit/risk profile on an individual basis, all members suggested treatment with IVT during postpartum and menstruation. All members suggested treatment with MT during pregnancy. The guidelines highlight the need to identify evidence for stroke prevention and acute treatment in women in more vulnerable periods of their lifetime to generate reliable data for future guidelines.
|
|
| 15. |
- Kurilshikov, Alexander, et al.
(författare)
-
Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
-
Tidskriftsartikel (refereegranskat)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
|
|
| 16. |
- Mathus-Vliegen, Elisabeth, et al.
(författare)
-
Weight loss with or without intragastric balloon causes divergent effects on ghrelin cell expression
- 2021
-
Ingår i: Obesity Science & Practice. - : Wiley-Blackwell Publishing Inc.. - 2055-2238. ; 7:2, s. 199-207
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The mechanism of action of intragastric balloons in the treatment of obesity is not fully understood. One of the hypotheses is that balloons might have an effect on the fundus, the area of ghrelin production. Methods: Participants were randomized to a 13-week period of sham or balloon treatment followed by a 13-week period of balloon therapy in everyone. Blood samples for ghrelin levels were taken in the fasting state and after a breakfast at the start, after 13 and 26 weeks. Biopsies for ghrelin cell immunohistochemistry were taken from the fundus at endoscopy. Results: Seven participants entered the balloon-balloon (BB) group and 11 the sham-balloon (SB) group. Despite a considerable weight loss, a median -17.9 kg (interquartile ranges -23.8 to -0.5) in the BB group and -18.3 kg (-22.7 to -14.7) in the SB group, fasting ghrelin and meal-induced ghrelin response did not change. In the SB group, the number of ghrelin cells increased significantly (p 0.001) from 110.6 (83.6-118.9) to 160.2 (128.5-223.0) while on sham treatment and returned to initial levels, 116.3 (91.7-146.9) (p 0.001), when they received their first balloon. No significant changes in ghrelin cell numbers were observed in the BB group. Conclusion: In participants without a balloon, weight loss induced an increase in ghrelin cell numbers in the fundus, which was annulled by the subsequent placement of a balloon. The effect of a balloon might be explained by effects on ghrelin cell numbers or ghrelin cell activity.
|
|
| 17. |
- Meira de-Faria, Felipe, 1984-, et al.
(författare)
-
Altered interaction between enteric glial cells and mast cells in the colon of women with irritable bowel syndrome
- 2021
-
Ingår i: Neurogastroenterology and Motility. - : Blackwell Science Ltd.. - 1350-1925 .- 1365-2982. ; 33:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Enteric glial cells (EGC) and mast cells (MC) are intimately associated with gastrointestinal physiological functions. We aimed to investigate EGC-MC interaction in irritable bowel syndrome (IBS), a gut-brain disorder linked to increased intestinal permeability, and MC.Methods: Parallel approaches were used to quantify EGC markers in colonic biopsies from healthy controls (HC) and patients with IBS. Data were correlated with MC, vasoactive intestinal polypeptide (VIP) and VIP receptors (VPAC1/VPAC2) expressions, and bacterial translocation through biopsies mounted in Ussing chambers. In addition, we investigated the effects of EGC mediators on colonic permeability and the pharmacological-induced responses of EGC and MC cell lines.Key Results: Immunofluorescence of IBS colonic mucosa, as well as Western blotting and ELISA of IBS biopsy lysates, revealed increased glial fibrillary intermediate filament (GFAP) expression, indicating EGC activation. Mucosal GFAP correlated with increased MC and VPAC1(+)MC numbers and decreased VIP+MC, which seemed to control bacterial translocation in HC. In the contrary, EGC activation in IBS correlated with less MC and VPAC1(+) MC numbers, and more VIP+ MC. In vitro, MC and EGC cell lines showed intracellular calcium responses to each other's mediators. Furthermore, EGC mediators prevented VIP-induced MC degranulation, while MC mediators induced a reactive EGC phenotype. In Ussing chambers, EGC mediators decreased paracellular passage through healthy colonic biopsies.Conclusions & Inferences: Findings suggest the involvement of EGC and MC in the control of barrier function in the human colon and indicate a potential EGC-MC interaction that seems altered in IBS, with detrimental consequences to colonic permeability. Altogether, results suggest that imbalanced EGC-MC communication contributes to the pathophysiology of IBS.
|
|
| 18. |
- Meira de Faria, Felipe, et al.
(författare)
-
Colonic paracellular permeability and circulating zonulin-related proteins
- 2021
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:4, s. 424-431
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Irritable bowel syndrome (IBS) is a gut-brain disorder associated with increased gut permeability. Zonulin has been suggested to regulate the gut barrier and claimed to be pre-haptoglobin 2 (pre-HP2) and circulating zonulin is often used as a proxy for gastrointestinal permeability. This study investigated the correlation between colonic paracellular permeability and levels of circulating zonulin and pre-HP2. Materials and Methods Colonic biopsies from 32 patients with IBS and 15 healthy controls (HC) were used to measure permeability in Ussing chambers and levels of zonulin (Cusabio ELISA). Zonulin was also measured in blood samples from 40 HC, 78 patients with IBS and 20 patients with celiac disease (CeD), before and after a gluten-free diet. In addition, we verified HP genotype and circulating pre-HP2 using a monoclonal pre-HP2 antibody (Bio-Rad) by ELISA. Results Increased colonic paracellular permeability correlated positively with zonulin levels in IBS biopsies, but negatively with plasma zonulin. We found no agreement between circulating zonulin and pre-HP2. Genotyping revealed non-specificity of the zonulin kit, as all pre-HP2 non-producers presented detectable levels. Patients with CeD displayed higher pre-HP2 and zonulin levels compared to HC. A gluten-free diet in patients with CeD led to lower serum zonulin and pre-HP2 concentrations. Conclusions Our study suggests that neither circulating zonulin nor pre-HP2 mirror colonic permeability. Our data corroborate previous reports showing the inability of the Cusabio zonulin kit to target zonulin and highlights that the results of studies using this kit must be re-examined with caution.
|
|
| 19. |
- Middha, Pooja K., et al.
(författare)
-
A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
-
Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
|
|
| 20. |
- Norlin, Anna-Karin, 1977-
(författare)
-
Exploring the Biopsychosocial Model in Irritable Bowel Syndrome : with emphasis on stress, comorbidities and fatigue
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIrritable bowel syndrome (IBS) is a common, chronic, relapsing, and sometimes disabling, symptombased disorder of gut brain interactions. It has got a female predominance and occurs in all ages, with a slight decrease among elderly. The IBS symptoms can affect everyday work and social life in addition to an increased use of health care resources. Most IBS patients are diagnosed and helped in primary health care (PHC). For many patients, available treatment is insufficient. It is known that both extraintestinal symptoms such as fatigue, as well as comorbidities such as mood disorders, chronic pain syndromes, and insomnia contribute to the illness burden, often to a larger extent than the gastrointestinal symptoms as such.Even though the pathophysiology of IBS is not completely known, it is now conceptualized as a disorder of altered brain-gut interactions, where a biopsychosocial model helps in understanding the symptoms. Exposure to stress is thought to play an important role overall in the pathology of IBS, as well as immune activation at least in a subgroup of patients.This thesis aimed to gain deeper understanding of the biopsychosocial mechanisms of IBS and its associations with stress, comorbidities, and fatigue.Methods Study I and II are based on the Twin cities IBS study population, which included IBS patients and a control group of other patients without gastrointestinal complaints from ten PHC centres in the county of Östergötland. Alongside demographics, psychosocial questionnaires and a GI symptom diary, it included analyses of hair cortisol concentrations (HCC) evaluated in study I, and data on self-rated health as well as diagnoses of comorbidities, and number of health care contacts from a regional registry, evaluated for study II.Study III of this thesis is based on the Brain-Gut study with a population of secondary care IBS patients, and healthy controls (HC). It included self-rated measures of fatigue impact on the daily life and early adverse life events, as well as measures of circulating TNF-α, and analyses of resting-state functional magnetic resonance imaging of brain areas within a mesocorticolimbic circuitry of known relevance for fatigue.Results Study I: Perceived stress was higher in the IBS group while a considerable portion of IBS patients had low levels of HCC. No association between perceived stress and HCC was seen in either group.Study II: IBS patients had lower self-rated health and more PHC utilization than the non-IBS patients. Good self-rated health was independently associated with younger age, higher sense of coherence and less gastrointestinal pain in both groups. In IBS, PHC utilization was associated with comorbidities in general, and sleep disorders in particular.Study III: Fatigue impact on daily life, and TNF- α were higher in IBS patients than in HC. In IBS, further an association was seen between fatigue impact on the one hand, and TNF- α, emotional abuse in childhood, as well as altered mesocorticolimbic connectivity on the other.Conclusion In conclusion this thesis firstly emphasizes that IBS patients in many ways, including health outcomes, consists a vulnerable group of PHC patients. We add evidence for a possible suppression of the stress response system in a substantial portion of IBS patients.Further, comorbid sleep disorders seem to be particularly associated with excess PHC utilization in IBS and could possibly be a target for treatment interventions. Moreover, alongside treating gastrointestinal pain, efforts to improve the individuals’ sense of coherence could be one way to achieve better self-rated health in both IBS and non-IBS patients.Finally, we suggest that fatigue in IBS is associated with immune activation, central alterations and to some extend also previous childhood trauma.
|
|
| 21. |
- Norlin, Anna-Karin, 1977-, et al.
(författare)
-
Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity
- 2021
-
Ingår i: Brain, behavior, and immunity. - Amsterdam, Netherlands : Elsevier. - 0889-1591 .- 1090-2139. ; 92, s. 211-220
-
Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a symptom-based disorder of gut-brain interactions generating abdominal pain. It is also associated with a vulnerability to develop extraintestinal symptoms, with fatigue often reported as one of the most disturbing. Fatigue is related to brain function and inflammation in several disorders, however, the mechanisms of such relations in IBS remain elusive. This study aimed to elucidate fatigue and its association with a resting state network of mesocorticolimbic regions of known importance in fatigue, and to explore the possible role of circulating TNF-α levels in IBS and healthy controls (HC). Resting state functional magnetic resonance imaging (fMRI) was conducted in 88 IBS patients and 47 HC of similar age and gender to investigate functional connectivity between mesocorticolimbic regions. Further, fatigue impact on daily life and plasma levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α), of known relevance to immune activation in IBS, were also measured. The selected mesocorticolimbic regions indeed formed a functionally connected network in all participants. The nucleus accumbens (NAc), in particular, exhibited functional connectivity to all other regions of interest. In IBS, fatigue impact on daily life was negatively correlated with the connectivity between NAc and dorsolateral prefrontal cortex bilaterally (left p = 0.019; right p = 0.038, corrected for multiple comparisons), while in HC, fatigue impact on daily life was positively correlated to the connectivity between the right NAc and anterior middle insula in both hemispheres (left p = 0.009; right p = 0.011). We found significantly higher levels of TNF-α in IBS patients compared to HC (p = 0.001) as well as a positive correlation between TNF-α and fatigue impact on daily life in IBS patients (rho = 0.25, p = 0.02) but not in HC (rho = −0.13, p = 0.37). There was no association between functional connectivity in the mesocorticolimbic network and plasma levels of TNF-α in either group In summary, this novel multimodal study provides the first evidence that the vulnerability to fatigue in IBS is associated with connectivity within a mesocorticolimbic network as well as immune activation. These findings warrant further investigation, both peripherally and potentially with measurements of central immune activation as well.
|
|
| 22. |
- Psarias, Theodoros, et al.
(författare)
-
Anorectal function and symptoms 6 months after robot-assisted laparoscopic radical prostatectomy: a single-center study
- 2024
-
Ingår i: Scandinavian journal of urology. - : Medical Journal Sweden AB. - 2168-1805 .- 2168-1813. ; 59, s. 104-108
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Robot-assisted laparoscopic radical prostatectomy (RALP) is a common procedure for the treatment of localised prostate cancer. Anorectal symptoms such as fecal incontinence (FI), rectal urgency or disturbed defecation have been reported after the operation. Anorectal function is dependent on the integrity of anal and pelvic nerves and muscles, rectal sensory function as well as rectal reservoir function. The aim of this study was to investigate the potential influence of RALP on anorectal physiological function and bowel symptoms.<br /> Materials and Methods: In this pilot study, 29 patients with localised prostate cancer scheduled for RALP were included. Anorectal physiology was used to measure rectal sensitivity and reservoir function as well as anal sphincter pressures. Bowel symptoms were measured by a bowel function questionnaire and a 2-week bowel function diary. Measurements were done before the operation and repeated at 6 months after the operation.<br /> Results: The study observed a significant postoperative increase in rectal sensory threshold for rectal balloon distention, from 20 to 40 mmHg, P < 0.001. This change is indicative of a decrease in rectal sensation after RALP. There were no other statistical significant differences in any of the physiological tests performed. Importantly, there was no change in any of the bowel symptoms after surgery.<br /> Conclusion: This study showed that RALP may lead to impaired rectal sensory function. This finding did not, however, seem to have any influence on the patients<acute accent> postoperative clinical bowel function.
|
|
| 23. |
- Schoemaker, Minouk J., et al.
(författare)
-
Adult weight change and premenopausal breast cancer risk : A prospective pooled analysis of data from 628,463 women
- 2020
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 147:5, s. 1306-1314
-
Tidskriftsartikel (refereegranskat)abstract
- Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
|
|
| 24. |
- Simon, Rozalyn, 1979-, et al.
(författare)
-
Magnetotactic bacteria from the human gut microbiome associated with orientation and navigation regions of the brain
- 2021
-
Ingår i: Journal of Oceanology and Limnology. - : Springer Nature. - 2096-5508 .- 2523-3521. ; 39:6, s. 2044-2052
-
Tidskriftsartikel (refereegranskat)abstract
- Magnetotactic bacteria (MTB), ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals. MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields. Similar magnetite deposits have been found throughout the tissues of the human brain, including brain regions associated with orientation such as the cerebellum and hippocampus, the origins of which remain unknown. Speculation over the role and source of MTB in humans, as well as any association with the brain, remain unanswered. We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions. We identified seven MTB in the human gut microbiome: Magnetococcus marinus, Magnetospira sp. QH-2, Magnetospirillum magneticum, Magnetospirillum sp. ME-1, Magnetospirillum sp. XM-1, Magnetospirillum gryphiswaldense, and Desulfovibrio magneticus. Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus (adjusted for total intracranial volume, uncorrected P<0.05). These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation. These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans. Further studies will be necessary to validate and elucidate the relationship between these bacteria, magnetite concentrations, and brain function.
|
|
| 25. |
- Simon, Rozalyn, et al.
(författare)
-
Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females
- 2021
-
Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood-brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r=- 0.44, p=0.002) and depression (r=- 0.50, p=0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t((33))=3.1, p(FDR)=0.02) and right lateral orbitofrontal cortex (OFC; t((33))=2.9, p(FDR)=0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r=0.28, p=0.007) and left lateral OFC (r=0.29, p=0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.
|
|
