Modeling the natural history of Pelizaeus-Merzbacher disease.

Major gaps in our understanding of the leukodystrophies result from their rarity and the lack of tissue for the interdisciplinary studies required to extend our knowledge of the pathophysiology of the diseases. This study details the natural evolution of changes in the CNS of the shaking pup (shp), a model of the classical form of the X-linked disorder Pelizaeus-Merzbacher disease, in particular in glia, myelin, and axons, which is likely representative of what occurs over time in the human disease. The mutation in the proteolipid protein gene, PLP1, leads to a delay in differentiation, increased cell death, and a marked distension of the rough endoplasmic reticulum in oligodendrocytes. However, over time, more oligodendrocytes differentiate and survive in the spinal cord leading to an almost total recovery of myelination, In contrast, the brain remains persistently hypomyelinated. These data suggest that shp oligodendrocytes may be more functional than previously realized and that their early recruitment could have therapeutic value.

Myelin loss does not lead to axonal degeneration in a long-lived model of chronic demyelination.

Current dogma suggests that chronically demyelinated axons are at risk for degeneration, with axonal loss resulting in permanent disability in myelin disease. However, the trophic role of the myelin sheath in long-term axonal survival is incompletely understood. Previous observations of the effect of dysmyelination or demyelination on axonal survival in the myelin mutants has been limited because of their short life span. In this study, we used the Long-Evans shaker (les) rat, which can live up to 9 months, to study axonal health and survival after chronic demyelination. At 2 weeks, ∼29% of medium and ∼47% of large fiber axons are myelinated in les spinal cord. However, by 3 months, no medium and ∼<1% of large-diameter axons retain myelin. After demyelination, axons have a reduced-caliber, abnormal neurofilament distribution and an increase in mitochondrial number. However, there are no signs of axonal degeneration in les rats up to 9 months. Instead, there is a profound increase in oligodendrocytes, which were found to express BDNF, NT-3, and IGF-1. Importantly, this study provides in vivo evidence that mature glial cells produce various neurotrophic factors that may aid in the survival of axons after chronic demyelination.

Nonmarital Childbearing, Union History, and Women's Health at Midlife.

Despite high rates of nonmarital childbearing in the U.S., little is known about the health of women who have nonmarital births. We use data from the NLSY79 to examine differences in age 40 self-assessed health between women who had a premarital birth and those whose first birth occurred within marriage. We then differentiate women with a premarital first birth according to their subsequent union histories and estimate the effect of marrying or cohabiting versus remaining never-married on midlife self-assessed health, paying particular attention to the paternity status of the mother's partner and the stability of marital unions. To partially address selection bias, we employ multivariate propensity score techniques. Results suggest that premarital childbearing is negatively associated with midlife health for white and black (but not Hispanic) women. We find no evidence that these negative health consequences of nonmarital childbearing are mitigated by either marriage or cohabitation for black women. For other women, only enduring marriage to the biological father is associated with better health than remaining unpartnered.

Development of a Multiplex PCR and Magnetic DNA Capture Assay for Detecting Six Species Pathogens of the Genera Anaplasma and Ehrlichia in Canine, Bovine, Caprine and Ovine Blood Samples from Grenada, West Indies.

Infections with tick-borne pathogens belonging to Anaplasma/Ehrlichia in various vertebrate hosts are a persistent problem resulting in nonspecific clinical signs during early infection. Diagnosis of single and multi-infections with these pathogens, causing diseases in companion/agricultural animals and people, remains a challenge. Traditional methods of diagnosis, such as microscopy and serology, have low sensitivity and specificity. Polymerase chain reaction (PCR) assays are widely used to detect early-phase infections, since these have high sensitivity and specificity. We report the development and validation of an assay involving PCR followed by magnetic capture method using species-specific oligonucleotides to detect six Anaplasma/Ehrlichia species pathogens in canine, bovine, caprine, and ovine blood samples. Overall, the assay application to 455 samples detected 30.1% (137/455) positives for one or more out of six screened pathogens. Single-pathogen infections were observed in 94.9% (130/137) of the positive samples, while co-infections were detected in 5.1% (7/137). Anaplasma marginale infection in cattle had the highest detection rate (34.4%), followed by canines positive for Anaplasma platys (16.4%) and Ehrlichia canis (13.9%). The assay aided in documenting the first molecular evidence for A. marginale in cattle and small ruminants and Ehrlichia chaffeensis and Ehrlichia ewingii in dogs in the Caribbean island of Grenada.

Racial disparities in health among nonpoor African Americans and Hispanics: The role of acute and chronic discrimination.

Racial disparities in health tend to be more pronounced at the upper ends of the socioeconomic (SES) spectrum. Despite having access to above average social and economic resources, nonpoor African Americans and Latinos report significantly worse health compared to nonpoor Whites. We combine data from the parents and children of the 1979 National Longitudinal Survey of Youth (NLSY79) to address two specific research aims. First, we generate longitudinal SES trajectories over a 33-year period to estimate the extent to which socioeconomic mobility is associated with exposure to discrimination (acute and chronic) across different racial/ethnic groups (nonHispanic Whites, nonHispanic Blacks, and Hispanics). Then we determine if the disparate relationship between SES and self-rated health across these groups can be accounted for by more frequent exposure to unfair treatment. For Whites, moderate income gains over time result in significantly less exposure to both acute and chronic discrimination. Upwardly mobile African Americans and Hispanics, however, were significantly more likely to experience acute and chronic discrimination, respectively, than their socioeconomically stable counterparts. We also find that differential exposure to unfair treatment explains a substantial proportion of the Black/White, but not the Hispanic/White, gap in self-rated health among this nationally representative sample of upwardly mobile young adults. The current study adds to the debate that the shape of the SES/health gradient differs, in important ways, across race and provides empirical support for the diminishing health returns hypothesis for racial/ethnic minorities.

Friendships and early relationships: links to sexual initiation among American adolescents born to young mothers.

CONTEXT: Preadolescent friendships and early teenage dating relationships have implications for adolescent sexual initiation that may differ by race and gender. METHODS: Data on participants in the National Longitudinal Survey of Youth and their children are used to profile friendship and dating patterns among a sample of youth born to relatively young mothers. Logistic regression analyses examine whether these patterns predict early sexual initiation, and whether there are differences associated with gender and race. RESULTS: As youth moved from late childhood to mid-adolescence, they shifted from having almost exclusively same-sex, same-grade friends to having more relationships with persons who are of the opposite sex and older. By ages 15-16,34% had had sexual intercourse; the proportion was significantly higher among blacks (45%) than among others (31%). Most adolescents reported neither frequent dating nor a steady partner by ages 15-16, although the prevalence of such reports was related to friendship patterns in late childhood. Twelve percent of youth who initiated sex in early adolescence did so outside of a dating relationship. For most subgroups examined, the odds of initiating intercourse during early adolescence were associated with going steady, but not with frequency of dating. CONCLUSIONS: Prior social networking is an important element in predicting early sexual activity. Overall, youth whose mothers gave birth at young ages remain sexually inexperienced into middle adolescence, but certain subgroups are more likely than others to initiate early sexual activity.

Cohabitation Expectations among Young Adults in the United States: Do They Match Behavior?

Cohabitation continues to rise, but there is a lack of knowledge about expectations to cohabit and the linkage between expectations and subsequent cohabitation. We capitalize on a new opportunity to study cohabitation expectations by drawing on the National Longitudinal Study of Youth (NLSY79) main youth and two waves (2008 and 2010) of the NLSY young adult (YA) surveys (n=1,105). We find considerable variation in cohabitation expectations: 39.9% have no expectation of cohabiting in the future and 16.6% report high odds of cohabiting in the next two years. Cohabitation expectations are associated with higher odds of entering a cohabiting relationship, but are not perfectly associated. Only 38% of young adults with certain cohabitation expectations in 2008 entered a cohabiting union by 2010. Further investigation of the mismatch between expectations and behaviors indicates that a substantial minority (30%) who entered a cohabiting union had previously reported no or low expectations, instances of what we term "unplanned cohabitation." Our findings underscore the importance of considering not just behavior, but also individuals' expectations for understanding union formation, and more broadly, family change.

Mothers' union histories and the mental and physical health of adolescents born to unmarried mothers.

As nonmarital childbearing becomes a dominant pathway to family formation, understanding its long-term consequences for children's well-being is increasingly important. Analysis of linked mother-child data from the 1979 National Longitudinal Survey of Youth indicates a negative association of having been born to a never-married mother with adolescent self-assessed health but not with depressive symptoms. We also consider the role of mothers' subsequent union histories in shaping the adolescent health outcomes of youth born to unmarried mothers. With two exceptions, unmarried mothers' subsequent unions appear to have little consequence for the health of their offspring during adolescence. Adolescents whose mothers subsequently married and remained with their biological fathers reported better health, yet adolescents whose mothers continuously cohabited with their biological fathers without subsequent marriage reported worse adolescent mental health compared with adolescents whose mothers remained continually unpartnered.

Examining the effect of maternal sexual communication and adolescents' perceptions of maternal disapproval on adolescent risky sexual involvement.

PURPOSE: To examine the influence of maternal sexual communication during early adolescence on three adolescent sexual risk behaviors (assessed 5-6 years later) in relation to adolescents' perceptions of maternal disapproval of [their] sexual involvement and contraceptive use. METHODS: Using data from waves 1 and 3 of the National Longitudinal Study of Adolescent Health (Add Health), we distinguish between youth who reported being virgins from those who reported having had sex by the time maternal sexual communication was assessed. RESULTS: Frequency of maternal sexual communication has a significant influence on adolescents' lifetime number of sexual partners, but its effect is moderated by adolescents' perceptions of maternal disapproval of contraceptive use. This relationship holds regardless of whether the adolescent was a virgin or not at the time of the communication. When occurring in the context of adolescent-perceived maternal nondisapproval, greater frequency of maternal sexual communication is associated with a higher likelihood of having multiple sexual partners. Greater frequency of maternal sexual communication was also associated with inconsistent condom use and positive sexually transmitted infection diagnosis among adolescents who were sexually experienced at baseline and who perceived maternal disapproval of contraceptive use. CONCLUSIONS: These findings emphasize the need to evaluate the effect of maternal sexual communication on adolescent risky sexual behaviors in relation to the value context of these discussions as well as the sexual status of the adolescent.