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101.
Bernt Popp Svein I St?ve Sabine Endele Line M Myklebust Juliane Hoyer Heinrich Sticht Silvia Azzarello-Burri Anita Rauch Thomas Arnesen André Reis 《European journal of human genetics : EJHG》2015,23(5):602-609
Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity. 相似文献
102.
Jargalsaikhan Dagvadorj Karolina Mikulska-Ruminska Gantsetseg Tumurkhuu Rojo A. Ratsimandresy Jessica Carriere Allen M. Andres Stefanie Marek-Iannucci Yang Song Shuang Chen Malcolm Lane Andrea Dorfleutner Roberta A. Gottlieb Christian Stehlik Suzanne Cassel Fayyaz S. Sutterwala Ivet Bahar Timothy R. Crother Moshe Arditi 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(1)
103.
Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies
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![点击此处可从《Human mutation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Diane Van Opstal Femke de Vries Lutgarde Govaerts Marjan Boter Debora Lont Stefanie van Veen Marieke Joosten Karin Diderich Robert‐Jan Galjaard Malgorzata I. Srebniak 《Human mutation》2015,36(3):319-326
We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5‐Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age‐ or screening‐related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early‐onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early‐onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late‐onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication. 相似文献
104.
Initial graft size and not the innate immune response limit survival of engrafted neural stem cells
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Stefanie Vogel Markus Aswendt Melanie Nelles Nadine Henn Gabriele Schneider Mathias Hoehn 《Journal of tissue engineering and regenerative medicine》2018,12(3):784-793
Transplantation of neural stem cells (NSCs) appears to be a promising regenerative therapy for a variety of neurological disorders. Nevertheless, NSC engraftment is limited by the number of surviving cells. To maximize stem cell‐mediated effects, timing of implantation and cell number have to be precisely evaluated. Here, a transgenic murine NSC line was optimized for high expression levels of the imaging reporters Luc2 and copGFP. NSCs of 150 000, 75 000, 15 000 or 1500 cells or Hanks buffered salt solution were implanted into the striatum of nude mice. The survival of NSCs was monitored with in vivo bioluminescence imaging (BLI) over 2 weeks and brain sections were histologically analysed for glial cells of the innate immune system. The longitudinal in vivo BLI data revealed a significantly reduced viability with the highest rate for 150 000 engrafted NSCs. The cell loss was not correlated with the number of Iba‐1+ immune cells nor GFAP+ astrocytes. Histological quantification of copGFP+ cells at 14 days postimplantation confirmed the in vivo data with the highest density of copGFP+ cells in the 150 000‐cell graft and the highest survival rate for 1500 cells/graft. In conclusion, regenerative therapies should strictly evaluate the maximal number of stem cells to be transplanted in one location, as the results suggest that there is a critical limit of cells able to survive in the adult brain. Survival is limited by availability of oxygen and nutrients but not the inflammatory response induced by the implantation. 相似文献
105.
Stefanie Ebelt Sarnat Andrea Winquist James J. Schauer Jay R. Turner Jeremy A. Sarnat 《Environmental health perspectives》2015,123(5):437-444
Background:
Given that fine particulate matter (≤ 2.5 μm; PM2.5) is a mixture of multiple components, it has been of high interest to identify its specific health-relevant physical and/or chemical features.Objectives:
We conducted a time-series study of PM2.5 and cardiorespiratory emergency department (ED) visits in the St. Louis, Missouri–Illinois metropolitan area, using 2 years of daily PM2.5 and PM2.5 component measurements (including ions, carbon, particle-phase organic compounds, and elements) made at the St. Louis-Midwest Supersite, a monitoring site of the U.S. Environmental Protection Agency Supersites ambient air monitoring research program.Methods:
Using Poisson generalized linear models, we assessed short-term associations between daily cardiorespiratory ED visit counts and daily levels of 24 selected pollutants. Associations were estimated for interquartile range changes in each pollutant. To allow comparison of relationships among multiple pollutants and outcomes with potentially different lag structures, we used 3-day unconstrained distributed lag models controlling for time trends and meteorology.Results:
Considering results of our primary models, as well as sensitivity analyses and models assessing co-pollutant confounding, we observed robust associations of cardiovascular disease visits with 17α(H),21β(H)-hopane and congestive heart failure visits with elemental carbon. We also observed a robust association of respiratory disease visits with ozone. For asthma/wheeze, associations were strongest with ozone and nitrogen dioxide; observed associations of asthma/wheeze with PM2.5 and its components were attenuated in two-pollutant models with these gases. Differential measurement error due to differential patterns of spatiotemporal variability may have influenced patterns of observed associations across pollutants.Conclusions:
Our findings add to the growing field examining the health effects of PM2.5 components. Combustion-related components of the pollutant mix showed particularly strong associations with cardiorespiratory ED visit outcomes.Citation:
Sarnat SE, Winquist A, Schauer JJ, Turner JR, Sarnat JA. 2015. Fine particulate matter components and emergency department visits for cardiovascular and respiratory diseases in the St. Louis, Missouri–Illinois, metropolitan area. Environ Health Perspect 123:437–444; http://dx.doi.org/10.1289/ehp.1307776 相似文献106.
107.
Combined Influence of Gestational Weight Gain and Estimated Fetal Weight on Risk Assessment for Small‐ or Large‐for‐Gestational‐Age Birth Weight: A Prospective Cohort Study
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![点击此处可从《Journal of ultrasound in medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
108.
Tjallie van der Kooi Hugo Sax Didier Pittet Jaap van Dissel Birgit van Benthem Bernhard Walder Vanessa Cartier Lauren Clack Sabine de Greeff Martin Wolkewitz Stefanie Hieke Hendriek Boshuizen Jan van de Kassteele Annemie Van den Abeele Teck Wee Boo Magda Diab-Elschahawi Uga Dumpis Camelia Ghita Susan FitzGerald Tatjana Lejko Kris Leleu Mercedes Palomar Martinez Olga Paniara Márta Patyi Paweł Schab Annibale Raglio Emese Szilágyi Mirosław Ziętkiewicz Albert W. Wu Hajo Grundmann Walter Zingg On behalf of the PROHIBIT consortium 《Intensive care medicine》2018,44(1):48-60
Purpose
To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators.Methods
Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance.Results
Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions.Conclusions
This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.109.
Stefanie?N.?RezansoffEmail author Akm?Moniruzzaman Elenore?Clark Julian?M.?Somers 《Substance abuse treatment, prevention, and policy》2015,10(1):42
Background
The majority of Drug Treatment Court (DTC) research has examined the impact of DTCs on criminal recidivism. Comparatively little research has addressed the association between DTC participation and engagement with community-based health and social services. The present study investigated changes in participant involvement with outpatient healthcare and income assistance within a DTC cohort. We hypothesized that involvement with community-based (outpatient) health and social services would increase post-DTC participation, and that service levels would be higher among program graduates and offenders with histories of co-occurring mental and substance use disorders.Methods
Participants were 631 offenders at the DTC in Vancouver, Canada (DTCV). Administrative data representing hospital, outpatient medical care, and income assistance were examined one-year pre/post program to assess differences over time. Generalized estimating equations were used to investigate the association between changes in service use and program involvement. We also examined the relationship between level of service use and offender characteristics.Results
Members of the cohort were disproportionately Aboriginal (33 %), had been sentenced 2.7 times in the 2 years preceding their index offence, and 50 % had been diagnosed with a non substance-related mental disorder in the five years preceding the index offence. The mean number of outpatient services post DTCV was 51, and the mean amount of social assistance paid was $5,897. Outpatient service use increased following exposure to DTCV (Adjusted Rate Ratio (ARR)?=?1.45) and was significantly higher among women (ARR?=?1.47), program graduation (ARR?=?1.23), and those previously diagnosed with concurrent substance use and mental disorders (ARR?=?4.92). Overall, hospital admissions did not increase post-program, although rates were significantly higher among women (ARR?=?1.76) and those with concurrent disorders (ARR?=?2.71). Income assistance increased significantly post program (ARR?=?1.16), and was significantly higher among women (ARR?=?1.03), and those diagnosed with substance use disorders (ARR?=?1.42) and concurrent disorders (ARR?=?1.72).Conclusions
These findings suggest that the DTCV was a catalyst for increased participant engagement with community health and social supports, and that rates of service use were consistently higher among women and individuals with concurrent disorders. Research is needed to investigate the potential link between health and social support and reductions in recidivism associated with DTCs.110.
Michael J Curtis Richard A Bond Domenico Spina Amrita Ahluwalia Stephen P A Alexander Mark A Giembycz Annette Gilchrist Daniel Hoyer Paul A Insel Angelo A Izzo Andrew J Lawrence David J MacEwan Lawrence D F Moon Sue Wonnacott Arthur H Weston John C McGrath 《British journal of pharmacology》2015,172(14):3461-3471