Background: Evidence for effective interventions to prevent long-term sequelae after concussion is sparse. This study aimed to test the efficacy of Get going After concussIoN (GAIN), an interdisciplinary, individuallytailored intervention of 8 weeks duration based on gradual return to activities and principles from cognitive behavioural therapy. Methods: We conducted an open-label, parallel-group randomised trial in a hospital setting in Central Denmark Region. Participants were 15À30-year-old patients with high levels of post-concussion symptoms (PCS) 2À6 months post-concussion (i.e., a score 20 on the Rivermead Post-concussion Symptoms Questionnaire (RPQ)). They were randomly assigned (1:1) to either enhanced usual care (EUC) or GAIN+EUC. Masking of participants and therapists was not possible. The primary outcome was change in RPQ-score from baseline to 3-month FU. All analyses were done on an intention-to-treat basis using linear mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT02337101. Findings: Between March 1, 2015, and September 1, 2017, we included 112 patients. Patients allocated to GAIN+EUC (n=57) reported a significantly larger reduction of PCS than patients allocated to EUC (n=55) with a mean adjusted difference in improvement of 7¢6 points (95% confidence interval (CI) 2¢0À13¢1, p=0¢008), Cohen's d=0¢5 (95% CI 0¢1À0¢9). Number needed to treat for prevention of one additional patient with RPQ 20 at 3-month FU was 3¢6 (95% CI 2¢2À11¢3). No adverse events were observed. Interpretation: Compared with EUC, GAIN+EUC was associated with a larger reduction of post-concussion symptoms at 3-month FU. Funding: Central Denmark Region and the foundation "Public Health in Central Denmark Region-a collaboration between municipalities and the region".

Brain imaging in Klinefelter syndrome (47, XXY) (KS), a genetic disorder characterized by the presence of an extra X chromosome, may contribute to understanding the relationship between gene expression, brain structure, and subsequent cognitive disabilities and psychiatric disorders.We conducted the largest to date voxel-based morphometry study of 65 KS subjects and 65 controls matched for age and education and correlated these data to neuropsychological test scores. The KS patients had significantly smaller total brain volume (TBV), total gray matter volume (GMV) and total white matter volume (WMV) compared to controls, whereas no volumetric difference in cerebral spinal fluid (CSF) was found. There were no differences in TBV, GMV, WMV or CSF between testosterone treated KS (T-KS) and untreated KS (U-KS) patients. Compared to controls, KS patients had significantly decreased GMV bilaterally in insula, putamen, caudate, hippocampus, amygdala, temporal pole and frontal inferior orbita. Additionally, the right parahippocampal region and cerebellar volumes were reduced in KS patients. KS patients had significantly larger volumes in right postcentral gyrus, precuneus and parietal regions. Multivariate classification analysis discriminated KS patients from controls with 96.9% (p < 0.001) accuracy. Regression analyses, however, revealed no significant association between GMV differences and cognitive and psychological factors within the KS patients and controls or the groups combined. These results show that although gene dosage effect of having and extra X-chromosome may lead to large scale alterations of brain morphometry and extended cognitive disabilities no simple correspondence links these measures.

Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3-acetic acid. Indoleacetic acid (IAA), 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA were metabolized to different extents by strains 61A24 and 110. Metabolites were isolated and analyzed by high-performance liquid chromatography and conventional mass spectrometry (MS) methods, including MS-mass spectroscopy, UV spectroscopy, and high-performance liquid chromatography-MS. The identified products indicate a novel metabolic pathway in which IAA is metabolized via dioxindole-3-acetic acid, dioxindole, isatin, and 2-aminophenyl glyoxylic acid (isatinic acid) to anthranilic acid, which is further metabolized. Degradation of 4-Cl-IAA apparently stops at the 4-Cl-dioxindole step in contrast to 5-Cl-IAA which is metabolized to 5-Cl-anthranilic acid.Bradyrhizobium japonicum reduces atmospheric nitrogen to ammonia when the bacterium is located in the root nodules of soybean (Glycine max) plants. The formation of root nodules results from a complex series of interactions between the bacterium and the plant and requires the growth and differentiation of both partners. Indoleacetic acid (IAA) has long been assumed to play a role in one or more aspects of nodule growth and development (11), although no specific role for IAA in nodule formation or development has been suggested.Bradyrhizobia have the enzymatic capacity to produce IAA in culture (7,8), and it has been demonstrated that nodules induced by an IAA-overproducing B. japonicum strain contain much greater amounts of IAA than nodules induced by the parental strain (5, 6), thus indicating that the bacterium can affect nodule IAA levels.In addition to being capable of IAA synthesis, some strains of B. japonicum are able to catabolize IAA. It was hypothesized that the first enzyme catalyzes an oxygen-consuming opening of the indole structure. A degradation pathway with anthranilic acid as the eventual degradation product was proposed (2). In this paper we report the analysis of the degradation products from IAA, 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA, determined by conventional mass spectrometry (MS) and by high-performance liquid chromatography (HPLC)-thermospray MS. Using these methods, we have identified the intermediates in IAA catabolism in order to compare the degradation products with those of the degradation pathway postulated for B. japonicum (2). MATERIALS AND METHODSStrains and media. B. japonicum strain 110 (4), a derivative of USDA110, and strain 61A24 (14), showing different kinetics of IAA degradation, were used in this study. The strains were grown in yeast broth medium (1) on a rotary shaker with gentle shaking (100 rpm) at 28ЊC until turbidity reached an optical density at 450 nm of 0.35 to 0.45 (3 to 5 days).Preparing cultures for in vivo experiments. IAA was added to a final concentration of 0.2 mM to a stationary liquid culture and incubated overnight to induce IAA-catabolizing enzymes. The following day, the culture was centrifuged at 20,000 ϫ g for 10 min at 4ЊC. The pellet was w...

This study presents psychometric properties of the Danish version of the Sources of Meaning and Meaning in Life Scale (SoMe‐Da) and associations to socio‐demographic and religious characteristics. Participants were 554 Danes, 66% women ranging in age between 15 and 91 years. Exploratory factor analysis (EFA) suggested a five factor structure for the 26 sources if meaning. Construct validity within the SoMe‐Da and between mental health variables were established. Generativity associated most strongly with meaningfulness followed by spirituality, attentiveness, and explicit religiosity. We found religious characteristics to be more strongly associated with meaningfulness than socio‐demographic variables. Finally, we found distinct patterns of preferred sources of meaning between Christians, agnostics, and atheists. Christians and agnostics seemed to be more motivated by self‐transcendance, whereas atheists may be more motivated by self‐actualization. Results indicate that the SoMe‐Da appears to be a valid instrument for measuring the content and degree of personal meaning in life.

Interleukin-8 (IL-8) may play an important role in the development of synovitis in rheumatoid arthritis (RA), in that it is a powerful chemoattractant for neutrophils and T cells. The aim of this study was to examine the distribution of IL-8 in the synovial membrane and cartilage, from RA, osteoarthritis (OA) and normal joints. By immunohistochemical techniques, IL-8 was shown to be present in the lining layer cells in RA (87%) and in OA (62%). By contrast, only a few of the normal synovial lining layer cells (14%) contained IL-8. Deeper in the membrane the number of IL-8 positive cells decreased. Only vessels were highly positive for IL-8. At the RA cartilage-pannus junction 26% of the cells contained IL-8, whereas at the OA cartilage-pannus junction 8% of the cells were IL-8 positive (P < 0.05). Chondrocytes present in joint surface cartilage stained positive for IL-8 in an average of 20% of the cells of both RA and OA. These results provide histological evidence that IL-8 is present in the arthritic synovial tissue and cartilage, and is distributed in a manner that may form a chemotactic gradient, which favours localisation of neutrophils to the joint lumen.