On the effect of flavonoids and dietary fibre in lingonberries on atherosclerotic plaques, lipid profiles and gut microbiota composition in Apoe-/- mice.

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.

Simultaneous quantification of trimethylamine N-oxide, trimethylamine, choline, betaine, creatinine, and propionyl-, acetyl-, and L-carnitine in clinical and food samples using HILIC-LC-MS.

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.

Stent treatment or surgical closure for perforated duodenal ulcers: a prospective randomized study.

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.

Exploring Multi-Subsite Binding Pockets in Proteins: DEEP-STD NMR Fingerprinting and Molecular Dynamics Unveil a Cryptic Subsite at the GM1 Binding Pocket of Cholera Toxin†B.

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.

Hepatitis E virus genotype 3 is associated with gallstone-related disease.

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.

Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins.

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.

Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules.

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 (KD) 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<0.0001).

Stress response and well-being after open, laparoscopic, and NOTES transgastric uterine horn resection in a randomized porcine model.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A dyadic exploration of support in everyday life of persons with RA and their significant others.

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.

A randomized trial comparing rates of abdominal contamination and postoperative infection among natural orifice transluminal endoscopic surgery, laparoscopic surgery, and open surgery in pigs.

BACKGROUND: Bacterial contamination of the abdominal cavity and infectious complications have been debated concerning transgastric natural orifice transluminal endoscopic surgery (NOTES) procedures. OBJECTIVE: The aim of this study was to compare bacterial contamination of the abdominal cavity and clinically relevant infections after open, laparoscopic, and transgastric NOTES procedures. DESIGN: Randomized survival study in a porcine model. SETTING: Animal laboratory at a university hospital. INTERVENTION: Thirty pigs were randomized to open, laparoscopic, or transgastric NOTES uterine horn resection under sterile conditions. Bacterial cultures were obtained from the pelvic area immediately at entry of the abdominal cavity and just before closure. The left uterine horn was dissected and ligated. The animals survived for 4 weeks. At necropsy, bacterial culture was obtained from the pelvic area. MAIN OUTCOME MEASUREMENTS: Perioperative: operation time and incision length, bacterial growth in abdominal samples. Postoperative: infections or complications, weight gain. Necropsy: signs of peritonitis or infection, abdominal bacterial growth. RESULTS: Procedure time was significantly longer for transgastric NOTES. At the start of the procedure, 4 of the NOTES animals showed positive cultures, but only 1 showed positive cultures at the end. No open surgery or laparoscopic surgery animals showed positive cultures at these time points. At necropsy, none of the animals in the NOTES group showed bacterial growth, whereas 4 open surgery animals and 3 laparoscopic surgery animals had positive cultures. Four of these animals (2 from each group) had concurrent wound infections. LIMITATIONS: Small sample size and lack of power calculation. CONCLUSION: This study indicates that clinically relevant infections are rare after transgastric NOTES procedures despite evidence of bacterial contamination and longer operating times.

Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies.

By examining the interactions between the protein hen egg-white lysozyme (HEWL) and commercially available and chemically synthesized carbohydrate ligands using a combination of weak affinity chromatography (WAC), NMR spectroscopy and molecular simulations, we report on new affinity data as well as a detailed binding model for the HEWL protein. The equilibrium dissociation constants of the ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The structures of two HEWL-disaccharide complexes in solution were deduced by NMR spectroscopy using (1)H saturation transfer difference (STD) effects and transferred (1)H,(1)H-NOESY experiments, relaxation-matrix calculations, molecular docking and molecular dynamics simulations. In solution the two disaccharides ß-d-Galp-(1→4)-ß-D-GlcpNAc-OMe and ß-D-GlcpNAc-(1→4)-ß-D-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the glycosidic linkage between the two sugar residues. Intermolecular hydrogen bonding and CH/π-interactions form the basis of the protein-ligand complexes in a way characteristic of carbohydrate-protein interactions. Molecular dynamics simulations with explicit water molecules of both the apo-form of the protein and a ligand-protein complex showed structural change compared to a crystal structure of the protein. The flexibility of HEWL as indicated by a residue-based root-mean-square deviation analysis indicated similarities overall, with some residue specific differences, inter alia, for Arg61 that is situated prior to a flexible loop. The Arg61 flexibility was notably larger in the ligand-complexed form of HEWL. N,N'-Diacetylchitobiose has previously been observed to bind to HEWL at the B and C sites in water solution based on (1)H NMR chemical shift changes in the protein whereas the disaccharide binds at either the B and C sites or the C and D sites in different crystal complexes. The present study thus highlights that protein-ligand complexes may vary notably between the solution and solid states, underscoring the importance of targeting the pertinent binding site(s) for inhibition of protein activity and the advantages of combining different techniques in a screening process.

Stenting for colorectal cancer obstruction compared to surgery--a study of consecutive patients in a single institution.

BACKGROUND: Colonic obstruction is a common complication to colorectal cancer and surgical treatment is associated with high morbidity and mortality. Stenting has emerged as an alternative to surgery. The aim of this study was to compare short-term morbidity, mortality and hospital stay between treatment with self-expandable metallic stent and emergency surgery performed at our department during a 5-year period in a non-randomized setting. METHODS: Patients with colonic obstruction due to rectal or colon cancer referred to the Endoscopic Unit or Surgical Department for insertion of a colonic stent between 1 August 2003 and 1 August 2008 were prospectively registered and followed (n = 112). A control group was identified using the hospital records of operations with the International Classification Code-10 (ICD-10) for bowel obstruction and colorectal cancer (n = 60). Age, gender, indication, preoperative investigations, surgical procedure, complications and procedure-related mortality were registered. Patients were followed in accordance with local guidelines. RESULTS: The complication rate was similar in the two groups, although there was a trend toward a higher number of severe complications in the surgical group. The hospital stay was significantly lower in the stent group, median of 4 vs. 9 days (p < 0.0001). The procedure-related mortality was lower in the stent group; 7% vs. 20% (p < 0.05). CONCLUSIONS: Stenting can be safely performed with lower or similar complication rate and lower mortality rate compared to surgery and results in significantly shorter hospital stay. The results support stenting as the treatment of choice in patients with acute colonic obstruction, especially in disseminated disease.

Effects of Whole Brown Bean and Its Isolated Fiber Fraction on Plasma Lipid Profile, Atherosclerosis, Gut Microbiota, and Microbiota-Dependent Metabolites in Apoe-/- Mice.

The health benefits of bean consumption are widely recognized and are largely attributed to the dietary fiber content. This study investigated and compared the effects of whole brown beans and an isolated bean dietary fiber fraction on the plasma lipid profile, atherosclerotic plaque amount, gut microbiota, and microbiota-dependent metabolites (cecal short-chain fatty acids (SCFAs) and plasma methylamines) in Apoe-/- mice fed high fat diets for 10.5 weeks. The results showed that both whole bean and the isolated fiber fraction had a tendency to lower atherosclerotic plaque amount, but not plasma lipid concentration. The whole bean diet led to a significantly higher diversity of gut microbiota compared with the high fat diet. Both bean diets resulted in a lower Firmicutes/Bacteroidetes ratio, higher relative abundance of unclassified S24-7, Prevotella, Bifidobacterium, and unclassified Clostridiales, and lower abundance of Lactobacillus. Both bean diets resulted in higher formation of all cecal SCFAs (higher proportion of propionic acid and lower proportion of acetic acid) and higher plasma trimethylamine N-oxide concentrations compared with the high fat diet. Whole beans and the isolated fiber fraction exerted similar positive effects on atherosclerotic plaque amount, gut microbiota, and cecal SCFAs in Apoe-/- mice compared with the control diets.

Weak affinity chromatography as a new approach for fragment screening in drug discovery.

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.

Synthesis and affinity evaluation of a small library of bidentate cholera toxin ligands: towards nonhydrolyzable ganglioside mimics.

A small library of nonhydrolyzable mimics of GM1 ganglioside, featuring galactose and sialic acid as pharmacophoric carbohydrate residues, was synthesized and tested. All compounds were synthesized from readily available precursors using high-performance reactions, including click chemistry protocols, and avoiding O-glycosidic bonds. Some of the most active molecules also feature a point of further derivatization that can be used for conjugation with polyvalent aglycons. Their affinity towards cholera toxin was assessed by weak affinity chromatography, which allowed a systematic evaluation and selection of the best candidates. Affinity could be enhanced up to one or two orders of magnitude over the affinity of the individual pharmacophoric sugar residues.

A randomized comparison of a new flexible bipolar hemostasis forceps designed principally for NOTES versus a conventional surgical laparoscopic bipolar forceps for intra-abdominal vessel sealing in a porcine model.

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 < .05). 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.

Toward high-throughput drug screening on a chip-based parallel affinity separation platform.

High-throughput screening of compound libraries, including the study of fragments, has become one of the cornerstones in modern drug discovery research. During this process hits are defined that may be developed into valuable leads and eventually into possible drug candidates. In this paper, we have demonstrated that parallel zonal weak affinity chromatography in microcolumns on a chip offers a possible screening format for weakly binding ligands toward a protein target. We used albumin as a model system because this transport protein is well established as a binder (both weak and strong) for drug substances. Bovine serum albumin was immobilized on microparticulate diolsilica particles and then packed into a 24-channel cartridge, which served as the separation platform. Analysis of the obtained chromatograms yielded information about affinity even in the millimolar range. Employing this approach, thousands of substances can be screened in just a day. We feel confident that zonal affinity chromatography will provide a useful technology in the future for performing high-throughput screening.

From carbohydrates to fat: Trends in food intake among Swedish nutrition students from 2002 to 2017.

Earlier studies have implied a change in dietary habits of the Swedish population towards a low carbohydrate, high fat diet. Questions have been raised about the development in recent years and potential health effects. We have investigated the dietary intake of Swedish female students enrolled in a university nutrition course between 2002 and 2017. The students carried out self-reporting of all food and drink intake over one weekday and one weekend day. Intake of macronutrients (E%) and micronutrients were calculated for the whole period while statistical analysis was performed for changes between 2009 and 2017 (729 women). Results showed significant changes in carbohydrate intake (from 47.0 to 41.4 E%) and fat intake (from 31.7 to 37.5 E%). Carbohydrate intake was significantly lower than the Nordic Nutrition Recommendations (45-60 E%). However, daily fiber intake remains high (3.0 g/MJ) in a national context, and intake of vitamin D and folate appears to increase during the period. The results suggest that the observed national transition from carbohydrate to fat intake persists, and that it might be especially evident among individuals interested in food and nutrition. Considering the fiber and micronutrient intake, the change is not necessarily unfavorable for this particular group.

Bacterial colonization of the stomach and duodenum in a Swedish population with and without proton pump inhibitor treatment.

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 < 0.0001). Duodenal cultures were positive in 20 of 24 with PPI and 8 of 25 without (P < 0.0001). The most commonly identified bacterial species were oral strains of Streptococcus, followed by Neisseria and Haemophilus influenzae. Of 103 patients, 10 had a positive urease test, indicating H. pylori infection, 1 with PPI and 9 without. CONCLUSIONS: Bacterial growth in the stomach and duodenum is more common in patients with PPI treatment. The dominating bacterial species found in the stomach and duodenum originates from the oropharynx. Clinical trials registry: Trial registration number 98041 in Researchweb (FoU in Sweden).

Significant others' influence on participation in everyday life - the perspectives of persons with early diagnosed rheumatoid arthritis.

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.