Targeting NOX2 with Bivalent Small-Molecule p47phox-p22phox Inhibitors.

Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) is an enzymatic complex whose function is the regulated generation of reactive oxygen species (ROS). NOX2 activity is central to redox signaling events and antibacterial response, but excessive ROS production by NOX2 leads to oxidative stress and inflammation in a range of diseases. The protein-protein interaction between the NOX2 subunits p47phox and p22phox is essential for NOX2 activation, thus p47phox is a potential drug target. Previously, we identified 2-aminoquinoline as a fragment hit toward p47phoxSH3A-B and converted it to a bivalent small-molecule p47phox-p22phox inhibitor (Ki = 20 µM). Here, we systematically optimized the bivalent compounds by exploring linker types and positioning as well as substituents on the 2-aminoquinoline part and characterized the bivalent binding mode with biophysical methods. We identified several compounds with submicromolar binding affinities and cellular activity and thereby demonstrated that p47phox can be targeted by potent small molecules.

An ecosystem-wide reproductive failure with more snow in the Arctic.

2018: Arctic researchers have just witnessed another extreme summer-but in a new sense of the word. Although public interest has long been focused on general warming trends and trends towards a lower sea ice cover in the Arctic Ocean, this summer saw the realization of another predicted trend: that of increasing precipitation during the winter months and of increased year-to-year variability. In a well-studied ecosystem in Northeast Greenland, this resulted in the most complete reproductive failure encountered in the terrestrial ecosystem during more than two decades of monitoring: only a few animals and plants were able to reproduce because of abundant and late melting snow. These observations, we suggest, should open our eyes to potentially drastic consequences of predicted changes in both the mean and the variability of arctic climate.

Fixed Combination Aerosol Foam Calcipotriene 0.005% (Cal) Plus Betamethasone Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for Psoriasis Vulgaris: A Randomized, Double-blind, Multicenter, Three-arm, Phase 2 Study.

OBJECTIVE: To evaluate the efficacy of fixed combination aerosol foam calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD). DESIGN: Patients were randomized (100:101:101) to receive Cal/BD foam, Cal foam, or BD foam once daily for four weeks. SETTING: Twenty-eight United States centers. PARTICIPANTS: 302 patients (≥18 years) with Psoriasis vulgaris (plaque Psoriasis; ≥mild disease severity by physicians global assessment). MEASUREMENTS: Treatment success of the body ("clear"/"almost clear" from baseline moderate/severe disease; "clear" from baseline mild disease). Involved scalp treatment success was an additional endpoint. RESULTS: Most patients (76%) had moderate Psoriasis of the body (66% for scalp). At Week 4, 45 percent of Cal/BD foam patients achieved treatment success, significantly more than Cal foam (14.9%; OR 4.34 [95%CI 2.16,8.72] P<0.001) or BD foam (30.7%; 1.81 [1.00,3.26] P=0.047). Fifty-three percent of Cal/BD foam patients achieved treatment success of the scalp, significantly greater than Cal foam (35.6%; 1.91 [1.09,3.35] P=0.021), but not BD foam (47.5%; 1.24 [0.71,2.16] P=0.45). Mean modified Psoriasis area and severity index (population baseline 7.6) improved in all groups, with statistically significant differences in Week 4 Cal/BD foam score (2.37) versus Cal foam (4.39; mean difference -2.03 [-2.63][-1.43] P<0.001) and BD foam (3.37; -1.19 [-1.80][-0.59] P<0.001). Four (Cal/BD), 10 (Cal), and 8 (BD) adverse drug reactions were reported. CONCLUSION: Cal/BD foam was significantly more effective than Cal foam and BD foam in providing treatment success at Week 4 and effective on involved scalp. TRIAL REGISTRATION: NCT01536938.

Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea.

OBJECTIVE: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. METHODS: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. RESULTS: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups. CONCLUSION: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial.

OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. DESIGN: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. RESULTS: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. CONCLUSIONS: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

A Novel Aerosol Foam Formulation of Calcipotriol and Betamethasone Has No Impact on HPA Axis and Calcium Homeostasis in Patients With Extensive Psoriasis Vulgaris.

BACKGROUND: Fixed combination calcipotriol 50 µg/g (Cal; as hydrate) plus betamethasone 0.5 mg/g (as dipropionate; BD) has been formulated in an innovative aerosol foam. OBJECTIVE: To assess systemic safety of Cal/BD aerosol foam. METHODS: In a multicentre, single-arm, open-label, maximal-use systemic-exposure trial, adult patients with moderate to severe, extensive psoriasis (15%-30% of body surface area, including ≥30% of scalp) applied Cal/BD foam once daily. Endpoints were week 4 abnormal adrenocorticotropic hormone (ACTH) challenge test and change in albumin-corrected serum calcium, 24-hour urinary calcium excretion, and urinary calcium-creatinine ratio. RESULTS: 35 patients reaching week 4 exhibited normal ACTH responses. At week 4, changes in calcium homeostasis were minor and not clinically relevant; no patients experienced elevations above normal. Disease severity generally improved, and 49% of patients achieved treatment success according to the Physician's Global Assessment of Disease Severity. CONCLUSION: No clinically relevant HPA axis or calcium homeostasis impact was observed with 4 weeks of once-daily Cal/BD foam in patients with extensive psoriasis vulgaris.

Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris--A randomized phase II study.

BACKGROUND: An aerosol foam formulation of fixed combination calcipotriene 0.005% (as hydrate; Cal) plus betamethasone dipropionate 0.064% (BD) was developed to improve psoriasis treatment. OBJECTIVES: To compare the efficacy and safety of Cal/BD aerosol foam with Cal/BD ointment after 4 weeks. METHODS: In this Phase II, multicenter, investigator-blind, 4-week trial, adult patients with psoriasis vulgaris were randomized to Cal/BD aerosol foam, Cal/BD ointment, aerosol foam vehicle or ointment vehicle (3:3:1:1). The primary efficacy endpoint was the proportion of patients at week 4 who achieved treatment success (clear or almost clear with at least a two-step improvement) according to the physician's global assessment of disease severity. RESULTS: In total, 376 patients were randomized. At week 4, significantly more patients using Cal/BD aerosol foam achieved treatment success (54.6% versus 43.0% [ointment]; p = 0.025); mean modified (excluding the head, which was not treated) psoriasis area and severity index score was significantly different between Cal/BD aerosol foam and Cal/BD ointment (mean difference -0.6; p = 0.005). Rapid, continuous itch relief occurred with both active treatments. One adverse drug reaction was reported with Cal/BD aerosol foam (application site itch). CONCLUSIONS: Cal/BD aerosol foam demonstrates significantly greater efficacy and similar tolerability compared with Cal/BD ointment for psoriasis treatment.

Efficacy and Safety of Calcipotriene Plus Betamethasone Dipropionate Aerosol Foam in Patients With Psoriasis Vulgaris--a Randomized Phase III Study (PSO-FAST).

INTRODUCTION: An innovative aerosol foam formulation of calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD) designed to improve treatment outcomes. OBJECTIVE: To compare the efficacy and safety of Cal/BD aerosol foam with aerosol foam vehicle in patients with psoriasis. DESIGN: Phase III, double-blind, randomized PSO-FAST (Cal/BD foam in PSOriasis vulgaris, a Four-week, vehicle-controlled, efficacy And Safety Trial) study recruited patients with ≥ mild severity psoriasis of the trunk and/or limbs from 27 US outpatient sites (NCT01866163). Patients were randomized (3:1) to Cal/BD foam or vehicle once-daily for 4 weeks. PRIMARY OUTCOME: proportion of patients at week 4 who achieved treatment success according to physician's global assessment. SECONDARY OUTCOMES: modified (excluding head) psoriasis area and severity index (mPASI) and patient's assessment of itch (visual analog scale). Safety was monitored by adverse events/calcium homeostasis. RESULTS: 426 patients enrolled between June and October 2013 (Cal/BD foam, n=323; vehicle, n=103). At week 4, significantly more patients using Cal/BD foam achieved treatment success versus vehicle (53.3 versus 4.8%; OR 30.3, 95% CI 9.7,94.3; P < .001) and mean mPASI score was significantly lower for patients using Cal/BD foam than vehicle (2.0 versus 5.5; adjusted difference -3.3, P <.001). Significantly greater itch relief was observed for patients using Cal/BD foam than vehicle (P = .010 at day 3, P < .001 from day 5). Adverse drug reactions were reported in 10 Cal/BD foam patients (3.1%) and two vehicle patients (1.9%); events occurred in one patient each except application site pain (Cal/BD foam, two patients; vehicle, one patient). There were no clinically significant changes in calcium homeostasis. CONCLUSIONS: Cal/BD foam was efficacious, achieved rapid itch relief and was well tolerated in patients with body psoriasis. This innovative aerosol foam formulation is expected to become a valuable treatment option.

The self-efficacy in patient-centeredness questionnaire - a new measure of medical student and physician confidence in exhibiting patient-centered behaviors.

BACKGROUND: Patient-centered communication is a core competency in modern health care and associated with higher levels of patient satisfaction, improved patient health outcomes, and lower levels of burnout among physicians. The objective of the present study was to develop a questionnaire assessing medical student and physician self-efficacy in patient-centeredness (SEPCQ) and explore its psychometric properties. METHODS: A preliminary 88-item questionnaire (SEPCQ-88) was developed based on a review of the literature and medical student portfolios and completed by 448 medical students from Aarhus University. Exploratory Principal Component analysis resulted in a 27-item version (SEPCQ-27) with three underlying self-efficacy factors: 1) Exploring the patient perspective, 2) Sharing information and power, and 3) Dealing with communicative challenges. The SEPCQ-27 was completed by an independent sample of 291 medical students from 2 medical schools and 101 hospital physicians. RESULTS: Internal consistencies of total and subscales were acceptable for both students and physicians (Cronbach's alpha (range): 0.74-0.95). There were no overall indications of gender-related differential item function (DIF), and a Confirmatory Factor Analysis (CFA) indicated good fit (CFI = 0.98; NNFI = 0.98; RMSEA = 0.05; SRMR = 0.07). Responsiveness was indicated by increases in SEPCQ scores after a course in communication and peer-supervision (Cohen's d (range): 0.21 to 0.73; p: 0.053 to 0.001). Furthermore, positive associations were found between increases in SEPCQ-scores and course-related motivation to learn (medical students) and between SEPCQ scores and years of clinical experience (physicians). CONCLUSIONS: The final SEPCQ-27 showed satisfactory psychometric properties, and preliminary support was found for its construct validity, indicating that the SEPCQ-27 may be a valuable measure in future patient centered communication training and research.

A 3.5 year diary study: Remembering and life story importance are predicted by different event characteristics.

Forty-five participants described and rated two events each week during their first term at university. After 3.5 years, we examined whether event characteristics rated in the diary predicted remembering, reliving, and life story importance at the follow-up. In addition, we examined whether ratings of life story importance were consistent across a three year interval. Approximately 60% of events were remembered, but only 20% of these were considered above medium importance to life stories. Higher unusualness, rehearsal, and planning predicted whether an event was remembered 3.5 years later. Higher goal-relevance, importance, emotional intensity, and planning predicted life story importance 3.5 years later. There was a moderate correlation between life story importance rated three months after the diary and rated at the 3.5 year follow-up. The results suggest that autobiographical memory and life stories are governed by different mechanisms and that life story memories are characterized by some degree of stability.

Efficacy of an innovative aerosol foam formulation of fixed combination calcipotriol plus betamethasone dipropionate in patients with psoriasis vulgaris.

BACKGROUND AND OBJECTIVE: The antipsoriatic effect of an innovative aerosol foam formulation of fixed combination calcipotriol 50 µg/g (as hydrate; Cal) and betamethasone 0.5 mg/g (as dipropionate; BD) was explored in order to compare the effect with that of the first-line treatment Cal/BD ointment. METHODS: This was a Phase IIa, single-centre, investigator-blinded, exploratory study, with intra-individual comparison using a modified psoriasis plaque test. Patients were treated once daily (6 days/week) for 4 weeks with Cal/BD foam, Cal/BD ointment, BD foam and Cal/BD foam vehicle, randomized to four plaque test sites (5 cm(2) each). The primary efficacy endpoint was change in total clinical score (TCS; sum of erythema, scaling and lesional thickness). Secondary endpoints included ultrasonographic changes in total skin thickness and echo-poor band thickness, and adverse events. RESULTS: Twenty-four patients, median age 52.5 years (range 21-75), completed this study. At week 4, test sites treated with Cal/BD foam had a significantly greater decrease in mean (±SD) TCS (-6.00 ± 1.27) versus those treated with Cal/BD ointment (-5.25 ± 1.78; difference -0.75; 95 % CI -1.46 to -0.04; p = 0.038), BD foam (-4.96 ± 1.85; difference -1.04; 95 % CI -1.75 to -0.33; p = 0.005) or foam vehicle (-1.88 ± 1.12; difference -4.13; 95 % CI -4.83 to -3.42; p < 0.001). Total skin thickness and echo-poor band thickness of Cal/BD foam-treated sites were reduced to a greater extent than those treated with comparators. Eleven patients reported 17 adverse events, the most frequent being headache (five patients). There were no lesional/perilesional adverse events or adverse drug-related events. CONCLUSIONS: Cal/BD foam demonstrated a significant improvement in antipsoriatic effect over Cal/BD ointment, BD foam and foam vehicle alone.

Chronic non-bloody diarrhoea: a prospective study in Malmö, Sweden, with focus on microscopic colitis.

BACKGROUND: Chronic non-bloody diarrhoea affects up to 5% of the population. Microscopic colitis is one of the most common causes, encompassing the subtypes collagenous colitis and lymphocytic colitis. The diagnosis of microscopic colitis is made by histological examination of colonic mucosal biopsy specimens. The aim of this investigation was to determine whether laboratory parameters or questions about disease history or concomitant disease could be helpful in discriminating patients with MC from those with a histologically normal colonic mucosa. FINDINGS: Patients admitted for colonoscopy because of chronic non-bloody diarrhoea (>2 loose stools for >3 weeks) at endoscopy units in Malmö during 2007 and 2009, were enrolled. A total number of 78 patients were included (60 women, 18 men, median age 59, IQR 45-69 years). Out of these 78, 15 patients (19%) had microscopic colitis (CC; n = 10, LC; n = 5). MC was especially prevalent in patients above the age of 50 (25%). No differences were found between those with normal histology and MC in laboratory analyses (inflammatory and liver parameters). Neither were differences shown in questions regarding symptoms, environmental factors or concomitant diseases except for an association with celiac disease (p = 0.019) and a trend maybe indicating an inverse association with appendectomy (p = 0.057). CONCLUSIONS: Microscopic colitis is associated with female gender, celiac disease and consumption of NSAIDs. Trends were observed indicating that age above 50 years, acute onset and absence of appendectomy may be associated with MC. No associations were observed with other symptoms, calprotectin levels or liver parameters.

The emotional content of life stories: positivity bias and relation to personality.

We examined whether past and future negative life story events, compared to past and future positive events, were less likely to be related to life story chapters and situated at a greater temporal distance from the present. We also examined relations between life stories and personality traits. Three hundred ten students and 160 middle-aged adults completed a measure of personality traits and identified chapters as well as past and future events in their life story. All life story components were rated on emotion and age. Negative future events were less likely to be a continuation of chapters and were more temporally distant than positive future events. Extraversion and Conscientiousness were related to more positive life stories, and Neuroticism was related to more negative life stories. This suggests that the life story is positively biased by minimising the negative future, and that the construction of life stories is related to personality traits.

Effect of calcipotriene plus betamethasone dipropionate topical suspension on the hypothalamic-pituitary-adrenal axis and calcium homeostasis in subjects with extensive psoriasis vulgaris: an open, non-controlled, 8-week trial.

BACKGROUND: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate is effective and safe in the treatment of psoriasis on the body and scalp within the general psoriasis patient population. OBJECTIVE: To evaluate the systemic effects of once-daily use of two-compound topical suspension/gel on the hypothalamic-pituitary-adrenal (HPA) axis and calcium homeostasis in subjects with extensive psoriasis vulgaris. METHODS: An open-label, single-group, 8-week trial in 43 subjects with extensive psoriasis covering 15-30% of the body surface area. Blood and 24-hour urine samples were collected and a standard-dose adrenocorticotropic hormone (ACTH) stimulation test was performed at baseline, weeks 4 and 8. Primary endpoints were serum cortisol 30 minutes after ACTH injection (HPA axis response abnormal at serum cortisol ≤18 µg/dL) and changes from baseline in albumin-corrected serum calcium (sCa), 24-hour urinary calcium excretion (24hCa) and urine calcium:creatinine ratio (Ca:Crea). RESULTS: Two (4.7%) subjects showed signs of adrenal suppression based on the ACTH stimulation test results at week 4; both were withdrawn from treatment and had normal serum cortisol 30-minute values at follow-up 4 weeks later. None of the subjects who continued treatment to week 8 showed signs of adrenal suppression. There were no clinically relevant mean changes from baseline to weeks 4 and 8 in sCa, 24hCa or Ca:Crea and no subject had sCa above the reference range. CONCLUSION: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate may be applied once daily to extensive psoriasis vulgaris without generally causing adrenal suppression or disturbance of calcium homeostasis, consistent with previous findings. In a small number of patients with extensive psoriasis treated with large volumes of topical suspension, adrenal suppression may be observed. In the real-world setting, it is anticipated that systemic side-effects would occur in only a few cases within the general psoriasis patient population. ClinicalTrials.gov Identifier:

Are collagenous and lymphocytic colitis different aspects of the same disease?

OBJECTIVE: Collagenous colitis (CC) and lymphocytic colitis (LC) are two subtypes of microscopic colitis (MC). Even though they most often are described as different entities they share many clinical and histological features. The aim of this study was to investigate the occurrence of conversion between CC and LC in a larger cohort of patients. MATERIALS AND METHODS: All 664 patients in our Pathology register with a diagnosis of CC and LC were scrutinized and those where additional endoscopies had been carried out were included, and their biopsies were re-examined. RESULTS: Sixty-five patients (55 women, 10 men, median age 58 years; range 29-86) fulfilled our criteria for inclusion. The primary diagnosis was CC in 47 patients (39 women, 8 men, median age 58 years; range 29-86) and LC in 18 patients (16 women, 2 men, median age 58 years; range 33-74). Conversion occurred in nine of the 65 patients (14%, all women, median age 59 years; range 41-72), three from CC to LC and six from LC to CC. CONCLUSION: This study has found that patients can show histological features consistent with both CC and LC over time. These patients could represent a subgroup with a true conversion between two separate entities. Alternatively, MC could be a spectral disease where the varying histological features are manifestations of the natural fluctuation. A third possibility could be that the histological changes reflect different manifestations during the disease course and consequently, the diagnostic criteria could be too vague.

An epidemiological study of collagenous colitis in southern Sweden from 2001-2010.

AIM: To estimate the incidence of collagenous colitis (CC) in southern Sweden during 2001-2010. METHODS: Cases were identified by searching for CC in the diagnostic registers at the Pathology Departments in the county of Skåne. The catchment area comprised the south-west part of the county (394 307 inhabitants in 2010) and is a mixed urban and rural type with limited migration. CC patients that had undergone colonoscopy during the defined period and were living in this area were included in the study regardless of where in Skåne they had been diagnosed. Medical records were scrutinized and uncertain cases were reassessed to ensure that only newly diagnosed CC cases were included. The diagnosis of CC was based on both clinical and histopathological criteria. The clinical criterion was non-bloody watery diarrhoea. The histopathological criteria were a chronic inflammatory infiltrate in the lamina propria, a thickened subepithelial collagen layer ≥ 10 micrometers (µm) and epithelial damage such as flattening and detachment. RESULTS: During the ten year period from 2001-2010, 198 CC patients in the south-west part of the county of Skåne in southern Sweden were newly diagnosed. Of these, 146 were women and 52 were men, i.e., a female: male ratio of 2.8:1. The median age at diagnosis was 71 years (range 28-95/inter-quartile range 59-81); for women median age was 71 (range 28-95) years and was 73 (range 48-92) years for men. The mean annual incidence was 5.4/10(5) inhabitants. During the time periods 2001-2005 and 2006-2010, the mean annual incidence rates were 5.4/10(5) for both periods [95% confidence interval (CI): 4.3-6.5 in 2001-2005 and 4.4-6.4 in 2006-2010, respectively, and 4.7-6.2 for the whole period]. Although the incidence varied over the years (minimum 3.7 to maximum 6.7/10(5)) no increase or decrease in the incidence could be identified. The odds ratio (OR) for CC in women compared to men was estimated to be 2.8 (95% CI: 2.0-3.7). The OR for women 65 years of age or above compared to below 65 years of age was 6.9 (95% CI: 5.0-9.7), and for women 65 years of age or above compared to the whole group the OR was 4.7 (95% CI: 3.6-6.0). The OR for age in general, i.e., above or 65 years of age compared to those younger than 65 was 8.3 (95% CI: 6.2-11.1). During the last decade incidence figures for CC have also been reported from Calgary, Canada during 2002-2004 (4.6/10(5)) and from Terrassa, Spain during 2004-2008 (2.6/10(5)). Our incidence figures from southern Sweden during 2001-2010 (5.4/10(5)) as well as the incidence figures presented in the studies during the 1990s (Terrassa, Spain during 1993-1997 (2.3/10(5)), Olmsted, United States during 1985-2001 (3.1/10(5)), Örebro, Sweden during 1993-1998 (4.9/10(5)), and Iceland during 1995-1999 (5.2/10(5)) are all in line with a north-south gradient, something that has been suggested before both for CC and inflammatory bowel disease. CONCLUSION: The observed incidence of CC is comparable with previous reports from northern Europe and America. The incidence is stable but the female: male ratio seems to be decreasing.

What characterizes life story memories? A diary study of freshmen's first term.

We investigated whether memories are selected for the life story based on event characteristics. Sixty-one students completed weekly diaries over their first term at university. They described, dated and rated two events each week. Three months after the end of the term they completed an unexpected memory test. They recalled three memories from the diary period that were important to their life story. Three randomly selected events scoring low on importance to the life story functioned as control memories. Life story memories were rated higher on goal relevance, emotional intensity, importance and rehearsal in the diary and maintained their higher ratings at the test session, while ratings for control memories dropped off. Life story memories' content was less consistent over time but they were more accurately dated than control memories. The results suggest that event characteristics play an important role for the selection of life story memories.

Rumination is associated with the phenomenal characteristics of autobiographical memories and future scenarios.

In the present studies it was investigated whether rumination was associated with the phenomenal characteristics of autobiographical memories and future scenarios. In three studies student participants completed questionnaires on rumination and recalled and rated a positive and a negative memory. In Studies 2 and 3 participants also generated and rated a positive and a negative future scenario. Memories were rated on reliving and emotional valence; future scenarios were rated on reliving, emotional valence, and how probable the scenario was. Generally, the results showed that a higher degree of rumination was related to more reliving of negative memories and future scenarios as well as more negative expectations for the future scenarios. These processes may help explain why rumination predicts depression and other types of negative affect.