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Obesity is a world-wide epidemic and it is a risk factor for type 2 diabetes (T2D). Few randomized controlled studies have compared the 2 most common surgical procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in the treatment of obese patients with T2D.To compare diabetes remission rates (glycosylated hemoglobin ≤6.0%, without diabetes medications) in obese T2D patients (body mass index, 35-50) undergoing RYGB or SG.Three University Hospital clinics and 1 Regional Hospital in Sweden.Forty-nine patients with T2D were included. Twenty-five were randomized to RYGB and 24 to SG. There was no difference between groups regarding patient characteristics, duration of T2D, overall usage of antidiabetic medications, or glycosylated hemoglobin levels. All patients (100%) completed 1-year follow-up and 47 (95.9%) 2-year follow-up.Remission of T2D was not significantly different between the RYGB and SG, reaching 44% and 46% (n = 25 and n = 24, respectively, P = .897, power = .80) at 1 year, and 48% and 55% (n = 25 and n = 22, respectively, P = .654) at 2 years of follow-up. Similarly, mean glycosylated hemoglobin was improved in both groups at 1 and 2 years, with no significant differences between the groups (RYGB baseline versus 1 yr; mean ± standard deviation: 7.9 ± 1.5 versus 5.8 ± .6%, P.0001; versus 2 yr: 5.9 ± .7%, P.0001; SG baseline versus 1 yr: 8.2 ± 1.9 versus 5.9 ± .7%, P.0001; versus 2 yr: 5.9 ± 1.1%, P .0001). Total weight loss was not different but percentage excess weight loss was higher after RYGB compared with SG both at 1 and 2 years; mean ± standard deviation: 78 ± 22 versus 60 ± 22%, and 76 ± 24 versus 54 ± 21%, respectively (P.01 for both). Waist circumference also decreased significantly more in the RYGB group.Despite superior excess weight loss after RYGB, T2D remission rates did not differ significantly between RYGB and SG after 2 years. Long-term follow-up data are needed to define the role of SG in the treatment of patients with obesity and T2D.

A promising strategy to limit cholera severity involves blockers mimicking the canonical cholera toxin ligand (CT) ganglioside GM1. However, to date the efficacies of most of these blockers have been evaluated in noncellular systems that lack ligands other than GM1. Importantly, the CT B subunit (CTB) has a noncanonical site that binds fucosylated structures, which in contrast to GM1 are highly expressed in the human intestine. Here we evaluate the capacity of norbornene polymers displaying galactose and/or fucose to block CTB binding to immobilized protein-linked glycan structures and also to primary human and murine small intestine epithelial cells (SI ECs). We show that the binding of CTB to human SI ECs is largely dependent on the noncanonical binding site, and interference with the canonical site has a limited effect while the opposite is observed with murine SI ECs. The galactose-fucose polymer blocks binding to fucosylated glycans but not to GM1. However, the preincubation of CT with the galactose-fucose polymer only partially blocks toxic effects on cultured human enteroid cells, while preincubation with GM1 completely blocks CT-mediated secretion. Our results support a model whereby the binding of fucose to the noncanonical site places CT in close proximity to scarcely expressed galactose receptors such as GM1 to enable binding via the canonical site leading to CT internalization and intoxication. Our finding also highlights the importance of complementing CTB binding studies with functional intoxication studies when assessing the efficacy inhibitors of CT.

Background/Aim A number of patients continue to suffer from chronic abdominal pain of unknown origin, which may also lead to a prolonged use of opioid analgesics. Symptoms of abdominal pain, nausea and vomiting in this patient group resemble the characteristics of the Roux stasis Syndrome. The aim was to elucidate relationships between chronic abdominal pain, Roux limb motor activity and opioid analgesics. Methods Roux limb high-resolution manometry and ratings of abdominal pain and quality of life were analysed in 15 gastric bypass patients reporting abdominal pain of unknown origin. Effect of acute opiate administration (morphine i.v.) on fasting Roux limb motor activity was assessed in asymptomatic and morphine-naive gastric bypass patients (n = 9) and compared with an untreated control group (n = 11). Results In the symptomatic patient group, we found disturbed Roux limb motor patterns in 10 out of 15 examinations, but no signs of Roux stasis syndrome. A high prevalence of prescribed opioid analgesics as well as a high number of reoperations in this group. The worst quality of life and the highest number of pain-killing medications were observed among the patients with distal pacemaker activity in Roux limb. In the morphine-naive and asymptomatic patients, morphine increased the muscular tone in the Roux limb during phase III-like motor activity. Summary and Conclusions A majority of the RYGBP patients with chronic abdominal pain had a disturbed Roux limb fasting motility, and there was a high prevalence of prescribed opioid analgesics. In opiate-naive RYGBP patients, acute morphine intravenously increased the muscular tone of the Roux limb.

Cholera toxin (CT) enters host intestinal epithelia cells, and its retrograde transport to the cytosol results in the massive loss of fluids and electrolytes associated with severe dehydration. To initiate this intoxication process, the B subunit of CT (CTB) first binds to a cell surface receptor displayed on the apical surface of the intestinal epithelia. While the mono-sialoganglioside GM1 is widely accepted to be the sole receptor for CT, intestinal epithelial cell lines also utilize fucosylated glycan epitopes on glycoproteins to facilitate cell surface binding and endocytic uptake of the toxin. Further, L-fucose can competively inhibit CTB binding to intestinal epithelia cells. Here, we use competition binding assays with L-fucose analogs to decipher the molecular determinants for L-fucose inhibition of cholera toxin subunit B (CTB) binding. Additionally, we find that mono- and di-fucosylated oligosaccharides are more potent inhibitors than L-fucose alone, with the LeY tetrasaccharide emerging as the most potent inhibitor of CTB binding to two colonic epithelial cell lines (T84 and Colo205). Finally, a non-natural fucose-containing polymer inhibits CTB binding two orders of magnitude more potently than the LeY glycan when tested against Colo205 cells. This same polymer also inhibits CTB binding to T84 cells and primary human jejunal epithelial cells in a dose-dependent manner. These findings suggest the possibility that polymeric display of fucose might be exploited as a prophylactic or therapeutic approach to block the action of CT toward the human intestinal epithelium.

The motility of the upper gut after Roux-en-Y gastric bypass (RYGBP) is underexplored. We aimed to investigate the oesophago-gastro-Roux limb motor activity during fasting and after food intake.Eighteen morbidly obese patients were examined at least 2 years after RYGBP. A high-resolution manometry catheter was positioned to straddle the oesophagogastric junction, the gastric pouch and the proximal Roux limb using transmucosal potential difference measurements. Three patients with vertical banded gastroplasty (VBG) were also studied.During the fasting state, the gastric pouch had low or no activity whereas the Roux limb exhibited regular migrating motility complexes (MMCs) being initiated just distal to gastroenteroanastomosis. Median cycle duration was 72 min, and the median propagating velocity of the phase III MMC phase was 2.7 cm/min (n = 8). When patients were asked to eat until they felt comfortably full, intraluminal pressure increased by 6 to 8 cmH₂O without any significant difference between gastric pouch and the Roux limb (n = 9). The increased intraluminal pressure following food intake correlated neither to weight loss nor to meal size or rate of eating.A successful RYGBP is associated with MMC in the Roux limb during fasting. The gastric pouch and the Roux limb behaved as a common cavity during food ingestion. Data do not support the hypothesis that the alimentary limb pressure in response to food intake influences either meal size or weight loss.

The prevalence of overweight and obesity has exploded in the post-industrial era. Life style interventions like dieting and exercise can induce a marked weight loss, but the main problem for most patients is to maintain the reduced body weight over time. Gastric bypass surgery is a commonly performed and very effective method for achieving a pronounced and sustained weight loss including metabolic improvements in obese patients. Despite the therapeutic successfulness there are known side-effects like chronic postprandial nausea and pain that in some patients become intractable. The pathophysiology is complex and partly unexplored. The physician or surgeon handling a patient with "post-bariatric symptoms" must be aware of the risk for symptom aggravations due to iatrogenic opioid-associated intestinal dysmotility. The present paper gives a brief overview of obesity surgery and its associated postsurgical conditions with a focus on the unexplored role of the Roux-limb following gastric bypass surgery.

Background The long-term results of Roux-en-Y gastric bypass (gastric bypass) and vertical banded gastroplasty (VBG) from randomized studies have not been described in detail. Methods Patients were randomized to gastric bypass or VBG. Body mass index (BMI), body composition, eating habits and gastrointestinal hormones were reviewed after 6 years. The frequency of reoperation was assessed up to 10 years after surgery. Results Sixty-six (80 per cent) of the 82 subjects randomized were assessed for weight and BMI 6 years after surgery, 30 (81 per cent) in the gastric bypass group and 36 (80 per cent) in the VBG group. Intention-to-treat analysis demonstrated greater weight loss after gastric bypass compared with VBG, 6 years after surgery: BMI reduced from 41·8 (95 per cent confidence interval 41·3 to 42·3) to 30·3 (28·6 to 32·0) kg/m2 for gastric bypass and from 42·3 (42·8 to 44·8) to 32·9 (31·3 to 34·5) kg/m2 for VBG (P = 0·036). Gastric bypass caused a larger loss of fat mass (P = 0·026) and better preservation of lean tissue (P = 0·009). Patients having a gastric bypass had greater postprandial responses to the satiety hormones glucagon-like peptide 1 and peptide YY (P = 0·003 and P = 0·004 respectively). Ghrelin levels did not differ between the groups. Patients with a gastric bypass maintained a lower intake of fat compared with those having VBG (P = 0·013). Some 89 per cent of patients who initially had VBG had undergone, or were scheduled for, conversion to gastric bypass at latest follow-up. Conclusion Gastric bypass was superior to VBG regarding weight loss, body composition, dietary composition and postprandial satiety hormone responses.

This thesis examines the readiness and perception in the regions of Gothenburg and Bremen towards future sea level rise. It does so through the theoretical lens of risk psychology / policy research and of climate science research. Results are built on some of the most recent research of these fields, as well as interviews with 14 people on the local, regional and national level in Germany and Sweden. Key findings of this thesis are that both contexts struggle to deal with the great uncertainties inherent in sea level rise. On the German North Sea coast, there is long experience with sea level variation and extensive civil institutions created to deal with storm surges, dikes and sea level rise which may partially compensate for inherent vulnerability to future sea level rise in this region. The novelty of sea level rise in Gothenburg and Sweden means that it is in the process of creating similar institutions and national-regional divisions of responsibility from scratch. The great uncertainty around the pace and extent of future sea level rise is however an obstacle which may have to be overcome before a more coherent response may be developed. Denna uppsats undersöker beredskap och uppfattningar kring framtida havsnivåhöjningar i Göteborg och Bremen. Detta görs med de teoretiska ansatserna riskpsykologi / beslutspsykologi och grundläggande klimatvetenskap. Uppsatsens resultat bygger på de senaste resultaten inom dessa fält, samt intervjuer med 14 personer på lokal, regional och nationell nivå i Tyskland och Sverige. Efter genomförd studie kan konstateras att bägge kontext har svårigheter att hantera de stora osäkerheter som havsnivåhöjningen medför. Tyska Nordsjökusten har mycket lång erfarenhet och kapabla offentliga institutioner vilka skapats för att hantera skyddsvallar, sjunkande landnivåer och stormfloder, vilket balanserar det prekära läge som området annars står inför. I Göteborg och i Sverige är havsnivåhöjning något fundamentalt nytt, vilket innebär att man nu försöker skapa liknande institutioner och ansvarsfördelning mellan nationellt och regionalt som de Bremen och Tyskland redan har. Ett hinder för detta är de stora osäkerheter som råder kring hastighet och absolut nivå på framtida havsnivåhöjningar. Dessa osäkerheter kan komma behöva reduceras innan problemet börjar hanteras på ett mer samordnat sätt.

Spak E, Bjorklund P, Helander H F, Vieth M, Olbers T, Casselbrant A, Lonroth H & Fandriks L (2010) Histopathology 57, 680–689 Changes in the mucosa of the Roux-limb after gastric bypass surgery Aims: Roux-en-Y gastric bypass surgery is the most efficient treatment of morbid obesity, but the mechanisms of action are still poorly understood. The aim of this study was to explore the Roux-limb mucosa after gastric bypass surgery, focusing upon basic morphology and inflammation. Methods and results: Jejunal mucosal samples from the Roux-limb were gathered from eight patients at time of surgery and 6–8 months postsurgery. Histological evaluation of inflammation and morphometric investigations were performed, cell proliferation was assessed using immunohistochemistry and inflammatory markers and angiotensin (Ang) II receptors were detected using Western blot. Cell proliferation increased and villous surface area decreased in the Roux-limb mucosa but no signs of active inflammation were observed after surgery. Protein analyses showed increased levels of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, myeloperoxidase (MPO) and the Ang II type 1(AT1) receptor after surgery, whereas the levels of inducible nitric oxide synthase (iNOS), nitrotyrosine and the Ang II type 2(AT2) receptor remained constant. Conclusion: These results indicate that the phenotype of the jejunal mucosa changes once exposed to undigested food and the increased microbial load in the Roux-limb after surgery.

Roux-en-Y gastric bypass surgery is the most efficient treatment of morbid obesity, but the mechanisms of action are still poorly understood. The aim of this study was to explore the Roux-limb mucosa after gastric bypass surgery, focusing upon basic morphology and inflammation.Jejunal mucosal samples from the Roux-limb were gathered from eight patients at time of surgery and 6-8 months postsurgery. Histological evaluation of inflammation and morphometric investigations were performed, cell proliferation was assessed using immunohistochemistry and inflammatory markers and angiotensin (Ang) II receptors were detected using Western blot. Cell proliferation increased and villous surface area decreased in the Roux-limb mucosa but no signs of active inflammation were observed after surgery. Protein analyses showed increased levels of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, myeloperoxidase (MPO) and the Ang II type 1(AT(1)) receptor after surgery, whereas the levels of inducible nitric oxide synthase (iNOS), nitrotyrosine and the Ang II type 2(AT(2)) receptor remained constant.These results indicate that the phenotype of the jejunal mucosa changes once exposed to undigested food and the increased microbial load in the Roux-limb after surgery.

Aims/hypothesis: In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo. Methods: Six-week-old male C57BL/6J wild-type and Adipoq −/− mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4–12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35–50 kg/m2) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry. Results: AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p