Recovery and economy; salary and allowances: a 10-year follow-up of income for persons diagnosed with first-time psychosis

Social Psychiatry and Psychiatric Epidemiology - Persons with severe mental health problems (SMHP) point out financial strain as one of their main problems. De-institutionalisation in welfare...     

High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

Background:

Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m⁻²) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer.

Patients and methods:

In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up.

Results:

High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact.

Conclusion:

High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied.     

Liposomal delivery system enhances anti-inflammatory properties of curcumin

Curcumin is a well-established natural antioxidant and anti-inflammatory agent. Up till now its potential in treatment of vaginal inflammation has not been evaluated. We are aiming at developing liposomal delivery system for curcumin targeting vaginal administration. Liposomes as nanosized phospholipid-based vesicles are expected to solubilize curcumin and enhance its activity, thus serving as an advanced topical formulation in the treatment of vaginal inflammation. Curcumin and curcuminoids were analyzed by the high-performance liquid chromatography method. Liposomes containing curcumin/curcuminoids of various sizes were prepared and characterized. Antioxidant activities of curcumin and liposomal curcumin were compared based on 1,1-diphenyl-2-picrylhydrazyl radical scavenging and superoxide dismutase activities. The anti-inflammatory activities were determined by measuring the inhibition of lipopolysaccharide -induced nitric oxide, interleukin-1β, and tumor necrosis factor-α production in macrophage RAW 264.7 cells. Curcumin/curcuminoids were encapsulated in phosphatidylcholine vesicles with high yields. Vesicles in the size range around 200 nm were selected for stability and cell experiments. Liposomal curcumin were found to be twofold to sixfold more potent than corresponding curcuminoids. Moreover, the mixture of curcuminoids was found to be more potent than pure curcumin in regard to the antioxidant and anti-inflammatory activities. Liposomal delivery systems for curcumin are promising formulations for the treatment of vaginal inflammation.     

No association between a common single nucleotide polymorphism,rs4141463, in the MACROD2 gene and autism spectrum disorder

The Autism Genome Project (AGP) Consortium recently reported genome‐wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case–control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non‐centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case–control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta‐analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944–1.133), with a P‐value of 0.5 for ASD and OR of 0.99 (95% CI 0.88–1.11) with P‐value = 0.85 for the Autism (A) sub‐group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. © 2011 Wiley‐Liss, Inc.     

Activation of proteinase-activated receptor-2 by human kallikrein-related peptidases

Proteinase-activated receptor-2 (PAR2) is a seven transmembrane spanning, G-protein-coupled receptor, present on the membrane of many cell types including keratinocytes. In skin, PAR2 is suggested to play a regulatory role during inflammation, epidermal barrier function, and pruritus. PAR2 is activated by trypsin-like proteases by a unique mechanism where cleavage of the receptor leads to the release of a small peptide, which activates the receptor as a tethered ligand. The endogenous activators of PAR2 on keratinocytes have not been identified as of yet. Potential candidates are kallikrein-related peptidases (KLKs) expressed by epidermal cells. Therefore, the ability of four human skin-derived KLKs was examined with regard to their capacity to activate PAR2 in vitro. PAR2 cleavage was followed by immunofluorescence analysis and functional activation by measurements of changes in intracellular calcium levels. We found that KLK5 and KLK14, but neither KLK7 nor KLK8, induced PAR2 signalling. We conclude that certain, but not all, epidermal KLKs are capable of activating PAR2. We could also show the coexpression of KLK14 and PAR2 receptor in inflammatory skin disorders. These in vitro results suggest that KLKs may take part in PAR2 activation in the epidermis and thereby in PAR2-mediated inflammatory responses, including epidermal barrier repair and pruritus. The role of KLKs in PAR2 activation in vivo remains to be elucidated.     

Even more suicide attempts in clinical trials with paroxetine randomised against placebo

Background

Following our previous publication we have received critical comments to our conclusions as well as new data that are strengthening our findings.

Results

With the new data, 11 suicide attempts among patients on paroxetine against 1 among patients on placebo, we found with a Bayesian technique that the posterior probability that medication with paroxetine is associated with an increased intensity per year of a suicide attempt is from 0.98 to 0.99, depending on the prior. We found that the comment to our article by GSK representatives contained errors, misunderstanding and unwillingness to accept Bayesian principles in the analysis of clinical trials.

Conclusion

We were in our previous publication, with preliminary data and a Bayesian approach, able to raise a concern that suicide attempts might be connected with the use of paroxetine. This suspicion has now been confirmed.     

Genetics of psoriasis in Iceland: evidence for linkage of subphenotypes to distinct Loci

Psoriasis is a chronic inflammatory skin disease with overlapping subphenotypes. It has a strong complex genetic component, but has been problematic to identifying significant loci. We evaluated 1000 patients with chronic plaque psoriasis and documented several subphenotypes. Here we report results of genome-wide linkage scans for psoriasis genes in 238 Icelandic families with 874 patients. MHC linkage was confirmed with LOD score of 10.9. When the entire cohort was analyzed, two other loci with LOD scores of 2.5 and 1.5 were observed on 16q and 4q, respectively. Stratification into subphenotypes revealed additional loci with LOD scores exceeding or approaching significance. A LOD score of 5.7 appeared on 16q in PsA patients with analysis conditioned on parental inheritance. A LOD score of 3.6 on 4q was detected when disease occurred at or older than 17 y, our median cohort age. This locus was defined by a marker near one reportedly displaying significant linkage in a Chinese psoriasis population and near suggestive linkage in a Caucasian population. A LOD of 3.0 was observed on 10q when disease onset occurred in the scalp. Furthermore, clinical stratification either revealed or increased LOD scores when compared to unstratified analysis and some coincided with previous reports.