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Trimethylamine-N-oxide (TMAO), a microbiome-derived metabolite from the metabolism of choline, betaine, and carnitines, is associated to adverse cardiovascular outcomes. A method suitable for routine quantification of TMAO and its precursors (trimethylamine (TMA), choline, betaine, creatinine, and propionyl-, acetyl-, and l-carnitine) in clinical and food samples has been developed based on LC-MS. TMA was successfully derivatized using iodoacetonitrile, and no cross-reactions with TMAO or the other methylamines were detected. Extraction from clinical samples (plasma and urine) was performed after protein precipitation using acetonitrile:methanol. For food samples (meatballs and eggs), water extraction was shown to be sufficient, but acid hydrolysis was required to release bound choline before extraction. Baseline separation of the methylamines was achieved using a neutral HILIC column and a mobile phase consisting of 25 mmol/L ammonium formate in water:ACN (30:70). Quantification was performed by MS using external calibration and isotopic labelled internal standards. The assay proved suitable for both clinical and food samples and was linear from ≈ 0.1 up to 200 μmol/L for all methylamines except for TMA and TMAO, which were linear up to 100 μmol/L. Recoveries were 91–107% in clinical samples and 76–98% in food samples. The interday (n=8, four duplicate analysis) CVs were below 9% for all metabolites in clinical and food samples. The method was applied successfully to determine the methylamine concentrations in plasma and urine from the subjects participating in an intervention trial (n=10) to determine the effect of animal food ingestion on methylamine concentrations. Graphical abstract

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It has not been clarified whether the anti-atherosclerotic effect of lingonberry can be ascribed to its content of flavonoids or dietary fibre or both. The aim of this study was to evaluate the metabolic effects of whole lingonberries compared with isolated flavonoid and fibre fractions on atherosclerotic plaques, plasma lipid profiles, gut microbiota and microbiota-dependent metabolites in an Apoe–/– mouse model. Mice fed whole lingonberries showed the lowest amount of atherosclerotic plaques, while mice fed the fibre fraction had the highest formation of caecal butyric acid. Flavonoids, rather than dietary fibre, were suggested to be the components that favour proliferation of Akkermansia, as judged by the lowest abundance of this bacterium in mice fed the fibre fraction. All groups fed lingonberry diets had both, lower Firmicutes/Bacteroidetes ratios and creatinine concentrations, compared with the control. To conclude, different components in lingonberries are associated with different physiological effects in Apoe–/– mice.

Background Support from significant others is important for participation in everyday life for persons with rheumatoid arthritis (RA). Meanwhile, significant others also experience limitations. Aims To explore how support is expressed by persons with RA and significant others, and how support relates to participation in everyday life of persons with RA. Material and methods Sixteen persons with RA and their significant others participated in individual semi-structured interviews. The material was analyzed using dyadic analysis. Results Persons with RA and significant others reported that RA and support had become natural parts of everyday life, especially emotional support. The reciprocal dynamics of support were also expressed as imperative. Also, support from people outside of the dyads and well-functioning communication facilitated everyday life. Conclusions Significant others and the support they give are prominent factors and facilitators in everyday life of persons with RA. Concurrently, the support persons with RA provide is important, along with support from outside of the dyads. Significance The results indicate that the interaction between persons with RA and the social environment is central to gain insight into how support should be provided for optimal participation in everyday life. Significant others can preferably be more involved in the rehabilitation process. Funding Agencies|Swedish Rheumatism Association under Stig Thunes Fund [20181001, ST201905]; Region Ostergotland [LIO-921841, LIO-938209]; Swedish Association of Occupational Therapists

Background and Aim Microbial contamination of the abdominal cavity is a serious concern during transgastric endoscopic interventions and perforations, particularly in patients who have inhibited gastric acid secretion due to treatment with proton pump inhibitors (PPIs). The aim of this study was to investigate the gastric and duodenal bacterial flora in patients with and without PPI treatment. Methods Patients referred for gastroscopy, without recent antibiotic treatment, were eligible for inclusion. Use of PPIs was recorded. Samples for bacterial culturing were obtained from the antrum of the stomach and from the duodenal bulb through a gastroscope. Positive cultures were examined for bacterial types and subtypes. Biopsies were taken in the antrum for urease test to detect Helicobacter pylori. Results Bacterial cultures from the stomach were obtained from 103 patients, and duodenal samples were also cultured from 49 of them, for a total of 53 patients with PPI use and 50 patients without. Positive gastric cultures were found in 42 of 53 patients with PPI use and in 13 of 50 without (P, Bacterial cultures from the stomach were obtained from 103 patients admitted for routine gastroscopy; 53 patients had ongoing proton pump inhibitor (PPI) treatment. Positive cultures were significantly more common in patients with PPI (P

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.Materials and methods: During 2016-2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing HEV infection.

Purpose: To describe the meaning of significant others in relation to participation in everyday life of persons with early diagnosed rheumatoid arthritis (RA).Materials and methods: Fifty-nine persons participated in this interview study. Inclusion criteria were three years' experience of diagnosis and being of working age. Semi-structured interviews were conducted using critical incident technique (CIT), and the material was analysed using content analysis.Results: Four categories were revealed: (1) My early RA causes activity adaptations for us all, referring to the person and significant others modifying activities. (2) Making the significant others balance between shortfalls and participation, where the participants distinguished between needing help and feeling involved in activities. (3) Physical interactions with significant others, referring to both the problematic and manageable impact RA could have on body contact. (4) Emotions in relation to activities with others, where participants described feelings of failing others, and anxiety about future activities.Conclusions: For persons with early diagnosed RA, significant others can be both hindering and facilitating for participation in everyday life. As a clinical implication, it is valuable to identify how significant others can be involved in the rehabilitation process, to enhance participation in everyday life early in the disease process.Implications for rehabilitationSignificant others of persons with rheumatoid arthritis can facilitate as well as hinder participation in everyday life, even early in the disease process.It is important to include the significant others in the rehabilitation process of persons with early diagnosed rheumatoid arthritis.It is of great importance to identify when and how significant others can be facilitators of participation in everyday life for persons with early rheumatoid arthritis.To make it easier for significant others to facilitate participation, there is a need for the healthcare system to explore ways to support significant others with easily accessible information about early rheumatoid arthritis.

I am a senior analyst at the Swedish Research Council and have more than 20 years' experience in the field of evaluation from positions at different Swedish government agencies. I have also been a politician at municipal and regional level for 5 years. In my reflection on the article "Democratic values in evaluation systems – a circle that can be squared?", I will focus on the model for systematic quality work that is described in the article, the similarities with other concepts for implementing evaluation systems, and the challenges of limiting the scope of the evaluations to be defined within the system.

Objective: The aim of this study was to analyse how support from significant others affects the associations between disease-related variables and sickness absence during the first 2 years after rheumatoid arthritis (RA) diagnosis. Method: Data from 274 people with RA (73% women) of working age (18-63 years) were retrieved from the Swedish early RA cohort TIRA-2. These data concerned disease-related variables (disease activity, activity limitations, pain intensity, and grip force), sickness absence, and perceived support from significant others. Associations of disease-related variables with sickness absence and how these associations were moderated by support from significant others were analysed using zero-inflated negative binomial regression. Results: During the 2 years after diagnosis, higher disease activity was significantly associated with increased odds of sickness absence, a connection strengthened by perceived support from family during the first year. More perceived support was also directly and significantly associated with increased odds of sickness absence during the first year. Conclusions: Support from significant others is related to sickness absence in RA, specifically during the first year after diagnosis. Although patients report high levels of support from significant others, this does not necessarily lead to more positive work outcomes. Therefore, it is important to consider other aspects of support that might influence work outcomes, e.g. type and quality of support. Future research should investigate these forms of support, and when significant others should be encouraged to support in the rehabilitation process to increase the chances of people with RA having a well-functioning and sustainable work life.

There is a growing demand for alternative protein‐source ingredients from domestically cultivated pulses in Europe, including Sweden. However, the use of legumes as a food ingredient is limited by the presence of a distinct beany flavor. Mapping the volatile compounds composition in a standardized approach will aid in comparing different legume varieties and processing treatments. The composition of volatile compounds in flour from yellow and gray peas (raw and boiled) was investigated and compared. Volatile compounds were isolated by headspace solid‐phase microextraction (HS‐SPME) and analyzed using gas chromatography‐mass spectrophotometry (GC‐MS). A total of 43 volatiles were identified, consisting mostly of aldehydes, followed by alkanes, alcohols, ketones, alkenes, furans, terpenes, aromatics, and sulfur‐containing compounds. Boiling led to a marked reduction in alcohols and an increase in aldehydes. Several markers of beany flavor, such as 1‐octen‐3‐ol, 2‐pentylfuran, and 3,5‐octadien‐2‐one, were significantly decreased after boiling. The composition of volatiles collected from yellow and gray peas was comparable, but boiled yellow pea had a higher abundance of beany flavor as compared to gray pea. Gray pea is an interesting variety to be explored further as a potential alternative to the well‐known yellow pea.

Background Perforated peptic ulcer is a life-threatening condition. Traditional treatment is surgery. Esophageal perforations and anastomotic leakages can be treated with endoscopically placed covered stents and drainage. We have treated selected patients with a perforated duodenal ulcer with a partially covered stent. The aim of this study was to compare surgery with stent treatment for perforated duodenal ulcers in a multicenter randomized controlled trial. Methods All patients presenting at the ER with abdominal pain, clinical signs of an upper G-I perforation, and free air on CT were approached for inclusion and randomized between surgical closure and stent treatment. Age, ASA score, operation time, complications, and hospital stay were recorded. Laparoscopy was performed in all patients to establish diagnosis. Surgical closure was performed using open or laparoscopic techniques. For stent treatment, a per-operative gastroscopy was performed and a partially covered stent was placed through the scope. Abdominal lavage was performed in all patients, and a drain was placed. All patients received antibiotics and intravenous PPI. Stents were endoscopically removed after 2–3 weeks. Complications were recorded and classified according to Clavien-Dindo (C-D). Results 43 patients were included, 28 had a verified perforated duodenal ulcer, 15 were randomized to surgery, and 13 to stent. Median age was 77.5 years (23–91) with no difference between groups. ASA score was unevenly distributed between the groups (p = 0.069). Operation time was significantly shorter in the stent group, 68 min (48–107) versus 92 min (68–154) (p = 0.001). Stents were removed after a median of 21 days (11–37 days) without complications. Six patients in the surgical group had a complication and seven patients in the stent group (C-D 2–5) (n.s.). Conclusions Stent treatment together with laparoscopic lavage and drainage offers a safe alternative to traditional surgical closure in perforated duodenal ulcer. A larger sample size would be necessary to show non-inferiority regarding stent treatment.

Ligand‐based NMR techniques to study protein–ligand interactions are potent tools in drug design. Saturation transfer difference (STD) NMR spectroscopy stands out as one of the most versatile techniques, allowing screening of fragments libraries and providing structural information on binding modes. Recently, it has been shown that a multi‐frequency STD NMR approach, differential epitope mapping (DEEP)‐STD NMR, can provide additional information on the orientation of small ligands within the binding pocket. Here, the approach is extended to a so‐called DEEP‐STD NMR fingerprinting technique to explore the binding subsites of cholera toxin subunit B (CTB). To that aim, the synthesis of a set of new ligands is presented, which have been subject to a thorough study of their interactions with CTB by weak affinity chromatography (WAC) and NMR spectroscopy. Remarkably, the combination of DEEP‐STD NMR fingerprinting and Hamiltonian replica exchange molecular dynamics has proved to be an excellent approach to explore the geometry, flexibility, and ligand occupancy of multi‐subsite binding pockets. In the particular case of CTB, it allowed the existence of a hitherto unknown binding subsite adjacent to the GM1 binding pocket to be revealed, paving the way to the design of novel leads for inhibition of this relevant toxin., Fingerprinting: A powerful protocol by using NMR spectroscopy and molecular dynamics to study multi‐subsite binding pockets has been developed. For cholera toxin subunit B (CTB), the combination of differential epitope mapping saturation transfer difference (DEEP‐STD) NMR, STD competition experiments, transfer‐NOESY, and Hamiltonian replica exchange molecular dynamics (HREMD) unveiled the presence of a novel subsite adjacent to the known subsites of GM1 on CTB.

Given the fast development of the field of AML Regulation, this Article aims to answer the following questions: First, how is money laundering dealt with and regulated on the EU level? Second, to which legal concerns do the chosen regulatory strategy give rise? Accordingly, this Article provides an overview of the various regulatory strategies in the global and EU regional AML Regime while at the same time points out some of the most pressing legal concerns in AML Regulation. These include the blurred line between administrative and criminal law measures and the protection of individual rights and fundamental freedoms including data protection and privacy issues in administrative and criminal law contexts respectively. Although briefly mentioning the global and international context, the focus of this Article is the EU regulatory action, its outcome and critique, and possible future.

N-Iodosuccinimide (NIS) in pure trifluoroacetic acid (TFA) offers a time-efficient and general method for the iodination of a wide range of mono-and disubstituted benzenes at room temperature, as d ...

As a health professional, the EULAR congress is the place where I can get access to new and fresh rheumatology research of good quality. My presentation will take you through the possibilities the congress offers clinicians when it comes to different topics within the area of rheumatology. Further, my aim and hope is to give you a sense of what is in store for you during this year9s EULAR congress. People with rheumatic diseases today live their lives to a great extent having the diagnosis affecting their everyday life. The ability to work, interact with others or engaging in activities they want to, can be limited. So what do we need to know about them in order to provide the best possible treatment and rehabilitation? As a health professional clinician, I look forward to finding some of the answers to this during this congress. During the EULAR congress, we as health professionals have the possibility to contribute to and acquire research of good quality in rheumatology, on our way to give our patients the best possible treatment. Also, we have the possibility to contribute to the patientshealth, and I look forward to sessions touching health topics such as exercise. The quality of research and the variety of topics during this EULAR congress can give us a bigger set of tools to work with when we get back to our patients and continue our path towards the best possible treatment and health for this big and important group of patients. I hope that this session can provide an overview of what this years9 congress can offer from a clinical perspective. Disclosure of Interests: None declared

Background Persons with rheumatoid arthritis (RA) are at higher risk of sickness absence, and the probability of returning to work is lower compared to the general population [1]. In order for persons with RA to continue working, support from the social environment is claimed to be of importance [2]. However, this relation needs to be further investigated. Objectives To analyze how support from significant others affects the associations between disease related variables (medication, disease activity and activity limitations) at time for RA diagnosis and sickness absence one year after diagnosis. Methods Data were collected from 326 (71% women) patients in working age (18-63 years) included in the Swedish early RA cohort TIRA-2 [3] during 2006-2009. At time of inclusion, mean age was 50 years (SD=11), 89% were prescribed disease modifying anti-rheumatic drugs (DMARDs), mean disease activity score 28 joint count (DAS28) was 4.73 (SD=1.34), and mean score for activity limitation reported by Health Assessment Questionnaire (HAQ) was 0.91 (SD=0.60). The number of days with sickness absence during the first year after diagnosis and inclusion was retrieved from the Swedish Social Insurance Agency. Perceived support from significant others, family and friends separately, were self-reported by VAS scales, zero indicating no support and 100 indicating full support. The associations of disease activity, activity limitation and DMARD use with sickness absence and how these associations were moderated by support from significant others, were analyzed using zero-inflated negative binomial regression. Results Higher activity limitation (HAQ) was associated with lower risk of sickness absence (p Conclusion Support from significant others has an impact on previously known relationships between disease activity, use of DMARDs and sickness absence. Hence, support from significant others has the possibility to help decrease sickness absence among persons with RA one year after diagnosis. References [1] Hansen, SM., Hetland, ML., Pedersen, J., et al. Work ability in rheumatoid arthritis patients: a register study on the prospective risk of exclusion and probability of returning to work. Rheumatology. 2017;56(7):1135-1143. [2] Feddersen, H., Kristiansen, TM., Andersen, PT., et al. Construction of meaningful identities in the context of rheumatoid arthritis, motherhood and paid work: a meta-ethnography. Journal of Clinical Nursing. 2017;26(23-24):4117-4128. [3] Thyberg, I., Dahlstrm,., Bjrk, M., et al. Hand pains in women and men in early rheumatoid arthritis, a one year follow-up after diagnosis. The Swedish TIRA project. Disability and Rehabilitation. 2017;39(3):291-300. Disclosure of Interests None declared

Background:Participation in everyday life and the relationships between persons with rheumatoid arthritis (RA) and their significant others are often affected by the disease. Usually, both parts need to adapt to new roles [1]. However, the dyadic interaction between them in everyday life is yet to be understood on a deeper level.Objectives:To exploreI) How dyads consisting of persons with RA and their significant others comprehend support and participation in everyday life, andII) how the dyadic interaction can influence their experience of participation in everyday life.Methods:In-depth individual interviews were conducted both with the persons with RA 12-13 years after diagnosis and inclusion in the Swedish multicenter project TIRA-2 [2], and with their significant others as defined by the persons with RA. Demographic data and the Valued Life Activity Scale (VLA-swe) [3] was reported by the persons with RA. To avoid bias, the persons with RA and their significant others were interviewed by different researches. Data from the interviews were transcribed verbatim and content analysis with a dyadic approach was undertaken [4]. The process of coding and categorizing was discussed between the researchers. The study was approved by the Regional Ethics Committee at Linköping University (Dnr. 2018/158-31), all participants gave their written consent.Results:Three women and two men with RA and five significant others, all represented by spouses, participated (N=10). The age of the persons with RA ranged from 34 to 67 years and a majority experienced difficulties in ≥ 12 valued life activities.Three categories were revealed:1) A strong willpower affecting the dyadic relationship, meaning that the understanding within the dyads was that the persons with RA were not so keen to share status, which was mentioned in connection to tenacity and expectations.2) Being a support to each other, referring to the mutual understanding within the couples that there was a constant exchange of support, forming a basis for participation in everyday life. However, disagreement was expressed concerning an unequal amount of support.3) The dyads’ potential issues with awareness, addressing the difficulty in fully comprehending the impact of the diagnosis. The couples mentioned an unwillingness from the person with RA to share information, and the significant other viewing comments as complaining. This type of miscommunication was interpreted as a potential negative effect on participation in everyday life.Conclusion:A constant exchange of support within the dyads was evident. However, the dyadic relationships were often affected by the willpower of the persons with RA to be independent in everyday life. In addition, the dyads faced the concern of fully understanding the diagnosis. The results indicate further needs for interventions for both the persons with RA as well as the significant others, in order to boost the dyadic interaction, and thereby facilitate optimal participation in everyday life of persons with RA.References:[1]Brignon M, Vioulac C, Boujut E et al. (2019) Patients and relatives coping with inflammatory arthritis: care teamwork. Health Expect 2019;00:1-11[2]Thyberg I, Dahlström Ö, Björk M, et al. (2017) Hand pains in women and men in early rheumatoid arthritis, a one year follow-up after diagnosis. The Swedish TIRA project. Disabil Rehabil 2017;39(3):291-300[3]Björk M, Thyberg M, Valtersson, E et al. (2016) Validation and internal consistency of the Swedish version of the Valued Life Activities scale. Clin Rehabil 2016;30(12):1211-1219[4]Eiskovits Z, Koren C (2010) Approaches to and outcomes of dyadic interview analysis. Qual Health Res 2010;20(12):1642-55Disclosure of Interests:None declared

In just over 30 years, a global Anti-Money Laundering (AML) Regime has developed that is constantly being updated and expanded not only geographically but most importantly both in width and depth. Today, it affects a large part of modern society including both private and public actors and is key in a steadily growing number of interconnected areas, forming part of the broader EU Security Agenda. This chapter aims to illustrate the complex nature of the current AML Regime. Involving international, EU and national actors and laws, embracing public, private and penal rules, self-regulation and administrative and criminal law enforcement mechanisms, this complex regulatory field is now meant not only to prevent but also to control money laundering and terrorism financing.

SIGNIFICANT OTHERS AS BOTH BARRIERS AND FACILITATORS FOR PARTICIPATION IN DAILY ACTIVITIES IN PERSONS WITH EARLY RHEUMATOID ARTHRITIS - AN INTERVIEW STUDY WITHIN THE SWEDISH TIRA PROJECT

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with disability. Despite new treatments, pain and activity limitations are still present. Objectives: To describe how persons with RA experience and manage pain in their daily life. Methods: Seven semi-structured focus groups (FGs) were conducted and analyzed using content analysis. Results: The analysis revealed four categories: 1) Pain expresses itself in different ways referred to pain as overwhelming, aching or as a feeling of stiffness. 2) Mitigating pain referred to the use of heat, cold, medications and activities as distractions from the pain. 3) Adapting to pain referred to strategies employed as coping mechanisms for the pain, e.g. planning and adjustment of daily activities, and use of assistive devices. 4) Pain in a social context referred to the participants social environment as being both supportive and uncomprehending, the latter causing patients to hide their pain. Conclusions: Pain in RA is experienced in different ways. This emphasizes the multi-professional team to address this spectrum of experiences and to find pain management directed to the individual experience that also include the persons social environment. Funding Agencies|Swedish Association of Occupational Therapists

ERCP is the standard technique for dealing with pathology of the common bile duct, such as bile duct stones or strictures due to malignant or benign processes. However, ERCP in patients with surgically altered anatomy, such as Roux-en-Y gastric bypass (RYGBP), total gastrectomy, Billroth II procedure or Whipple procedure (Fig. 10.1), is challenging. Several more or less invasive methods have been described for endoscopic biliary interventions in these patients.

NOTES is believed to induce less surgical trauma than open and laparoscopic surgery. The degree of surgical trauma can be assessed by measuring serum levels of acute-phase proteins such as CRP and TNF-α. We conducted a prospective randomized survival trial in which the inflammatory responses after laparoscopic, open, and NOTES transgastric uterine horn resection were compared. The aim of this study was to investigate whether NOTES procedures induce less inflammatory response.Thirty pigs were randomized into three groups to undergo open, laparoscopic, or transgastric uterine horn resection. Weight, body temperature, and postoperative recovery were recorded and venous blood samples were taken for analysis of CRP and TNF-α at different time points. Analyses of CRP and TNF-α were performed using pig-specific ELISA assays.Procedure time was significantly longer for NOTES [median = 121 min (range = 94-155)] compared with that for open surgery [median = 22 min (14-27)] and laparoscopy [median = 37 min (20-45)] (p 0.0001). There was a nonsignificant tendency for shorter recovery time for the NOTES animals. Twenty-seven animals survived for 4 weeks. One animal in each group was euthanized prior to 4 weeks. All animals gained weight during the 4-week period with no significant differences. Only animals in the NOTES group showed a significant weight gain during the first postoperative week (p = 0.007). On postoperative day (POD) 1, CRP was significantly lower in the NOTES group compared with the open and laparoscopic groups (mean = 0.72 ± 0.22, 0.98 ± 0.26, and 0.97 ± 0.20, respectively; p = 0.048). The CRP levels were normalized on day 14. Throughout the study there were no significant changes in TNF-α levels in the laparoscopic and NOTES groups. At POD 3 the open surgery group showed significantly higher TNF-α levels than the other groups (p = 0.036).Despite the longer operating time, the transgastric NOTES approach seems to be less traumatic than open or laparoscopic uterine horn resection in this porcine model.

Background Peritoneal adhesions are a clinical problem. A key to the understanding of peritoneal adhesions is to study the healing of mesothelial cells within the peritoneal cavity following surgery. Transforming growth factor beta (TGF-βs) affects this healing process. The aim of this study was to investigate the effects of different concentrations of TGF-β1 on the healing rate and healing properties of mesothelial cells. Materials and methods Human mesothelial cells from peritoneal fluid were collected, cultured and a mechanical wound was created. The restoration of the mesothelial surface with and without increasing concentrations of TGF-β1 was monitored. Results The denuded area was restored within 24 h. The healing rate was most extensive between the first and second hour after the damage (61.9 ± 22.8 μm/h). No significant difference in healing rate were observed when increasing levels of TGF-β1 were used. However, higher concentrations of TGF-β1 increased cell size and the cells presented more fibroblast specific properties. Lower TGF-β1 concentrations increased the number of proliferating cells. Conclusions This study indicates the importance of high levels TGF-β1 in mesothelial cell healing, mainly by changing the actual healing properties of the cells. Elevated levels of TGF-β1 might promote mesothelial cell transition towards a more fibroblast-like appearance.

Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures induce a less pronounced postoperative inflammatory response than open or laparoscopic surgery, inflicting less trauma. In NOTES procedures, no skin incision is performed. We compare the inflammatory response added by the type of incision by measuring C-reactive protein (CRP) and tumors necrosis factor-alfa (TNF-α).Twenty-seven pigs were randomized to open surgical, laparoscopic, or transgastric NOTES abdominal access. After completion of the accesses, no surgery was performed. All accesses were left open for 40 minutes followed by closure, animals were survived for 7 days. Blood samples were drawn at the start of the accesses, at 20 and 40 minutes during the procedure, and at postoperative day (POD) 1, 3, and 7. Analyses of CRP and TNF-α were performed.CRP increased in all animals until POD1. This increase was greater in the open group (P = .006). No significant differences in CRP-levels were found at POD 1, 3, or 7. TNF-α showed a peak during the procedure, at 20 and 40 minutes, with normalization at POD1 for 1/3 of the open and laparoscopic animals, but not for the NOTES animals. Due to variations within the groups, no statistical difference was shown between them. At postmortem, 1/3 of the pigs in the laparoscopic and open groups had wound infections, while no NOTES animals showed infections.This study provides no statistically significant differences in inflammatory response after the different abdominal accesses. However, the lack of a TNF-α-peak in the NOTES group might indicate a less pronounced response, supporting the initial theories.

We developed a non-survival in vivo model for testing of gastric natural orifice translumenal endoscopic surgery (NOTES) closures based on the gastric yield pressure. The aim of this study was to test our model comparing different endoscopic closure techniques with surgical closure of a NOTES gastric incision.Laparotomy was performed in 30 pigs. One tube for air inflation and one manometry tube were inserted into the stomach via the pylorus, which was closed gas-tight, and the abdominal wall was closed. The stomach was inflated with air, and the gastroesophageal yield pressure was measured. A gastroscopy was performed, and a standard NOTES access was created followed by randomization to closure by surgical suturing, T-tags, Padlock-G over-the-scope (OTS)-clips, OVESCO OTS-clips, and traditional clips. All closures were tested twice with air insufflation. Gastric yield pressure or leak pressure of each closure was recorded.The mean baseline gastric yield pressure was 80.5 mm Hg. Post-closure yield pressure was 79.9 mm Hg. Leak test results after closure were as follows: surgery, 0/6 leaked; T-tags, 1/6 leaked before reaching yield pressure (56 mm Hg); Padlock-G, 2/5 leaked (71.5 mm Hg); OVESCO OTS-clips, 3/6 leaked (27.2 mm Hg); and traditional clips, 5/6 leaked (27.2 mm Hg). TAS T-tags and surgical closures leaked significantly less than the other groups (P=.01). Traditional clips and OVESCO OTS-clips leaked at significantly lower pressures than the other three groups (P=.007).This in vivo model using leak of the closure or the gastric yield pressure as endpoints for testing of the closure strength of a NOTES gastric access site seems to be reproducible. Our results support closure with T-tags and Padlock-G-clips over OVESCO OTS-clips and standard endoscopic clips.

Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures. NRF (Natl Research Foundation, S’pore) Accepted version

Fragment-based drug design (FBDD) is currently being implemented in drug discovery, creating a demand for developing efficient techniques for fragment screening. Due to the intrinsic weak or transient binding of fragments (mM-μM in dissociation constant (K(D))) to targets, methods must be sensitive enough to accurately detect and quantify an interaction. This study presents weak affinity chromatography (WAC) as an alternative tool for screening of small fragments. The technology was demonstrated by screening of a selected 23-compound fragment collection of documented binders, mostly amidines, using trypsin and thrombin as model target protease proteins. WAC was proven to be a sensitive, robust, and reproducible technique that also provides information about affinity of a fragment in the range of 1 mM-10 μM. Furthermore, it has potential for high throughput as was evidenced by analyzing mixtures in the range of 10 substances by WAC-MS. The accessibility and flexibility of the technology were shown as fragment screening can be performed on standard HPLC equipment. The technology can further be miniaturized and adapted to the requirements of affinity ranges of the fragment library. All these features of WAC make it a potential method in drug discovery for fragment screening.

The article analyses what the third EU Directive on AML (anti-money laundering) and risk management means in terms of democratic accountability when the banking sector is given a role that is traditionally the prerogative of the public actors. The comparison between the UK and Sweden on the private actors' role in various stages of the risk-based decision process shows that the procedures used could jeopardize the traditional liberal understanding of democratic accountability.

In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM–μM) small molecule–protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant ( K D ) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods ( R 2 = 0.995, P

Background Perforated duodenal ulcers can be treated with a covered stent. Stent migration is a severe complication, sometimes requiring surgery. Pyloric physiology during stent treatment has not been studied and mechanisms for migration are unknown. The aim of this study was to investigate the pyloric response to distention, mimicking stent treatment, using the EndoFLIP. Methods A nonsurvival study in five pigs was carried out, followed by a pilot study in one volunteer. Animals were gastroscoped during anaesthesia and the EndoFLIP was placed straddling the pylorus. Baseline distensibility readings were performed at stepwise balloon distentions to 20, 30, 40, and 50 mL, measuring pyloric cross-sectional area and pressure. Measurements were repeated after administration of a prokinetic drug and after a liquid meal. In the human study, readings were performed in conscious sedation at baseline and after stimulation with metoclopramide. Key results During baseline readings, the pylorus was shown to open more with increasing distention together with higher amplitude motility waves. Reaching maximum distention-volume (50 mL), pyloric pressure increased significantly (P = 0.016), and motility waves disappeared. After prokinetic stimulation, the pressure decreased and the motility waves increased in frequency and amplitude. After food stimulation, the pressure stayed low and the motility showed increase in amplitude. During both tests, the pylorus showed higher pressure and lack of motility waves at maximum probe distention. Conclusions and inferences The pylorus seems to act as a sphincter at low distention but when further dilated starts acting as a pump. Fully distended the pyloric motility disappears and the pressure remains high, suggesting that a stent with high-radial force might show less migration.

Background Current devices for hemostasis in flexible endoscopy are inferior to methods used during open or laparoscopic surgery and might be ineffective for natural orifice transluminal endoscopic surgery. Objective To compare new flexible bipolar forceps (FBF), designed principally for natural orifice transluminal endoscopic surgery, with laparoscopic bipolar forceps (LBF) for hemostasis of intra-abdominal porcine arteries. Setting Surgical laboratories in Europe and the United States. Design and Interventions New FBF for hemostasis (3.7-mm diameter), featuring electrode isolation, were compared with rigid 5-mm LBF (ERBE BiClamp LAP forceps) at recommended settings. A porcine model of acute hemostasis was prepared by suturing the uterine horns and cecum to the abdominal wall, exposing uterine arteries, ovarian pedicles, cecal mesenteric bundles, and the inferior mesenteric artery. This allowed access to 10 vessels in each pig by transabdominal laparoscopic devices or a transgastric double-channel gastroscope. Vessels were measured, coagulated at 4 and more points, and transected. Blood pressure was increased to more than 200 mm Hg for 10 minutes by administering phenylephrine. Delayed bleeding was identified. Main Outcome Measurements In 7 pigs, a total of 65 vessels (1.5-6.0 mm) were randomly allocated to FBF (n = 32) or LBF (n = 33). Successful hemostasis both before and after blood pressure increase was equivalent between the 2 groups (before: 88% FBF vs 88% LBF, not significant [NS]; after: 97% FBF vs 94% LBF, NS). With FBF, the number of seals per vessel was 4.8 vs 4.4 with LBF (NS). The energy used to create FBF seals was 19.8 J vs 38.2 J for LBF ( P Limitations Results from porcine studies may not reflect patient outcomes. Conclusions In a porcine model, transgastric FBF endoscopic hemostasis was as effective as conventional laparoscopic hemostasis using LBF across a wide range of vessels.

Anti-adhesion drugs may be an alternative to antibiotics to control infection of micro-organisms. The well-characterized interaction between cholera toxin and the cellular glycolipid GM1 makes it an attractive model for inhibition studies in general. In this report, we demonstrate a high-performance liquid affinity chromatography approach called weak affinity chromatography to evaluate cholera toxin inhibitors. The cholera toxin B-subunit was covalently coupled to porous silica and a (weak) affinity column was produced. The K(D) values of galactose and meta-nitrophenyl alpha-D-galactoside were determined with weak affinity chromatography to be 52 and 1 mM, respectively, which agree well with IC(50) values previously reported. To increase inhibition potency multivalent inhibitors have been developed and the interaction with multivalent glycopolypeptides was also evaluated. The affinity of these compounds was found to correlate with the galactoside content but K(D) values were not obtained because of the inhomogeneous response and slow off-rate from multivalent interactions. Despite the limitations in obtaining direct K(D) values of the multivalent galactopolypeptides, weak affinity chromatography represents an additional and valuable tool in the evaluation of monovalent as well as multivalent cholera toxin inhibitors. It offers multiple advantages, such as a low sample consumption, high reproducibility and short analysis time, which are often not observed in other methods of analysis.

Background Peritoneal fibrinolysis is crucial in the peritoneal healing processes and subsequent adhesion formation. During conventional surgery, the peritoneal fibrinolytic system is rapidly disturbed. Short-term laparoscopy does not seem to affect peritoneal fibrinolysis. The aim of the present study was to assess the effect of prolonged laparoscopic surgery on peritoneal fibrinolysis. Methods Twelve consecutive patients undergoing laparoscopic gastric bypass surgery for morbid obesity were included in the study. During the procedure, biopsies of the parietal peritoneum were taken at the start of the procedure and each 45 min afterward. Tissue samples were homogenized and tissue-type plasminogen activator (tPA) antigen, tPA activity, urokinase-type PA antigen, and plasminogen activating inhibitors type 1 antigen were measured using commercial assay techniques. Results Both tPA antigen and its activity progressively decreased during the procedure, reaching significant levels after 90 min of surgery. The levels of uPA antigen and plasminogen activating inhibitors antigen did not significantly change throughout the procedure. Conclusions As for conventional surgery, prolonged laparoscopic surgery causes a decreased fibrinolytic activity in the peritoneum due to decreased tPA levels.

Background Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure. Objective The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study. Setting University hospitals in the United States and Europe. Design and Interventions After creating a 4-cm linear colon perforation, the animals were randomized to either endoscopic or surgical closure. The total procedure time from the beginning of perforation to the completion of procedure was measured. The animals were euthanized after 2 weeks to evaluate healing, unless there was a complication. Results Fifty-four animals were randomized to either surgical or endoscopic closure of colon perforation. Eight animals developed complications, and 7 of these were euthanized before 2 weeks. Twenty-three animals in each group survived for 2 weeks. Surgical closure of the perforation was successful in all animals in that group, and endoscopic closure was successful in 25 of the 27 animals. The median procedure time was shorter in the surgery group compared to the endoscopy group (35 vs 44 minutes, P = .016). Peritonitis, local adhesions, and leak test results were comparable in both groups. Distant adhesions were less frequent in the endoscopic closure group (26.1% vs 56.5%, P = .03). Five of the 186 T-tags (2.7%) were noted in the adjacent viscera. Limitation This porcine study does not mimic clean colon perforation in humans; it mimics dirty colon perforation in humans. Conclusions Endoscopic closure of a 4-cm colon perforation was comparable to surgery, and this technique can be potentially used for closure of intentional or inadvertent colon perforations.