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1.
Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
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Between June and September, 1986, an outbreak of measles occurred in Pilkhi Primary Health Centre area (population 56,000) in Tehri Garhwal district, Uttar Pradesh, India. Overall, 1092 cases were identified and 62 died; case-fatality ratio was 5.7%. Illness was restricted primarily to children below 15 years of age; 38% cases were in children under 5 and 58% between 5-14 years of age. To better characterize the outbreak, a survey was conducted in 13 affected villages. The age of the cases ranged from 5 months to 19 years (median = 7.0 years). The age-specific attack rates were 22.4%, 54.5%, 46.2% and 35.3% for children under 1, 1-4, 5-9, 10-14 years of age respectively. In as many as four villages, the attack rate in children below ten was 80% or more. Secondary attack rate among family members was 70%. Overall, 82% of children with measles developed complications which consisted mainly of pneumonia, diarrhoea and dysentery. The age-specific case-fatality ratios in infants and children 1-4 years of age were 23.1% and 11.5% respectively; thereafter the rates tended to decline with increasing age and was higher in females than in males (less than 0.05). Pneumonia which was a complication in 39% of measles cases contributed to 56% of deaths. Traditional beliefs and customs in the area were strong and did not encourage treatment of measles cases. Although a measles vaccination programme has been launched in India since 1985, only 30 districts could be covered during the first year and another 90 during 1986.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Based on experiments on fresh cadaveric and accidentally amputated 8 upper limbs of children, study of ulnae for presence and absence of non articular strip on the trochlear notch, measurements of carrying angle, length of forearm bones, pronation-supination, height and weight in 2250 infants, children and adults of various age groups and clinical observations on 800 cases of injuries around elbow many new facts have been observed about the development of the carrying angle and its significance in the etiopathogenesis of various types of fractures seen around the elbow. The carrying angle develops in response to pronation of the forearm and is dependent on length of the forearm bones. Lesser the length of forearm bones greater is the carrying angle. So the carrying angle is more in shorter persons as compared to taller persons. It is abduction at the shoulder and not the carrying angle which keeps the swinging upper limbs away from the side of the pelvis during walking. Carrying angle is not a secondary sex character. The type of fracture a child sustains after fall on outstretched hand is also determined by the value of the carrying angle. A new type of fracture hitherto undescribed in the literature, T-Y fracture of the distal humeral epiphysis is also reported. 相似文献
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The present investigation was carried out to study the effect of tumor growth on the spleen of an aged host. Dalton's lymphoma (DL), a spontaneous T cell lymphoma, was grown in mice of different age groups classified as young, adult or old on the basis of their reproductive status. Splenocytes obtained from normal and tumor-bearing young, adult and old mice were checked for an in vitro blastogenic response to concanavalin A (Con A), colony-forming ability and apoptosis. There was an enhanced apoptosis of splenocytes and a concomitant inhibition of splenocyte blastogenesis and their responsiveness to the mitogenic stimulus of Con A in aged mice. The counts of granulocyte macrophage- and macrophage-colony forming units were significantly enhanced in the spleen of tumor-bearing adult mice. It is proposed that the DL-growth-dependent increase in the size of the spleen in adult mice is due to an increased blastogenesis of splenocytes, which, however, may not be applicable in the case of old tumor-bearing mice. The role of splenic macrophages in the regulation of the functions of the spleen by macrophage-derived NO is shown. 相似文献
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Fernandes Priyanka Wang Karina Timmerman Jason Reyes Angela Holmes Faye Olaleye Omonike A. Salihu Hamisu M. Moerchen Victoria A. Belcher Harolyn M. E. Copeland-Linder Nikeea Noble Charlotte A. Vamos Cheryl A. Armstrong Anna Waters Catrina R. Long-White Deneen Brown Claudia Reddy Madhavi M. Kuo Alice 《Maternal and child health journal》2022,26(7):1415-1423
Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from... 相似文献
8.
Priyanka Sharma Guojun Wu Deeptha Kumaraswamy Natalie Burchat Hong Ye Yongjia Gong Liping Zhao Yan Y. Lam Harini Sampath 《Nutrients》2021,13(2)
7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies. 相似文献
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Chuyuan Wang Patricia Solís Lily Villa Nayan Khare Elizabeth A. Wentz Aaron Gettel 《Journal of urban health》2021,98(3):344
The objective of the present study was to examine the effects of a confluence of demographic, socioeconomic, housing, and environmental factors that systematically contribute to heat-related morbidity in Maricopa County, Arizona, from theoretical, empirical, and spatial perspectives. The present study utilized ordinary least squares (OLS) regression and multiscale geographically weighted regression (MGWR) to analyze health data, U.S. census data, and remotely sensed data. The results suggested that the MGWR model showed a significant improvement in goodness of fit over the OLS regression model, which implies that spatial heterogeneity is an essential factor that influences the relationship between these factors. Populations of people aged 65+, Hispanic people, disabled people, people who do not own vehicles, and housing occupancy rate have much stronger local effects than other variables. These findings can be used to inform and educate local residents, communities, stakeholders, city managers, and urban planners in their ongoing and extensive efforts to mitigate the negative impacts of extreme heat on human health in Maricopa County. 相似文献
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