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70 Childhood SES and Midlife CVD on Late-life Cognition
- Tamare V. Adrien, Andrew Hirst, Ai-Lin Tsai, Ruijia Chen, Eleanor Hayes-Larson, Shellie-Anne Levy, Laura Zahodne, Paul K. Crane, Rachel Peterson, Paola Gilsanz, Indira Turney
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 375
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Objective:
Cardiovascular disease (CVD) is a well-known risk factor for cognitive impairment and dementia, particularly among minoritized groups that have experienced a history of low childhood socioeconomic status (SES). Although previous literature has linked all levels of SES to varying degrees of stress exposure, children raised in higher SES households have more access to resources and services that encourage optimal growth and development than children who grow up in lower SES households. Given the disproportionate burden of dementia and cognitive deficits within minoritized groups, the present study examined whether childhood SES is associated with later life cognition among Black and White older adults and if this association persists after accounting for hypertension, a possible mediator of the relationship between childhood SES.
Participants and Methods:1,184 participants were from the first wave of the STAR (n = 397 Black [Mage= 75.0 ±6.8 years]) and KHANDLE (386 Black [Mage= 76.2 ±7.2 years] and 401 White [Mage= 78.4 ±7.5 years]) cohorts. We used general linear models to examine the relationship between childhood SES and later-life executive function, semantic memory, and verbal memory scores, and midlife hypertension. Childhood SES was measured by self-reported perceived financial status (with participants given the following options: ‘pretty well off financially’, ‘about average’, ‘poor’, or ‘it varied’). These models were assessed in the full sample and also stratified by race.
Results:In the full sample, childhood financial status was not associated with semantic memory, verbal episodic memory, or executive function. Financial status was associated with semantic memory in Black adults (β = -.124, t(771) = -2.52, p = .01) and this association persisted after accounting for hypertension (β = -.124, t(770) = -2.53, p = .01). There was no association between childhood financial status and later life semantic memory among White adults. There was no association between childhood financial status and later life verbal episodic memory or executive function in either Black or White adults in models with or without adjustment for hypertension.
Conclusions:Our findings showed no relationship between childhood SES and cognition, except for semantic memory in Black participants; this relationship persisted after accounting for midlife CVD. Future analyses will assess both direct and indirect effects of more predictive measures of childhood SES on late-life cognition with midlife CVD as a mediator.
Ten new insights in climate science 2021: a horizon scan
- Maria A. Martin, Olga Alcaraz Sendra, Ana Bastos, Nico Bauer, Christoph Bertram, Thorsten Blenckner, Kathryn Bowen, Paulo M. Brando, Tanya Brodie Rudolph, Milena Büchs, Mercedes Bustamante, Deliang Chen, Helen Cleugh, Purnamita Dasgupta, Fatima Denton, Jonathan F. Donges, Felix Kwabena Donkor, Hongbo Duan, Carlos M. Duarte, Kristie L. Ebi, Clea M. Edwards, Anja Engel, Eleanor Fisher, Sabine Fuss, Juliana Gaertner, Andrew Gettelman, Cécile A.J. Girardin, Nicholas R. Golledge, Jessica F. Green, Michael R. Grose, Masahiro Hashizume, Sophie Hebden, Helmke Hepach, Marina Hirota, Huang-Hsiung Hsu, Satoshi Kojima, Sharachchandra Lele, Sylvia Lorek, Heike K. Lotze, H. Damon Matthews, Darren McCauley, Desta Mebratu, Nadine Mengis, Rachael H. Nolan, Erik Pihl, Stefan Rahmstorf, Aaron Redman, Colleen E. Reid, Johan Rockström, Joeri Rogelj, Marielle Saunois, Lizzie Sayer, Peter Schlosser, Giles B. Sioen, Joachim H. Spangenberg, Detlef Stammer, Thomas N.S. Sterner, Nicola Stevens, Kirsten Thonicke, Hanqin Tian, Ricarda Winkelmann, James Woodcock
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- Journal:
- Global Sustainability / Volume 4 / 2021
- Published online by Cambridge University Press:
- 18 October 2021, e25
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Non-technical summary
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.
Technical summaryA synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.
Social media summaryHow do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
73565 Defining tp53 tumor suppressor functions in zebrafish embryonal rhabdomyosarcoma
- Kunal Baxi, Jiangfei Chen, Amanda Lipsitt, Nicole Hensch, Long Wang, Abhik Bandopadhyay, Aaron Sugalski, Andrea Gilbert, Eleanor Chen, Peter Houghton, Gail Tomlinson, Myron Ignatius
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, pp. 19-20
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ABSTRACT IMPACT: By assessing function of mutant (patient-specific) tp53 in zebrafish embryonal rhabdomyosarcoma will inform clinicians of the severity of mutant tp53 alleles. OBJECTIVES/GOALS: This study aims to define loss- and gain-of-function TP53 mutations by comparing effects in tp53-null and wild-type tumors. In addition, it aims to generate a rapid in vivo analysis platform to assign function to patient specific TP53 mutations in the clinic METHODS/STUDY POPULATION: To define tp53 function in ERMS pathogenesis, we previously generated a new tp53-null mutant (tp53-/-) in zebrafish by deleting the entire tp53 genomic locus using TALEN mutagenesis. tp53-/- zebrafish spontaneously develop a spectrum of tumors including sarcomas, leukemia and germ cell tumors (Ignatius…Baxi et. al., eLife) reminiscent of tumors observed in Trp53-null mice. Using the tp53-/- mutants to generate kRASG12D-induced ERMS, we discovered that tp53 is a potent repressor of metastases but rather surprisingly had no effect on self-renewal (Ignatius…Baxi et. al., eLife). Here, using tp53-/- zebrafish, we assessed effects of wild-type and mutant (patient specific) tp53 on tumor initiation, proliferation and apoptosis. RESULTS/ANTICIPATED RESULTS: ERMS tumor initiation in the tp53-/- background is observed in > 97% of animals whereas only <40% of wild-type animals develop ERMS. Additionally, tp53 is a potent suppressor of ERMS proliferation and its effect on apoptosis is minor. Next, we expressed either WT zebrafish or human TP53 in tp53-/- animals along with kRASG12D and both genes suppressed tumor initiation and growth. We co-expressed TP53C176F (found in two ERMS patients) and TP53P153del (identified in a patient with osteosarcoma in our clinic) in zebrafish ERMS, and find that the TP53C176F allele significantly suppressed tumor initiation with effects predominantly on enhanced apoptosis. However, the TP53P153del allele initiated tumors at similar frequency compared to tp53-/- animals but increased the initiation of tumors in the head musculature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Different TP53 alleles identified in patient tumors have very different effects on tumorigenesis in vivo and can respond differently to potentially therapeutic compounds. Thus, the type of precision modeling demonstrated here promises to help further define patient-specific TP53 biology and improve clinical strategies in the future.