Evaluation of hypoglycemic effect, safety and immunomodulation of Prevotella copri in mice.

The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes. In this study the hypoglycemic effect of live P. copri was confirmed in mice and pasteurization of P. copri was shown to further enhance its capacity to improve glucose tolerance. The safety of live and pasteurized P. copri was evaluated by a 29-day oral toxicity study in mice. P. copri did not induce any adverse effects on body growth. General examination of the mice, gross pathological and histological analysis showed no abnormalities of the vital organs. Though relative liver weights were lower in the pasteurized (4.574 g ± 0.096) and live (4.347 g ± 0.197) P. copri fed groups than in the control mice (5.005 g ± 0.103) (p = 0.0441 and p = 0.0147 respectively), no liver biochemical marker aberrations were detected. Creatinine serum levels were significantly lower in mice fed with live (p = 0.001) but not pasteurized (p = 0.163) P. copri compared to those of control mice. Haematological parameter analysis and low plasma Lipopolysaccharide Binding Protein (LBP) levels ruled out systemic infection and inflammation. Immunomodulation capacity by P. copri as determined by blood plasma cytokine analysis was limited and gut colonisation occurred in only one of the 10 mice tested. Taken together, no major adverse effects were detected in P. copri treated groups compared to controls.

Determinants of outcome of vocational rehabilitation.

BACKGROUND: Information regarding the determinants of successful vocational rehabilitation (VR) is scarce. OBJECTIVE: Investigate whether sex, duration, quality of life and financial circumstances influence the success of VR. METHODS: The study group consisted of 519 participants (293 women, 56%), who finished VR in the period 2000-2014. The group was divided into the following subgroups: dropouts, unsuccessful and successful VR. Data were collected by questionnaire. RESULTS: Income had the most impact on whether the outcome was successful. Having supplemental income when entering the VR program increased the likelihood of a successful conclusion, odds ratio (OR) 5.60 (95% CI; 2.43-13.59) (p < 0.001), being on sick leave OR 5.02 (95% CI 1.93-13.79) (p < 0.001) or rehabilitation pension OR 1.93 (95% CI 1.07-3.52) (p < 0.03). The participants in the successful sub-group were older (p < 0.06) and stayed in rehabilitation longer (p < 0.001), compared to those who were unsuccessful. However, the effect on OR was limited: 1.03 (95% CI 1.01-1.06) and 1.04 (95% CI 1.02-1.07), respectively. CONCLUSIONS: For this sample, supplemental income appears to be the most important factor for a successful rehabilitation outcome. Checking financial status at the beginning of the rehabilitation process could minimize financial strain and increase the likelihood of success.

Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q.

OBJECTIVE: To localize genes conferring susceptibility to bipolar affective disorder. METHODS: Seven families were selected on the basis of containing multiple cases of bipolar affective disorder present in three or more generations, an absence of schizophrenia and unilineal transmission. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10 cM intervals across the whole genome. All markers were subjected to initial two-point and three-point analyses using LOD score and model-free analysis. All regions producing a result significant at P<0.01 were then subjected to four-point LOD score analysis under the assumption of heterogeneity. RESULTSA four-point LOD score of 2.8 was obtained using a dominant model and including unipolar cases as affected in the region of D12S342. Four-point LOD scores of 2 were obtained around D1S243, D1S251 and D3S1265. The positive results around D1S243 were accounted for by a LOD score of 3.1 occurring in a single pedigree. CONCLUSIONS: Since there has been previous strong support for linkage to the region of 12q23-q24 around D12S342, it now seems very probable that it does indeed contain a gene influencing susceptibility to bipolar affective disorder. Some evidence for linkage in the region of 1q near to D1S251 has been reported in one previous study. It therefore seems that this region of 1q and the region of 1p close to D1S243 may also harbour susceptibility genes.

Neuregulin 1 and susceptibility to schizophrenia.

The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.