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Heterozygous Mutations in Natriuretic Peptide Receptor‐B (NPR2) Gene as a Cause of Short Stature 下载免费PDF全文
Sophie R. Wang Christina M. Jacobsen Heather Carmichael Aaron B. Edmund Jerid W. Robinson Robert C. Olney Timothy C. Miller Jennifer E. Moon Veronica Mericq Lincoln R. Potter Matthew L. Warman Joel N. Hirschhorn Andrew Dauber 《Human mutation》2015,36(4):474-481
Based on the observation of reduced stature in relatives of patients with acromesomelic dysplasia, Maroteaux type (AMDM), caused by homozygous or compound heterozygous mutations in natriuretic peptide receptor‐B gene (NPR2), it has been suggested that heterozygous mutations in this gene could be responsible for the growth impairment observed in some cases of idiopathic short stature (ISS). We enrolled 192 unrelated patients with short stature and 192 controls of normal height and identified seven heterozygous NPR2 missense or splice site mutations all in the short stature patients, including one de novo splice site variant. Three of the six inherited variants segregated with short stature in the family. Nine additional rare nonsynonymous NPR2 variants were found in three additional cohorts. Functional studies identified eight loss‐of‐function mutations in short individuals and one gain‐of‐function mutation in tall individuals. With these data, we were able to rigorously verify that NPR2 functional haploinsufficiency contributes to short stature. We estimate a prevalence of NPR2 haploinsufficiency of between 0 and 1/26 in people with ISS. We suggest that NPR2 gain of function may be a more common cause of tall stature than previously recognized. 相似文献
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Pangal Dhiraj J. Wishart Danielle Shiroishi Mark S. Ruzevick Jacob Carmichael John D. Zada Gabriel 《Pituitary》2022,25(3):480-485
Pituitary - Patterns of extension of pituitary adenomas (PA) may vary according to PA subtype. Understanding extrasellar extension patterns in growth hormone PAs (GHPA) vis-a-vis nonfunctional PAs... 相似文献
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Felicia R. Simpson Owen Carmichael Kathleen M. Hayden Christina E. Hugenschmidt Jeanne M. McCaffery Sevil Yasar Nicholas M. Pajewski Mark A. Espeland 《Journal of diabetes and its complications》2021,35(5):107909
AimsTo assess whether there is an opportune window when intensive lifestyle intervention (ILI) benefits cognitive function.MethodsStandardized cognitive assessments were collected following ≥8 years of either ILI or a control condition of diabetes support and education (DSE) in 3708 individuals, ages 45-76 years at enrollment, with type 2 diabetes and overweight or obesity. Frailty index (FI) scores were used to group individuals at baseline into tertiles according to their age-related health status. Linear models were used to describe intervention adherence and cognitive function, with interaction terms to examine the consistency of relationships among tertiles.ResultsWorse baseline FI scores were associated with poorer subsequent performance in tests of attention, processing speed, and executive function. No differences in any measure of cognitive function were observed between intervention groups within any FI tertile (all p > 0.10). Among individuals with worse baseline FI scores, weight gain was associated with poorer global cognitive function among participants assigned to DSE. There was no association between weight changes and cognitive function among participants assigned to ILI.ConclusionsAmong adults with type 2 diabetes and overweight/obesity, we found no evidence that there is a window of opportunity based on FI when ILI benefits cognitive function. 相似文献
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Mark A. Espeland PhD Jose A. Luchsinger MD MPH Rebecca H. Neiberg MS Owen Carmichael PhD Paul J. Laurienti PhD Xavier Pi‐Sunyer MD Rena R. Wing PhD Delilah Cook CCRP Edward Horton MD Ramon Casanova PhD Kirk Erickson PhD R. Nick Bryan MD the Action for Health in Diabetes Brain Magnetic Resonance Imaging Research Group 《Journal of the American Geriatrics Society》2018,66(1):120-126
Objectives
To determine whether long‐term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF ) in individuals with type 2 diabetes mellitus.Design
Postrandomization assessment of CBF.Setting
Action for Health in Diabetes multicenter randomized controlled clinical trial.Participants
Individuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310).Interventions
A multidomain intensive lifestyle intervention (ILI ) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE ), a control condition.Measurements
Participants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI ) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization.Results
Weight changes from baseline to time of MRI averaged ?6.2% for ILI and ?2.8% for DSE (P < .001), and increases in self‐reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL /100 g per minute, 95% confidence interval (CI ) = 0.07–6.70 mL /100 g per minute) and occipital lobes (3.52 mL /100 g per minute, 95% CI = 0.20–6.84 mL /100 g per minute). In ILI , greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02).Conclusions
Long‐term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF .39.
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PE Saide GR Carmichael SN Spak P Minnis JK Ayers 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(30):11939-11943
Limitations in current capabilities to constrain aerosols adversely impact atmospheric simulations. Typically, aerosol burdens within models are constrained employing satellite aerosol optical properties, which are not available under cloudy conditions. Here we set the first steps to overcome the long-standing limitation that aerosols cannot be constrained using satellite remote sensing under cloudy conditions. We introduce a unique data assimilation method that uses cloud droplet number (N(d)) retrievals to improve predicted below-cloud aerosol mass and number concentrations. The assimilation, which uses an adjoint aerosol activation parameterization, improves agreement with independent N(d) observations and with in situ aerosol measurements below shallow cumulus clouds. The impacts of a single assimilation on aerosol and cloud forecasts extend beyond 24 h. Unlike previous methods, this technique can directly improve predictions of near-surface fine mode aerosols responsible for human health impacts and low-cloud radiative forcing. Better constrained aerosol distributions will help improve health effects studies, atmospheric emissions estimates, and air-quality, weather, and climate predictions. 相似文献