47 research outputs found

    Disability among young adults with congenital heart defects: Congenital heart survey to recognize outcomes, needs, and well-being 2016–2019

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    BACKGROUND: Disabilities have implications for health, well-being, and health care, yet limited information is available on the percentage of adults with congenital heart defects (CHD) living with disabilities. We evaluated the prevalence of disability and associated characteristics among the 2016–2019 CH STRONG (Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being) population-based sample of 19-to 38-year-olds with CHD from 3 US locations. METHODS AND RESULTS: Prevalence of disability types (hearing, vision, cognition, mobility, self-care, living independently) were compared with similarly aged adults from the general population as estimated by the American Community Survey and standardized to the CH STRONG eligible population to reduce nonresponse bias and confounding. Health-related quality of life (HRQOL) was measured via Patient-Reported Outcomes Measurement Information System Global Health Scale T-scores standardized to US 18-to 34-year-olds. Separate multivariable regression models assessed associations between disability and HRQOL. Of 1478 participants, 40% reported disabilities, with cognition most prevalent (29%). Of those reporting disability, 45% ever received disability benefits and 46% were unemployed. Prevalence of disability types were 5 to 8 times higher in adults with CHD than the general population. Those with ≥1 disability had greater odds of being female, and of having non-Hispanic Black maternal race and ethnicity, severe CHD, recent cardiac care, and noncardiac congenital anomalies. On average, adults with CHD and cognition, mobility, and self-care disabilities had impaired mental HRQOL and those with any disability type had impaired physical HRQOL. CONCLUSIONS: Two of 5 adults with CHD may have disabilities, which are associated with impaired HRQOL. These results may inform healthcare needs and services for this growing population. © 2021, American Heart Association Inc.. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    ALS-associated TBK1 variant p.G175S is defective in phosphorylation of p62 and impacts TBK1-mediated signalling and TDP-43 autophagic degradation

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    Mutations affecting SQSTM1 coding for p62 and TANK-Binding Kinase 1 (TBK1) have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TBK1 is a serine-threonine kinase that regulates p62's activity as an autophagy receptor via phosphorylation and also has roles in neuroinflammatory signalling pathways. The mechanisms underlying ALS and FTLD pathogenesis as a result of TBK1 mutations are incompletely understood, however, loss of TBK1 function can lead to dysregulated autophagy and mitophagy. Here, we report that an ALS-associated TBK1 variant affecting the kinase domain, p.G175S, is defective in phosphorylation of p62 at Ser-403, a modification critical for regulating its ubiquitin-binding function, as well as downstream phosphorylation at Ser-349. Consistent with these findings, expression of p.G175S TBK1 was associated with decreased induction of autophagy compared to wild type and reduced degradation of the ALS-linked protein TDP-43. Expression of wild type TBK1 increased NF-κB signalling ~300 fold in comparison to empty vector cells, whereas p.G175S TBK1 was unable to promote NF-κB signalling above levels observed in empty vector transfected cells. We also noted a hitherto unknown role for TBK1 as a suppressor of oxidative stress (Nrf2) signalling and show that p.G175S TBK1 expressing cells lose this inhibitory function. Our data suggest that TBK1 ALS mutations may broadly impair p62-mediated cell signalling, which ultimately may reduce neuronal survival, in addition TDP-43 was not efficiently degraded, together these effects may contribute to TBK1 mutation associated ALS and FTLD pathogenesis

    Fatigue Life Prediction for Panels Subjected to Thermo-Acoustic Loading

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    Measuring ecosystem function: consequences arising from variation in biomass-productivity relationships

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    Species diversity loss is expected to alter ecosystem function, but previous work has demonstrated inconsistent relationships between these two factors. Productivity is the most common measure of ecosystem function, but given the difficulty in measuring productivity, standing biomass or change in biomass are frequently used as proxy measures. A review of the recent ecosystem-function literature revealed that 93% of studies measure productivity as biomass, thereby assuming a strong positive relationship between these two variables. We tested this assumption by measuring biomass and productivity in seagrass beds in the Gulf of Mexico. We found that the relationship between standing biomass and productivity could be positive or negative, depending on site. Change in biomass over months inconsistently underestimated short-term productivity. The relationship between biomass and productivity may depend on plant age, successional stage, or site-specific rates of tissue loss to herbivory, senescence, or disturbance. Our results suggest that if biomass continues to be used as a measure of productivity without justification, highly productive communities that typically show little change in biomass, such as healthy climax communities, will not be interpreted as such. The conflicting results of previous studies investigating the relationship between diversity and productivity may be due to differences in the inherently variable relationship between biomass and productivity at different sites and scales.C.P. terHorst, and P. Mungui
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