The pattern of results suggests that preschoolers with SLI have deficits in executive functioning compared with typical peers, and deficits are not limited to verbal tasks. A significant linear relationship between group differences across executive function components supports the possibility of a hierarchical relationship between executive function skills.
Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower hindlimb oxygen consumption rates (OCRs), indicating depressed mitochondrial oxidative phosphorylation capacity in their skeletal muscle. We hypothesized that OCRs are lower in skeletal muscle mitochondria from IUGR fetuses, due to reduced electron transport chain (ETC) activity and lower abundances of tricarboxylic acid (TCA) cycle enzymes. IUGR sheep fetuses ( n = 12) were created with mid-gestation maternal hyperthermia and compared with control fetuses ( n = 12). At 132 ± 1 days of gestation, biceps femoris muscles were collected, and the mitochondria were isolated. Mitochondria from IUGR muscle have 47% lower State 3 (Complex I-dependent) OCRs than controls, whereas State 4 (proton leak) OCRs were not different between groups. Furthermore, Complex I, but not Complex II or IV, enzymatic activity was lower in IUGR fetuses compared with controls. Proteomic analysis ( n = 6/group) identified 160 differentially expressed proteins between groups, with 107 upregulated and 53 downregulated mitochondria proteins in IUGR fetuses compared with controls. Although no differences were identified in ETC subunit protein abundances, abundances of key TCA cycle enzymes [isocitrate dehydrogenase (NAD+) 3 noncatalytic subunit β (IDH3B), succinate-CoA ligase ADP-forming subunit-β (SUCLA2), and oxoglutarate dehydrogenase (OGDH)] were lower in IUGR mitochondria. IUGR mitochondria had a greater abundance of a hypoxia-inducible protein, NADH dehydrogenase 1α subcomplex 4-like 2, which is known to incorporate into Complex I and lower Complex I-mediated NADH oxidation. Our findings show that mitochondria from IUGR skeletal muscle adapt to hypoxemia and hypoglycemia by lowering Complex I activity and TCA cycle enzyme concentrations, which together, act to lower OCR and NADH production/oxidation in IUGR skeletal muscle.
Background
Latinos are currently the largest and fastest growing racial/ethnic group in the United States and have the lowest rates nationally of regular sources of primary care. The changing demographics of Latino populations have significant implications for the future health of the nation, particularly with respect to chronic disease. Community-based agencies and clinics alike have a long history of engaging community health workers (CHWs) to provide a broad range of tangible and emotional support strategies for Latinos with chronic diseases. In this paper, we present the protocol for a community intervention designed to evaluate the impact of CHWs in a Community-Clinical Linkage model to address chronic disease through innovative utilization of electronic health records (EHRs) and application of mixed methodologies. Linking Individual Needs to Community and Clinical Services (LINKS) is a 3-year, prospective matched observational study designed to examine the feasibility and impact of CHW-led Community-Clinical Linkages in reducing chronic disease risk and promoting emotional well-being among Latinos living in three U.S.-Mexico border communities.
Methods
The primary aim of LINKS is to create Community-Clinical Linkages between three community health centers and their respective county health departments in southern Arizona. Our primary analysis is to examine the impact of the intervention 6 to 12-months post program entry. We will assess chronic disease risk factors documented in the EHRs of participants versus matched non-participants. By using a prospective matched observational study design with EHRs, we have access to numerous potential comparators to evaluate the intervention effects. Secondary analyses include modeling within-group changes of extended research-collected measures. This approach enhances the overall evaluation with rich data on physical and emotional well-being and health behaviors of study participants that EHR systems do not collect in routine clinical practice.
Discussion
The LINKS intervention has practical implications for the development of Community-Clinical Linkage models. The collaborative and participatory approach in LINKS illustrates an innovative evaluation framework utilizing EHRs and mixed methods research-generated data collection.
Trial registration
This study protocol was retrospectively registered, approved, and made available on Clinicaltrials.gov by
NCT03787485
as of December 20, 2018.
Electronic supplementary material
The online version of this article (10.1186/s12889-019-6725-1) contains supplementary material, which is available to authorized users.
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