Oligodendrocyte gene expression is reduced by and influences effects of chronic social stress in mice.

Oligodendrocyte gene expression is downregulated in stress-related neuropsychiatric disorders, including depression. In mice, chronic social stress (CSS) leads to depression-relevant changes in brain and emotional behavior, and the present study shows the involvement of oligodendrocytes in this model. In C57BL/6 (BL/6) mice, RNA-sequencing (RNA-Seq) was conducted with prefrontal cortex, amygdala and hippocampus from CSS and controls; a gene enrichment database for neurons, astrocytes and oligodendrocytes was used to identify cell origin of deregulated genes, and cell deconvolution was applied. To assess the potential causal contribution of reduced oligodendrocyte gene expression to CSS effects, mice heterozygous for the oligodendrocyte gene cyclic nucleotide phosphodiesterase (Cnp1) on a BL/6 background were studied; a 2 genotype (wildtype, Cnp1+/- ) × 2 environment (control, CSS) design was used to investigate effects on emotional behavior and amygdala microglia. In BL/6 mice, in prefrontal cortex and amygdala tissue comprising gray and white matter, CSS downregulated expression of multiple oligodendroycte genes encoding myelin and myelin-axon-integrity proteins, and cell deconvolution identified a lower proportion of oligodendrocytes in amygdala. Quantification of oligodendrocyte proteins in amygdala gray matter did not yield evidence for reduced translation, suggesting that CSS impacts primarily on white matter oligodendrocytes or the myelin transcriptome. In Cnp1 mice, social interaction was reduced by CSS in Cnp1+/- mice specifically; using ionized calcium-binding adaptor molecule 1 (IBA1) expression, microglia activity was increased additively by Cnp1+/- and CSS in amygdala gray and white matter. This study provides back-translational evidence that oligodendrocyte changes are relevant to the pathophysiology and potentially the treatment of stress-related neuropsychiatric disorders.

Inter-observer agreement of ultrasonographic measurement of alpha and beta angles and the final type classification based on the Graf method.

BACKGROUND: The aim of our study was to investigate the agreement of the assessment of hip ultrasonograms by different observers. METHODS: In the period from June 3rd to December 9th 2002, four different (by experience and field) groups of observers rated all first time sonograms obtained in our hospital. The results in terms of angle and type classification were compared. RESULTS: 158 ultrasonographic images were evaluated. The inter-observer agreement for the classification "normal" (type I) versus "abnormal" (types IIa+ to IV) varied from 83% to 90% with kappa coefficients which indicated moderate (kappa 0.55) to substantial (kappa 0.71) inter-observer agreement. For one pair of observers, a better agreement could be demonstrated for the assessment of immature hips than for mature ones. The deviation for the a-angle was 0 to 16 degrees with a standard deviation of 3.15 degrees (95% CI 2.95, 3.37), and for the b-angle 0 to 26 degrees with a standard deviation of 6.1 degrees (95% CI 5.7, 6.5). The intra-class correlation coefficient was estimated to be 0.72 and 0.34 for the alpha and beta angles respectively. If the hip was immature there was no increase in the discrepancy in assessment between observers. The least agreement existed between the less experienced and the most experienced. It has not been possible to make a statement on the discrepancy with regard to initial signs of instability or decentralization of the hip joints because of the small number of hips of this type. CONCLUSIONS: Although the spread in measured a- and b-angles is large, the inter-observer agreement for the classification showed good results. No disagreement occurred in the diagnosis of normal vs. dysplastic hips, so no severe cases have been missed. The experience and training of the investigators seemed to play an important role with regard to variability and agreement. The agreement in the assessment of immature hips was better than that of mature hips. Therefore, ultrasound examination of infant hips would appear to be a trustworthy screening method.