Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson''s correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.     

Erratum: Rhinitis in children less than 6 years of age: current knowledge and challenges

[This corrects the article on p. 115 in vol. 1, PMID: 22053307.].     

A Comparison of Rice Bran,Wheat Bran and Cellulose as Sources of Dietary Fibrein the Rat

In order to investigate the possible role of fiber in the etiology of acute appendicitis, 203 consecutive appendectomized children with histologically proved appendicitis and 1922 controls were studied by the diet history method. Statistics were performed by multivariate analysis of variance, discriminant analysis and χ². Appendectomized children had statistically significant lower mean daily intake of fiber (17.4 g versus 20.4 g, P < 0.001) including all fiber fractions: cellulose, uronic acid, pentose, exose and lignin. No statistical difference was found for energy, protein, carbohydrate and fat intake. Discriminant analysis proved that only cellulose and exose are independently correlated to appendicitis and lower fiber intake is thought to be the cause in 70% of the cases. Recurrent abdominal pain, chronic constipation and positive family history of appendectomy were more frequent in appendectomized children (P < 0.001). This study gives evidence that low fiber intake could play an important role in the pathogenesis of appendicitis.     

Lack of Alterations in Thyroid Hormones Following Exposure to Polybrominated Diphenyl Ether 47 during a Period of Rapid Brain Development in Mice

Thyroid alterations have been shown to occur following exposure to polybrominated diphenyl ether (PBDE) mixtures, possibly indicating that disruptions in thyroid hormone levels may underlie behavior deficits observed in animals following postnatal PBDE exposure. This study determined whether acute postnatal exposure to PBDE-47 would alter thyroid hormones. Mice were dosed with PBDE-47 on postnatal day 10, and serum collected either 1, 5, or 10 days after the dose. No effect was observed on thyroxine and triiodothyronine levels at any age examined. This suggests that the neurological abnormalities reported in mice exposed to PBDE-47 are not due to acute changes in circulating thyroid hormones at these observed periods.     

Reactions to Teasing in Social Anxiety

The combination of challenge and humor inherent in teasing creates an ambiguous situation that can either increase bonding or create tension in a relationship, depending on how the teasing is interpreted. Although it is well established that individuals with social anxiety interpret ambiguous social situations negatively, no research has examined how individuals with social anxiety react to and interpret teasing. Ninety undergraduate students with high (n = 56) and low (n = 34) levels of social anxiety read vignettes depicting teasing scenarios, and rated how they would feel and behave in the situations. Participants also completed a self-report measure of recalled childhood teasing. Compared to the low social anxiety group, participants in the high social anxiety group reported that they would experience more negative affect in response to the teasing scenarios, and interpreted the teasing scenarios as more malicious and mean-spirited. As well, participants in the high social anxiety group reported being more likely to change the behavior that was the focus of teasing (e.g., changing the way they dress if the focus of teasing was their outfits) compared to participants in the low social anxiety group. Recalled childhood teasing partially mediated group differences on negative affect and behavior change in response to the teasing scenarios. The present results are consistent with the information processing bias literature and have implications for the social functioning of individuals with high levels of social anxiety.