| 61. |
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| 62. |
- Romanos, Jihane, et al.
(author)
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Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants
- 2014
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 63:3, s. 415-422
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Journal article (peer-reviewed)abstract
- BACKGROUND: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. OBJECTIVE: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. DESIGN: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. RESULTS: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. CONCLUSIONS: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.
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| 63. |
- Sayin, Sama I., et al.
(author)
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Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.
- 2013
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In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 17:2, s. 225-35
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Journal article (peer-reviewed)abstract
- Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.
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| 64. |
- Abdelrahman, Islam, 1982-, et al.
(author)
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Evaluation of Glandular Liposculpture as a Single Treatment for Grades I and II Gynaecomastia
- 2018
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In: Aesthetic Plastic Surgery. - : Springer. - 0364-216X .- 1432-5241. ; 42:2, s. 1222-1230
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Journal article (peer-reviewed)abstract
- BackgroundGynaecomastia is a benign enlargement of the male breast, of which the psychological burden on the patient can be considerable, with the increased risk of disorders such as depression, anxiety, and social phobia. Minimal scarring can be achieved by liposuction alone, though it is known to have a limited effect on the dense glandular and fibroconnective tissues. We know of few studies published on “liposuction alone”, so we designed this study to evaluate the outcome of combining liposuction with glandular liposculpturing through two axillary incisions as a single treatment for the management of grades I and II gynaecomastia.MethodsWe made a retrospective analysis of 18 patients with grade I or II gynaecomastia who were operated on by combined liposuction and glandular liposculpturing using a fat disruptor cannula, without glandular excision, during the period 2014–2016. Patient satisfaction was assessed using the Breast Evaluation Questionnaire (BEQ), which is a 5-point Likert scale (1 = very dissatisfied; 2 = dissatisfied; 3 = neither; 4 = satisfied; 5 = very satisfied). The post-operative aesthetic appearance of the chest was evaluated by five independent observers on a scale from 1 to 5 (5 = considerable improvement).ResultsThe patient mean (SD) overall satisfaction score was 4.7 (0.7), in which 92% of the responders were “satisfied” to “very satisfied”. The mean (SD) BEQ for all questions answered increased from 2.1 (0.2) “dissatisfied” preoperatively to 4.1 (0.2) “satisfied” post-operatively. The observers’ mean (SD) rate for the improvement in the shape of the front chest wall was 4.1 (0.7). No haematomas were recorded, one patient developed a wound infection, and two patients complained of remnants of tissue. The median (IQR) body mass index was 27.4 (26.7–29.4), 11 patients had gynaecomastia grade I, and 7 patients grade II. The median (IQR) volume of aspirated fat was 700 ml (650–800), operating time was 67 (65–75) minutes, 14 patients had general anaesthesia, and hospital charges were US$ 538 (481–594).ConclusionsCombined liposuction and liposculpturing using the fat disruptor cannula resulted in satisfied patients and acceptable outcomes according to the observers’ ratings. It could be a useful alternative with an outcome that corresponds to that of more expensive methods.
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| 65. |
- Aleman, Soo, et al.
(author)
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A Risk for Hepatocellular Carcinoma Persists Long-term After Sustained Virologic Response in Patients With Hepatitis C-Associated Liver Cirrhosis
- 2013
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 57:2, s. 230-236
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Journal article (peer-reviewed)abstract
- Background. The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. Methods. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Results. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. Conclusions. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.
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| 66. |
- Amid Hägg, Shadi, et al.
(author)
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Nocturnal gastroesophageal reflux increases the risk of daytime sleepiness in women
- 2019
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In: Sleep Medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 53, s. 94-100
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Daytime sleepiness is common in women and has negative health effects. Nocturnal gastroesophageal reflux (nGER) and snoring are risk factors for daytime sleepiness, but the effect of their interaction remains unknown. The aim of this study was to examine how nGER and snoring combined affected daytime sleepiness and involuntary falling asleep in women.METHODS: A questionnaire was sent to randomly selected women in 2000 and 2010. Participants who answered questions regarding both nGER and snoring in both questionnaires were included (N = 4882). Daytime sleepiness was defined as severe or very severe problems with daytime sleepiness. Involuntary falling asleep was defined as sometimes, often or very often falling asleep involuntarily during the day. Respondents snoring loudly and disturbingly sometimes, often or very often were defined as snorers. Having nocturnal heartburn or acid reflux sometimes, often or very often was defined as having nGER.RESULTS: Daytime sleepiness was reported by 14% of the participants, involuntary falling asleep by 11%. After adjustment for age, smoking, physical activity, caffeine intake and alcohol dependency, increased odd ratios (ORs) for both daytime sleepiness (adjusted OR 4.2, 95% confidence interval (CI): 1.9-9.2) and involuntary falling asleep (adjusted OR 3.1, 95% CI: 1.5-6.4) were seen in women with the combination of nGER and snoring at both baseline and follow-up. The association with daytime sleepiness was also strong for those with only persistent nGER but not for those with only persistent snoring.CONCLUSION: Women with nGER were at increased risk of developing daytime sleepiness and snoring augmented this association. In addition, women with both nGER and snoring were also at increased risk of developing involuntary falling asleep.
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| 67. |
- Arora, Tulika, et al.
(author)
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Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass
- 2017
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In: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 11:9, s. 2035-2046
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Journal article (peer-reviewed)abstract
- Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with shamoperated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham-and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGBversus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.
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| 68. |
- Backman, Olof, et al.
(author)
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Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels : A Nationwide Cohort Study From Sweden
- 2019
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In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 269:5, s. 895-902
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.SUMMARY OF BACKGROUND DATA: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.METHODS: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.RESULTS: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67-0.89; P < 0.001).CONCLUSIONS: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetes but also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.
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| 69. |
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| 70. |
- Block, Mattias, 1968, et al.
(author)
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Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis.
- 2016
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In: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2016
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Journal article (peer-reviewed)abstract
- Introduction. The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity. Material and Methods. Surgical whole intestinal wall colon specimens from UC patients (n = 22) and controls (n = 10) were studied. Clinical history, pharmacological treatment, and modified Mayo-score were recorded. Tissue inflammation was graded, and sections were stained with antibodies recognizing galectin-1, galectin-2, galectin-3, and galectin-4. Results. Galectin-1 was undetectable in normal and UC colonic epithelium, while galectin-2, galectin-3, and galectin-4 were strongly expressed. A tendency towards diminished epithelial expression with increased inflammatory grade for galectin-2, galectin-3, and galectin-4 was also found. In the inflammatory cells, a strong expression of galectin-2 and a weak expression of galectin-3 were seen. No clear-cut correlation between epithelial galectin expression and severity of the disease was found. Conclusion. Galectin expression in patients with UC seems to be more dependent on disease focality and individual variation than on degree of tissue inflammation.
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