Severe Myocardial Fibrosis Caused by a Deletion of the 5’ End of the Lamin A/C Gene J. Peter van Tintelen, Rene A. Tio, Wilhelmina S. Kerstjens-Frederikse, Jop H. van Berlo, Ludolf G. Boven, Albert ...J. H. Suurmeijer, Stefan J. White, Johan T. den Dunnen, Gerard J. te Meerman, Yvonne J. Vos, Annemarie H. van der Hout, Jan Osinga, Maarten P. van den Berg, Dirk J. van Veldhuisen, Charles H. C. M. Buys, Robert M. W. Hofstra, Yigal M. Pinto In a large family with an autosomal, dominantly inherited form of myocardial fibrosis with a highly malignant clinical outcome, we identified a deletion containing the start codon of the lamin AC gene, which had been missed by the regular mutation-detection systems. Myocardial fibrosis was already detected in early stages of the disease even without overt signs of heart failure. In vitro studies demonstrated that the deletion resulted in the formation of nuclear aggregates of lamin, suggesting that the mutant allele was being transcribed.
Abstract Objective To determine if there is an association between longer breast-feeding duration and dental caries in healthy urban children. Methods We conducted a cross-sectional study of urban ...children aged 1 to 6 years recruited through The Applied Research Group for Kids (TARGet Kids!) practice-based research network between September 2011 and August 2013. The main outcome measure was parental report of dental caries. Results The adjusted predicted probability of dental caries was 7%, 8%, 11%, and 16% with total duration of breast-feeding duration of 12, 18, 24, and 36 months, respectively. In the adjusted logistic regression analyses, relative to breast-feeding 0 to 5 months, the odds of dental caries with total breast-feeding duration >24 months was 2.75 (95% confidence interval 1.61–4.72). Conclusions Among healthy urban children, longer breast-feeding duration was associated with higher odds of dental caries. These findings support heightened awareness and enhanced anticipatory guidance for preventive dental care, particularly among children who breast-feed beyond 2 years of age.
Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such ...cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status.
Influenza virus is a major cause of acute hypoxemic respiratory failure. Early identification of patients who will suffer severe complications can help stratify patients for clinical trials and plan ...for resource use in case of pandemic.
We aimed to identify which clinical variables best predict prolonged acute hypoxemic respiratory failure in influenza-infected critically ill children. Acute hypoxemic respiratory failure was defined using hypoxemia cutoffs from international consensus definitions of acute respiratory distress syndrome in patients with ventilatory support. Prolonged acute hypoxemic respiratory failure was defined by acute hypoxemic respiratory failure criteria still present at PICU day 7.
In this prospective multicenter study across 34 PICUs from November 2009 to April 2018, we included children (< 18 yr) without comorbid risk factors for severe disease.
We used a Monte Carlo cross validation method with
random train-test splits at a 70-30% proportion per model.
Using clinical data at admission (day 1) and closest to 8 am on PICU day 2, we calculated the area under the receiver operating characteristic curve using random forests machine learning algorithms and logistic regression.
We included 258 children (median age = 6.5 yr) and 11 (4.2%) died. By day 2, 65% (
= 165) had acute hypoxemic respiratory failure dropping to 26% (
= 67) with prolonged acute hypoxemic respiratory failure by day 7. Those with prolonged acute hypoxemic respiratory failure had a longer ICU stay (16.5 vs 4.0 d;
< 0.001) and higher mortality (13.4% vs 1.0%). A multivariable model using random forests with 10 admission and eight day 2 variables performed best (0.93 area under the receiver operating characteristic curve; 95 CI%: 0.90-0.95) where respiratory rate, Fio
, and pH on day 2 were the most important factors.
In this prospective multicentric study, most children with influenza virus-related respiratory failure with prolonged acute hypoxemic respiratory failure can be identified early in their hospital course applying machine learning onto routine clinical data. Further validation is needed prior to bedside implementation.
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