Assessing Positive Child Health among Individuals Born Extremely Preterm

OBJECTIVE: To assess the development of a Positive Child Health Index (PCHI) based on 11 adverse outcomes and evaluate the association of PCHI with quality of life (QoL) scores in a preterm cohort. STUDY DESIGN: A total of 889 children enrolled in the Extremely Low Gestational Age Newborn (ELGAN) study in 2002-2004 were followed up at 10 years of age. A parent/caregiver completed questionnaires for child QoL, asthma, visual or hearing impairment, gross motor function impairment, epilepsy, attention deficit/hyperactivity disorder, anxiety, and depression. The child was assessed for cognitive impairment, autism, and obesity. PCHI scores were computed and linear regression models were used to evaluate the relationship between QoL categories (psychosocial, physical, emotional, social, school, and total) and the PCHI (dichotomized and coded as a multilevel categorical predictor) and to assess sex differences. RESULTS: Among ELGAN children, higher PCHI scores were associated with higher reported QoL scores for all QoL categories. Children with no disorders and a PCHI of 100% had Pediatric Quality of Life Inventory total scores that were 11 points higher than children with 1 or more adverse outcomes (PCHI of <100%). Boys had lower QoL scores for the total, psychosocial, social, and school categories. CONCLUSIONS: Positive child health assessed using a quantitative PCHI was associated with QoL across the ELGAN cohort at school age. In the current study, the PCHI encompassed 11 outcomes assessed in ELGANs. Future research could include an enhanced panel of child health outcomes to support the use of PCHI as an indicator of positive child health

Effects of Changing Work Environments on Employer Support for Physical Activity During COVID-19

COVID-19 dramatically accelerated evolving changes in the way we define the “work environment” in the United States. In response to COVID-19, many employers have offered increased flexibility for where employees work, including remote (an employee’s workstation is at home) and hybrid work (an employee works both at the employer worksite and remotely, on predetermined schedules). Accordingly, worksite physical activity (PA) and sedentary behaviors (SB) such as extended sitting time (ST) may have changed.1,2 However, little is known about whether these work arrangements are associated with changes in employer support for PA. Interviews were conducted to assess this gap in understanding. Because little is known about employer support for equity with respect to PA and SB, this study sought to identify potential strategies to assure equity in PA opportunities across work environments

Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings

Rapid-onset dystonia-parkinsonism (RDP) is a movement disorder associated with mutations in the ATP1A3 gene. Signs and symptoms of RDP commonly occur in adolescence or early adulthood and can be triggered by physical or psychological stress. Mutations in ATP1A3 are also associated with alternating hemiplegia of childhood (AHC). The neuropathologic substrate of these conditions is unknown. The central nervous system of four siblings, three affected by RDP and one asymptomatic, all carrying the I758S mutation in the ATP1A3 gene, was analyzed. This neuropathologic study is the first carried out in ATP1A3 mutation carriers, whether affected by RDP or AHC. Symptoms began in the third decade of life for two subjects and in the fifth for another. The present investigation aimed at identifying, in mutation carriers, anatomical areas potentially affected and contributing to RDP pathogenesis. Comorbid conditions, including cerebrovascular disease and Alzheimer disease, were evident in all subjects. We evaluated areas that may be relevant to RDP separately from those affected by the comorbid conditions. Anatomical areas identified as potential targets of I758S mutation were globus pallidus, subthalamic nucleus, red nucleus, inferior olivary nucleus, cerebellar Purkinje and granule cell layers, and dentate nucleus. Involvement of subcortical white matter tracts was also evident. Furthermore, in the spinal cord, a loss of dorsal column fibers was noted. This study has identified RDP-associated pathology in neuronal populations, which are part of complex motor and sensory loops. Their involvement would cause an interruption of cerebral and cerebellar connections which are essential for maintenance of motor control. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1279-x) contains supplementary material, which is available to authorized users

Short-term variability in euphotic zone biogeochemistry and primary productivity at Station ALOHA : a case study of summer 2012

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 29 (2015): 1145–1164, doi:10.1002/2015GB005141.Time-series observations are critical to understand the structure, function, and dynamics of marine ecosystems. The Hawaii Ocean Time-series program has maintained near-monthly sampling at Station ALOHA (22°45′N, 158°00′W) in the oligotrophic North Pacific Subtropical Gyre (NPSG) since 1988 and has identified ecosystem variability over seasonal to interannual timescales. To further extend the temporal resolution of these near-monthly time-series observations, an extensive field campaign was conducted during July–September 2012 at Station ALOHA with near-daily sampling of upper water-column biogeochemistry, phytoplankton abundance, and activity. The resulting data set provided biogeochemical measurements at high temporal resolution and documents two important events at Station ALOHA: (1) a prolonged period of low productivity when net community production in the mixed layer shifted to a net heterotrophic state and (2) detection of a distinct sea-surface salinity minimum feature which was prominent in the upper water column (0–50 m) for a period of approximately 30 days. The shipboard observations during July–September 2012 were supplemented with in situ measurements provided by Seagliders, profiling floats, and remote satellite observations that together revealed the extent of the low productivity and the sea-surface salinity minimum feature in the NPSG.NOAA Climate Observation Division; National Science Foundation (NSF) Center for Microbial Oceanography: Research and Education (C-MORE) Grant Numbers: EF0424599, OCE-1153656, OCE-1260164; Gordon and Betty Moore Foundation Marine Microbiology Investigator2016-02-1

Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment

Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.Damon Runyon Cancer Research Foundation (DRG 2032-09)Damon Runyon Cancer Research Foundation (DFS 04-12)European Molecular Biology Organization (Long-term Fellowship)National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098179)National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098188)Smith Family FoundationPew Charitable Trusts. Program in the Biomedical Science

Research conference summary from the 2014 International Task Force on

OBJECTIVE: METHODS: In 2014, the Alternating Hemiplegia of Childhood Foundation hosted a multidisciplinary workshop intended to address fundamental challenges surrounding the diagnosis and management of individuals with RESULTS: Workshop attendees were charged with the following: (1) to achieve consensus on expanded diagnostic criteria to facilitate the identification of additional patients, intended to supplement existing syndrome-specific diagnostic paradigms; (2) to standardize definitions for the broad range of paroxysmal manifestations associated with AHC to disseminate to families; (3) to create clinical recommendations for common recurrent issues facing families and medical care providers; (4) to review data related to the death of individuals in the Alternating Hemiplegia of Childhood Foundation database to guide future efforts in identifying at-risk subjects and potential preventative measures; and (5) to identify critical gaps where we most need to focus national and international research efforts. CONCLUSIONS: This report summarizes recommendations of the workshop committee, highlighting the key phenotypic features to facilitate the diagnosis of possibl

Modifier Effects between Regulatory and Protein-Coding Variation

Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants