White matter predicts functional connectivity in premanifest Huntington's disease.

OBJECTIVES: The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. METHODS: Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. RESULTS: We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. INTERPRETATION: Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero-posterior dissociation that is in keeping with the caudo-rostral gradient of striatal pathology in HD.

Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease.

OBJECTIVES: To evaluate in vivo brain metabolite differences in control subjects, individuals with premanifest Huntington disease (pre-HD), and individuals with early HD using ¹H magnetic resonance spectroscopy (MRS) and to assess their relationship with motor performance. METHODS: Eighty-five participants (30 controls, 25 pre-HD, and 30 early HD) were recruited as part of the TRACK-HD study. Eighty-four were scanned at 3 T with single-voxel spectroscopy in the left putamen. Disease burden score was >220 among pre-HD individuals. Subjects underwent TRACK-HD motor assessment including Unified Huntington's Disease Rating Scale (UHDRS) motor scoring and a novel quantitative motor battery. Statistical analyses included linear regression and one-way analysis of variance. RESULTS: Total N-acetylaspartate (tNAA), a neuronal integrity marker, was lower in early HD (∼15%) vs controls (p < 0.001). N-acetylaspartate (NAA), a constituent of tNAA, was lower in pre-HD (∼8%) and early HD (∼17%) vs controls (p < 0.05). The glial cell marker, myo-inositol (mI), was 50% higher in early HD vs pre-HD (p < 0.01). In early HD, mI correlated with UHDRS motor score (R² = 0.23, p < 0.05). Across pre-HD and early HD, tNAA correlated with performance on a tongue pressure task (R² = 0.30, p < 0.0001) and with disease burden score (R² = 0.17, p < 0.005). CONCLUSIONS: We demonstrate lower putaminal tNAA in early HD compared to controls in a cross-section of subjects. A novel biomarker role for mI in early HD was also identified. These findings resolve disagreement in the literature about the role of MRS as an HD biomarker. We conclude that putaminal MRS measurements of NAA and mI are promising potential biomarkers of HD onset and progression.

Managing genetic discrimination: strategies used by individuals found to have the Huntington disease mutation.

The introduction of predictive testing for Huntington disease (HD) over 20 years ago has led to the advent of a new group of individuals found to have the HD mutation that are currently asymptomatic, yet destined in all likelihood to become affected at some point in the future. Genetic discrimination, a social risk associated with predictive testing, is the differential treatment of individuals based on genotypic difference rather than physical characteristics. While evidence for genetic discrimination exists, little is known about how individuals found to have the HD mutation cope with the potential for or experiences of genetic discrimination. The purpose of this study was to explore how individuals found to have the HD mutation manage the risk and experience of genetic discrimination. Semi-structured individual interviews were conducted with 37 individuals who were found to have the HD mutation and analysed using grounded theory methods. The findings suggest four main strategies: "keeping low", minimizing, pre-empting and confronting genetic discrimination. Strategies varied depending on individuals' level of engagement with genetic discrimination and the nature of the experience (actual experience of genetic discrimination or concern for its potential). This exploratory framework may explain the variation in approaches and reactions to genetic discrimination among individuals living with an increased risk for HD and may offer insight for persons at risk for other late-onset genetic diseases to cope with genetic discrimination.

A side-by-side comparison of sampling methods for settled, indoor allergens.

Exposure to indoor allergens is associated with asthma, but there is no standardized sampling method for measuring allergens. We compared the association of measured allergen exposure and serum-specific IgE levels and the precision of three sampling methods (Cyclone, Mighty Mite, and Readivac II) to identify a standardized sampling method for indoor allergens. A random sample of 72 children, 5 to 17 years old, with doctor-diagnosed asthma who lived in the same residence >or=2 years were enrolled. Composite, side by side floor samples were obtained with all three methods. Dust allergen concentrations and serum-specific IgE levels were measured for Der f I, Fel d I, and Bla g I. Mean allergen concentration did not differ significantly by sampling method. Cat allergen was significantly correlated with serum-specific IgE for Cyclone (P=0.003) and Mighty Mite (P=0.008), but only marginally for Readivac II (P=0.07). Dust mite allergen was significantly correlated with serum-specific IgE for Readivac II (P=0.02) and Cyclone (P=0.038), but not for Mighty Mite (P=0.12). Cockroach allergen was not correlated with serum-specific IgE for any sampling method. In multiple linear regression, cat allergen was associated with serum-specific IgE for Cyclone (P=0.007) and Mighty Mite (P=0.02), but not for Readivac II (P=0.06). In contrast, dust mite allergen was marginally associated with serum-specific IgE for Readivac II (P=0.07), but not for Mighty Mite (P=0.64) or Cyclone (P=0.27). The Cyclone and Mighty Mite were more precise than Readivac II for cat allergen, but there was no difference for dust mite allergen (P>0.05). No single method is superior for measurement of indoor allergens. In general, cat allergen collected with the Cyclone was a better predictor of serum-specific IgE levels to Fel d I, whereas dust mite allergen collected with the Readivac II was a better predictor of serum-specific IgE levels to Der f I.

Health system factors contributing to breastfeeding success.

OBJECTIVE: To identify and characterize health care system factors that contribute to successful breastfeeding in the early postpartum period. STUDY DESIGN: A prospective 8-week cohort study of 522 women at five area hospitals who had a vaginal delivery of a healthy, full-term single child and who intended to breastfeed. Mothers and infants had free access to each other for breastfeeding during the hospital stay. Data were obtained through chart review and surveys. In-person postpartum interviews in the hospital and 4- and 8-week telephone interviews were used to determine participants' perceptions of breastfeeding support by hospital personnel, home visit nurses, and family and friends. The hospital in-person interview with each mother was conducted before discharge to confirm maternal interest and intent to breastfeed. Questions were asked regarding breastfeeding information and support provided by medical and nursing personnel. Mothers were asked to rate the quality of information, as well as the degree of support they received for breastfeeding. Mothers also were asked to rate their hospital breastfeeding experience. A second interview was conducted by telephone 4 weeks after birth. The focus of this interview was to ascertain the rating of their breastfeeding experience, the quality of their interactions with health care professionals, and whether supplemental formula was being provided to the infant. If supplemental formula was being provided, the mothers were asked to quantify the volume and frequency of supplementation. A final telephone interview was conducted when the infants were 8 weeks of age. This interview determined the continuance or cessation of breastfeeding and information about formula supplementation, as in the 4-week interview. Mothers were given a journal and asked to note all telephone calls, clinic visits, and home nurse visits that related to breastfeeding issues and concerns. Demographic data examined included maternal age, marital status, highest level of education reached, race, employment, insurance coverage, and length of stay in the hospital. Pregnancy characteristics included prenatal care, parity, and gravity. Infant characteristics included gestational age and birth weight. Other factors examined included maternal rating of the support received from the infant's father for the decision to breastfeed, the time the infant spent in the mother's hospital room, and whether the infant was breastfed in the delivery room. RESULTS: The women were mostly white (90%), educated (82% had some college education), married, older (mean maternal age of 29.3 years), and insured (92% commercial). The primary outcome of interest was success at breastfeeding. Success was determined based on each mother's initial estimate of the planned duration of breastfeeding. Of the participants, 76% breastfed successfully for at least as long as they had initially planned. Seventeen percent of the mothers had stopped breastfeeding at the time of the 4-week interview, and 29% had stopped by the 8-week interview. Of the infants' fathers, 97% were reported by the mothers to be supportive of the decision to breastfeed. Once discharged, 98% of mothers expected to have help with the household chores. Eighty percent rated their hospital breastfeeding experience as good or very good. However, only 56% rated hospital breastfeeding support as good or very good, and only 44% spoke with a lactation consultant while in the hospital. Of those who spoke with the lactation consultant, 85% felt more confident afterward. Hospital nurses talked with 82% of women, and 97% of these found this helpful. Seventy-four percent reported receiving a home nursing visit after discharge, and of these, 82% found it helpful. Successful mothers were significantly more likely to report that the visiting nurse watched them breastfeed and asked how it was going. Mothers were more likely to call or visit family and friends with concerns about breastfeeding than

Effect of floor type and energy source on growth and productivity of broiler breeders.

Arbor Acres broiler breeder chicks were raised through an egg production cycle on either wood or plastic slats and either full- or partial-slat flooring. Two diets with either corn starch (CHO) or fat (FAT) as the primary energy source were fed at a rate consistent with the breeder's recommendations to examine the effect of energy source on fat deposition and productivity. Fertility and hatchability were unaffected by slat material or floor type. Mean hen-day egg production and floor egg production were significantly (P less than .05) reduced for birds on full-slat floors. In addition, birds on full-slat, plastic floors averaged 6.4% fewer eggs over the production cycle versus birds on full-slat, wood floors. Floor egg recovery from full-slat floors was not considered to be the major reason for this reduced egg production. Wood or plastic slats had no effect on average egg production for birds on partial-slat and litter floors. Energy source had no effect on growth or productivity except during Weeks 17 and 18 of production when birds fed the FAT diet had a greater egg production than birds fed the CHO diet. Overall mean hen-day egg production, fertility, and hatchability were unaffected by dietary energy source. Abdominal fat pad weight and adipocyte characteristics were also similar for FAT- and CHO-fed birds.