Background The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. Methods We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. Results A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score–matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score–matched analysis. Conclusions Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.)

DNA and RNA can be assayed rapidly and very sensitively by exploiting the enhanced fluorescence of ethidium intercalated into duplex regions. By assaying at different pHs and introducing a heating/cooling cycle, a great many physicochemical aspects of DNA and RNA can be studied avoiding the use of radiolabels, and often giving information not otherwise readily obtainable. Studies are described on duplex DNA which involve measurement of extinction coefficients, cross-linking by chemicals, Cot curve analysis as well as estimation of drug-DNA binding constants. The assays can be adapted to investigate multi-stranded nucleic acid structures. The use of covalently closed circular DNA also allows rapid and extremely sensitive measurements of nicking caused by irradiation or drugs.

A h r ta T6G 2EB Received July 25, 1972 MURRAY, N. L., and MORGAN, A. R. Enzymatic and physical studies on the triplex dT,.dA,.rU,.Can. 9. Biochem. 51, 436-449 (1973).The triplex dTn.dAn.rUn was studied as a model system both enzymatically and physically with a view that a rational approach for attempting to isolate triplexes from in vivo situations might emerge. The triplex was characterized by mixing curves and by its equilibrium buoyant density. In 5 mM Na phosphate, pH '5.3, for KCI concentrations below 0.4 ,W the triplex dissociated into dT,-dA, 4-rU,, dissociation being complete at about 0.3 M KC1. If MgCl? replaced KC1 a strongly cooperative dissociation mcurred at 1 ml$4 MgCla. Whereas with alkaline titration of dT, . dAn .rLJ,, rUn was dissociated first followed by dT,.dA,, acidic titration resulted in the whole triplex dissociating together. Both transcription and replication of dT,.dA, were strongly inhibited by formation of a triplex. The DNA and RNA moieties in the triplex are somewhat protected against DWase I and pancreatic RNase degradation, when compared with duplex dT, . dA, or rU,. Spermine binds equally well to dTn -dAn and dTn -dA, . r u n which is consistent with spermine binding in the minor groove and WNA in the major groove of DNA. MURRAY, N. L., et MORGAN, A. R. Enzymatic and physical studies on the triplex dT,-dA,.rU,. Can. J. Biochem. 51, 436-449 (1873). UtiHisant le triplet dT,.dA, . r u n comme un systkme anodkle, nous avons fait une etude enzymatique et physique dans le but de ~~C O U V H~E . une approche rationelle qui nous permettrait d'isoler des triplets itz v i v a Nous avons caractkrisk ce triplet par des courbes cambin6es et par sa densit6 de pousde B l'kquilibre. Dans une solution de phosphate de Na 5 m,W h pH 7.3, B e triplet se dissocie en d%,.dA, f rU, B des concentrations de KC1 au-dessous de 0:4 M, B a dissociation &ant csmplkte aux environs de 6.3 At. Si le MgClZ remplace le KCl, il se produit une dissociation fortemerat cooperative pour une concentration de MgC12, 1 m,W. Lors de la tiaration alcaline de dT,-$A,-rU,, le rU,, est cYabord dissocik et le dT,.dA, se dissocie ensuite. La titration acide dissocie en mCme temps le triplet entier. La transcription et la rkplication du dTn -dA, sont fortement inhibees par B a formation d'un triplet. Quand on les compare avec le doublet dT,.dA, ou avec r u n , les fractions ABN et ARN dans Ie triplet sont parfois protegees contre la degradation par lVADNase et 15ARNase pancreatique. La spermine se lie aussi bien au dTn.dAn qu'au dTn. dA,. rU,. La liaison de la spermine se ferait donc dans la gorge ktroite de 15ADW et celle de I'ARN, dans le gorge large de I'ADN.[Traduit par B e journal] PntrodactianThe dominance of Watson-Crick base pairing in polynucleotides has tended to result in the relegation of other base-pairing arrangements to the status of "'academic interest only". Hoogsteen base pairing (1) is not only found in crystals of simple derivatives sf the bases but in polynucleotide three-stranded helices (triplexes). A r...

The western United States has experienced increasing wildfire activities, which have negative effects on human health. Epidemiological studies on fine particulate matter (PM2.5) from wildfires are limited by the lack of accurate high-resolution PM2.5 exposure data over fire days. Satellite-based aerosol optical depth (AOD) data can provide additional information in ground PM2.5 concentrations and has been widely used in previous studies. However, the low background concentration, complex terrain, and large wildfire sources add to the challenge of estimating PM2.5 concentrations in the western United States. In this study, we applied a Bayesian ensemble model that combined information from the 1 km resolution AOD products derived from the Multi-angle Implementation of Atmospheric Correction (MAIAC) algorithm, Community Multiscale Air Quality (CMAQ) model simulations, and ground measurements to predict daily PM2.5 concentrations over fire seasons (April to September) in Colorado for 2011–2014. Our model had a 10-fold cross-validated R2 of 0.66 and root-mean-squared error of 2.00 μg/m3, outperformed the multistage model, especially on the fire days. Elevated PM2.5 concentrations over large fire events were successfully captured. The modeling technique demonstrated in this study could support future short-term and long-term epidemiological studies of wildfire PM2.5.

Ambient fine particulate matter less than 2.5 μm in aerodynamic diameter (PM 2.5) has been linked to various adverse health outcomes. PM 2.5 arises from both natural and anthropogenic sources, and PM 2.5 concentrations can vary over space and time. However, the sparsity of existing air quality monitors greatly restricts the spatial-temporal coverage of PM 2.5 measurements, potentially limiting the accuracy of PM 2.5-related health studies. Various methods exist to address these limitations by supplementing air quality monitoring measurements with additional data. We develop a method to combine PM 2.5 estimated from satellite-retrieved aerosol optical depth (AOD) and chemical transport model (CTM) simulations using statistical models. While most previous methods utilize AOD or CTM separately, we aim to leverage advantages offered by both data sources in terms of resolution and coverage using Bayesian ensemble averaging. Our approach differs from previous ensemble approaches in its ability to not only incorporate uncertainties in PM 2.5 estimates from individual models but also to provide uncertainties for the resulting ensemble estimates. In an application of estimating daily PM 2.5 in the Southeastern US, the ensemble approach outperforms previously developed spatial-temporal statistical models that use either AOD or bias-corrected CTM simulations in cross-validation (CV) analyses. More specifically, in spatially clustered CV experiments, the ensemble approach reduced the AOD-only and CTM-only model's root mean squared error (RMSE) by at least 13%. Similar improvements were seen in R 2. The enhanced prediction performance that the ensemble technique provides at fine-scale spatial resolution, as well as the availability of prediction uncertainty, can be further used in health effect analyses of air pollution exposure.