Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.
Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2 -resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes -is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (V max /K m ) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.
Despite worldwide dissemination of New Delhi metallo-β-lactamase1 (blaNDM-1), outbreaks remain uncommon in China. In this study, we describe the characteristics of the outbreak-related blaNDM-1-producing K. pneumonia isolates in a neonatal unit in Shandong province, China. We recovered 21 non-repetitive carbapenem-resistant K. pneumoniae isolates with a positively modified Hodge test (MHT) or EDTA synergistic test from patients and environmental samples in Shandong provincial hospital. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) data show K. pneumoniae isolates from 19 patients were clonally related and belong to the clonal groups ST20 and ST17. We note two outbreaks, the first caused by ST20 during August 2012 involving four patients, and the second caused by ST20 and ST17 during January 2012 and September 2013 involving fourteen patients. We found the bed railing of one patient was the source of the outbreak. We verified the presence of the blaNDM-1 gene in 21 K. pneumoniae isolates. The genes blaCTX-M-15, blaCTX-M-14, blaDHA-1, blaTEM-1 and Class I integron were also present in 18 (85.7%), 3 (14.3%), 18 (85.7%), 19 (90.5%) and 19 (90.5%) isolates, respectively. We also found an isolate with both blaNDM-1 and blaIMP-4. All of the isolates exhibited a multidrug-resistance phenotype. The β-lactam resistance of 20 isolates was transferable via conjugation. In addition, we show the resistance of 21 K. pneumoniae isolates to carbapenem is not related to lack of outer-membrane proteins OmpK35 and OmpK36 nor overpression of efflux pumps. This study provides the first report confirming blaNDM-1-producing K. pneumoniae ST20 and ST17 were associated with outbreak. Early detection of resistance genes is an effective strategy in preventing and controlling infection by limiting the dissemination of these organisms.
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