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  • 1
    In: Environmental Research, Elsevier BV, Vol. 87, No. 1 ( 2001-09), p. 37-46
    Type of Medium: Online Resource
    ISSN: 0013-9351
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
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    detail.hit.zdb_id: 1467489-0
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  • 2
    In: Brain, Oxford University Press (OUP), Vol. 142, No. 7 ( 2019-07-01), p. 1876-1886
    Abstract: The mismatch repair gene MSH3 has been implicated as a genetic modifier of the CAG·CTG repeat expansion disorders Huntington’s disease and myotonic dystrophy type 1. A recent Huntington’s disease genome-wide association study found rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated with progression in Huntington’s disease. Using Illumina sequencing in Huntington’s disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG·CTG expansion (P = 0.004) and delayed disease onset (P = 0.003) in both Huntington’s disease and myotonic dystrophy type 1, and slower progression (P = 3.86 × 10−7) in Huntington’s disease. RNA-Seq of whole blood in the Huntington’s disease subjects found that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the Huntington’s disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington’s disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion diseases.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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    SSG: 12
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  • 3
    Online Resource
    Online Resource
    American Academy of Pediatrics (AAP) ; 1999
    In:  Pediatrics Vol. 104, No. 3 ( 1999-09-01), p. e28-e28
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 104, No. 3 ( 1999-09-01), p. e28-e28
    Abstract: 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 other possible sources of support. Calls to family or friends to discuss breastfeeding problems were made by 181 mothers (34.7%). Other calls were to the lactation consultant (16.5%), pediatrician (8.8%), obstetrician or midwife (8.2%), breastfeeding support group (5.9%), and birth hospital (2.5%). Factors significantly associated with breastfeeding success were maternal graduate education (OR: 3.20), appraisal of the breastfeeding experience while in the hospital (OR: 1.49), and age (OR: 1.06). When only mothers who had a home nurse visit were included in the model, maternal graduate education (OR: 3.66), appraisal of hospital breastfeeding experience (OR: 1.42), and maternal rating of the home nurse visit (OR: 1.71) were significantly associated with successful breastfeeding. Conclusion. Health system support of breastfeeding women during their hospital stay and early postdischarge period is an important factor in their success. Hospitals should monitor closely the actual quality and quantity of care provided by clinical support personnel and measure their impact on the outcomes on an ongoing basis.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 1999
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  • 4
    In: Movement Disorders, Wiley, Vol. 30, No. 3 ( 2015-03), p. 393-401
    Abstract: Putaminal metabolites examined using cross‐sectional magnetic resonance spectroscopy (MRS) can distinguish pre‐manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty‐four participants (30 controls, 25 pre‐manifest HD, 29 early HD) recruited as part of TRACK‐HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK‐HD motor assessment. Statistical analyses included linear regression and one‐way analysis of variance (ANOVA). At all time‐points N ‐acetyl aspartate and total N ‐acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre‐manifest HD than in controls, whereas the gliosis marker myo‐inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross‐sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD‐affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi‐site assessments in large, pathologically diverse cohorts. © 2015 International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2041249-6
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 1998
    In:  Pediatric Research Vol. 43 ( 1998-4), p. 262-262
    In: Pediatric Research, Springer Science and Business Media LLC, Vol. 43 ( 1998-4), p. 262-262
    Type of Medium: Online Resource
    ISSN: 0031-3998 , 1530-0447
    Language: Unknown
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1998
    detail.hit.zdb_id: 2031217-9
    SSG: 12
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  • 6
    In: JAMA Neurology, American Medical Association (AMA), Vol. 73, No. 1 ( 2016-01-01), p. 102-
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2016
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  • 7
    In: Brain Communications, Oxford University Press (OUP), Vol. 4, No. 6 ( 2022-11-02)
    Abstract: An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3020013-1
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 1998
    In:  Pediatric Research Vol. 43 ( 1998-4), p. 220-220
    In: Pediatric Research, Springer Science and Business Media LLC, Vol. 43 ( 1998-4), p. 220-220
    Type of Medium: Online Resource
    ISSN: 0031-3998 , 1530-0447
    Language: Unknown
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1998
    detail.hit.zdb_id: 2031217-9
    SSG: 12
    Location Call Number Limitation Availability
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