Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in etiology of ACDMPV.

The stress imposed by the COVID-19 pandemic and ensuing social isolation could adversely affect sleep. As sleep problems may persist and hurt health, it is important to identify which populations have experienced changes in sleeping patterns during the pandemic and their extent. Methods: In Study 1, 3,062 responders from 49 countries accessed the survey website voluntarily between March 26 and April 26, 2020, and 2,562 (84%; age: 45.2 ± 14.5, 68% women) completed the study. In Study 2, 1,022 adult US responders were recruited for pay through Mechanical Turk, and 971 (95%; age 40.4 ± 13.6, 52% women) completed the study. The survey tool included demographics and items adapted from validated sleep questionnaires on sleep duration, quality and timing, and sleeping pills consumption. Results: In Study 1, 58% of the responders were unsatisfied with their sleep. Forty percent of the responders reported a decreased sleep quality vs before COVID-19 crisis. Self-reported sleeping pill consumption increased by 20% (P < .001). Multivariable analysis indicated that female sex, being in quarantine, and 31-to 45-years age group, reduced physical activity and adverse impact on livelihood were independently associated with more severe worsening of sleep quality during the pandemic. The majority of findings were reproduced in the independent cohort of Study 2. Conclusions: Changes imposed due to the pandemic have led to a surge in individuals reporting sleep problems across the globe. The findings raise the need to screen for worsening sleep patterns and use of sleeping aids, especially in more susceptible populations, namely, women and people with insecure livelihoods subjected to social isolation.

Plasmids p749, p106, and p150 contain cDNA inserts complementary to rat skeletal muscle actin mRNA. Nucleotide sequence analysis indicates the following sequence relationships: p749 specifies codons 171 to 360; p150 specifies codons 357 to 374 together with 120 nucleotides of the 3'-non-translated region; p106 specifies the last actin amino acid codon, the termination codon and the entire 3' non-translated region. Plasmid p749 hybridized with RNA extracted from rat skeletal muscle, cardiac muscle, smooth (stomach) muscle, and from brain. It also hybridizes well with RNA extracted from skeletal muscle and brain of dog and chick. Plasmid p106 hybridized specifically with rat striated muscles (skeletal and cardiac muscle) mRNA but not with mRNA from rat stomach and from rat brain. It also hybridized to RNA extracted from skeletal muscle of rabbit and dog but not from chick. Thermal stability of the hybrids and sensitivity to S1 digestion also indicated substantial divergence between the 3' untranslated end of rat and dog skeletal muscle actins. The investigation shows that the coding regions of actin genes are highly conserved, whereas the 3' non-coding regions diverged considerably during evolution. Probes constructed from the 3' non-coding regions of actin mRNAs can be used to identify the various actin mRNA and actin genes.

Macrolide administration for asthma for three or more weeks was not associated with improvement in FEV1, but produced significant improvements in peak expiratory flow, symptoms, quality of life, and airway hyper-reactivity. Macrolides may therefore be beneficial as adjunct asthma therapy. Future trials, focusing on long-term safety and effectiveness, should use standardized outcomes and procedures.