CDHR1 mutations in retinal dystrophies

We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjects. Mutation screening was done using a customized next generation sequencing panel targeting 105 genes implicated in inherited retinal disorders. In one family, homozygosity mapping with subsequent candidate gene analysis was performed. Stringent filtering for rare and potentially disease causing variants following a model of autosomal recessive inheritance led to the identification of eleven different CDHR1 variants in nine index cases. All variants were novel at the time of their identification. In silico analyses confirmed their pathogenic potential. Minigene assays were performed for two non-canonical splice site variants and revealed missplicing for the mutant alleles. Mutations in CDHR1 are a rare cause of retinal dystrophy. Our study further expands the mutational spectrum of this gene and the associated clinical presentation

Differential exposure and reactivity to interpersonal stress predict sex differences in adolescent depression

This study tested the hypothesis that higher rates of depression in adolescent girls are explained by their greater exposure and reactivity to stress in the interpersonal domain in a large sample of 15-year-olds. Findings indicate that adolescent girls experienced higher levels of total and interpersonal episodic stress, whereas boys experienced higher levels of chronic stress (academic and close friendship domains). Higher rates of depression in girls were explained by their greater exposure to total stress, particularly interpersonal episodic stress. Adolescent girls were also more reactive (more likely to become depressed) to both total and interpersonal episodic stress. The findings suggest that girls experience higher levels of episodic stress and are more reactive to these stressors, increasing their likelihood of becoming depressed compared to boys. Results were discussed in terms of girls' greater interpersonal focus and implications for understanding sex differences in depression

Understanding the sex difference in vulnerability to adolescent depression: an examination of child and parent characteristics

This study examined sex differences in risk factors associated with adolescent depression in a large sample of boys and girls. Moderation and mediation explanatory models of the sex difference in likelihood of depression were examined. Findings indicate that the factors associated with depression in adolescent boys and girls are quite similar. All of the variables considered were associated with depression, but sex did not moderate the impact of vulnerability factors on likelihood of depression diagnosis. However, negative self-perceptions in the domains of achievement, global self-worth, and physical appearance partially mediated the relationship between sex and depression. Further, girls had higher levels of positive self-perceptions in interpersonal domains that acted as suppressors and reduced the likelihood of depression in girls. These findings suggest that girls' higher incidence of depression is due in part to their higher levels of negative self-perceptions, whereas positive interpersonal factors serve to protect them from depressive episodes

A Cross-Species Analysis of MicroRNAs in the Developing Avian Face

Higher vertebrates use similar genetic tools to derive very different facial features. This diversity is believed to occur through temporal, spatial and species-specific changes in gene expression within cranial neural crest (NC) cells. These contribute to the facial skeleton and contain species-specific information that drives morphological variation. A few signaling molecules and transcription factors are known to play important roles in these processes, but little is known regarding the role of micro-RNAs (miRNAs). We have identified and compared all miRNAs expressed in cranial NC cells from three avian species (chicken, duck, and quail) before and after species-specific facial distinctions occur. We identified 170 differentially expressed miRNAs. These include thirty-five novel chicken orthologs of previously described miRNAs, and six avian-specific miRNAs. Five of these avian-specific miRNAs are conserved over 120 million years of avian evolution, from ratites to galliforms, and their predicted target mRNAs include many components of Wnt signaling. Previous work indicates that mRNA gene expression in NC cells is relatively static during stages when the beak acquires species-specific morphologies. However, miRNA expression is remarkably dynamic within this timeframe, suggesting that the timing of specific developmental transitions is altered in birds with different beak shapes. We evaluated one miRNA:mRNA target pair and found that the cell cycle regulator p27KIP1 is a likely target of miR-222 in frontonasal NC cells, and that the timing of this interaction correlates with the onset of phenotypic variation. Our comparative genomic approach is the first comprehensive analysis of miRNAs in the developing facial primordial, and in species-specific facial development

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

The Unified Behavioral Health Center for Military Veterans and Their Families

The public-private partnership model embodied in the UBHC is an innovative approach to expanding services for veterans and their families. To foster understanding of the UBHC model and shed light on how it is serving veterans and their families, RAND evaluated the center's activities. The evaluation was intended to document the implementation of a unique public-private collaborative approach for providing care to veterans and their families, in order to assess the approach's viability, identify implementation challenges and successes that the program can learn from, and facilitate its replication in other communities should it prove successful. This report presents the results of RAND's evaluation. The evaluation addressed four questions: * What resources and capacities were available for providing care in the UBHC? * What barriers and facilitators to implementing this model of care did the center encounter? * What services were delivered, and what were the characteristics of the patients who received these services? * How did receiving care affect patients' health outcomes

Cognitive Vulnerability to Depression in Canadian and Chinese Adolescents

The goal of the current study was to compare diathesis-stress and transactional models of cognitive vulnerability to depression in samples of Canadian (n = 118) and Chinese (n = 405) adolescents. We utilized a six-month multi-wave, longitudinal design in order to examine whether (a) perceived control moderated the association between the occurrence of dependent interpersonal stressors and subsequent increases in depressive symptoms (i.e., a diathesis-stress perspective) and (b) dependent interpersonal stressors mediated the association between perceived control and subsequent increases in depressive symptoms (i.e., a transactional perspective). Results from idiographic, time-lagged, hierarchical linear modeling analyses indicated that for Canadian adolescents both diathesis-stress and transactional models were significant predictors of depressive symptomology. When examining the diathesis-stress model, boys, but not girls, who reported lower perceived control, reported higher levels of depressive symptoms following the occurrence of dependent interpersonal stress. Gender differences, however, were not present in the transactional model. In contrast, transactional, but not diathesis-stress, models were significant in Chinese adolescents, and gender differences did not emerge. Overall, these results may reflect culturally-relevant differences in the etiology of depression in Canadian and Chinese adolescents