Introduction/Purpose: Cardiovascular disease (CVD) is the leading cause of death worldwide, and in the United States alone, CVD causes nearly 840,000 deaths annually. Using functional magnetic resonance imaging (fMRI), a tool to assess brain activity, researchers have identified some brain-behavior connections and predicted several self-management behaviors. The purpose of this study was to examine the sample characteristics of individuals with CVD who participated in fMRI studies. Methods: A literature search was conducted in PubMed, CINAHL, and Scopus. No date or language restrictions were applied and research methodology filters were used. In October 2017, 1659 titles and abstracts were identified. Inclusion criteria were: (1) utilized an empirical study design, (2) used fMRI to assess brain activity, and (3) focused on patients with CVD-related chronic illness. Articles were excluded if they: were theory or opinion articles, focused on mental or neuropathic illness, included non-human samples, or were not written in English. After duplicates were removed (230), 1,429 titles and abstracts were reviewed based on inclusion criteria; 1,243 abstracts were then excluded. A total of 186 studies were reviewed in their entirety; after additional review, 142 were further excluded for not meeting the inclusion criteria. Forty-four articles met criteria and were included in the final review. An evidence table was created to capture the demographics of each study sample. Results: Ninety eight percent of the studies did not report the racial or ethnic composition of their sample. Most studies (66%) contained more men than women. Mean age ranged from 38 to 78 years; 77% reported mean age ≥50 years. The most frequently studied CVD was stroke (86%), while hypertension was studied the least (2%). Conclusion: Understanding brain-behavior relationships can help researchers and practitioners tailor interventions to meet specific patient needs. These findings suggest that additional studies are needed that focus on populations historically underrepresented in fMRI research. Researchers should thoughtfully consider diversity and purposefully sample groups by including individuals that are: women, from diverse backgrounds, younger, and diagnosed with a variety of CVD-related illnesses. Identifying and addressing these gaps by studying more representative samples will help healthcare providers reduce disparities and tailor interventions for all CVD populations.

Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme controls many cellular processes by phosphorylating both cytoplasmic and nuclear substrates. Here, we show that depletion or pharmacological inhibition of PAK1 down-regulated the expression of genes involved in the FA/BRCA pathway and compromised the ability of cells to repair DNA by Homologous Recombination (HR), promoting apoptosis and reducing colony formation. Combined inhibition of PAK1 and PARP in PAK1 overexpressing breast cancer cells had a synergistic effect, enhancing apoptosis, suppressing colony formation, and delaying tumor growth in a xenograft setting. Because reduced PAK1 activity impaired FA/BRCA function, inhibition of this kinase in PAK1 amplified and/or overexpressing breast cancer cells represents a plausible strategy for expanding the utility of PARP inhibitors to FA/BRCA-proficient cancers.

DNA methylation is a major epigenetic mechanism for gene silencing. Whereas methyltransferases mediate cytosine methylation, it is less clear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether an active demethylating activity is involved. Here, we show that either knockout or catalytic inactivation of the DNA repair enzyme thymine DNA glycosylase (TDG) leads to embryonic lethality in mice. TDG is necessary for recruiting p300 to retinoic acid (RA)-regulated promoters, protection of CpG islands from hypermethylation, and active demethylation of tissue-specific developmentally and hormonally regulated promoters and enhancers. TDG interacts with the deaminase AID and the damage response protein GADD45a. These findings highlight a dual role for TDG in promoting proper epigenetic states during development and suggest a two-step mechanism for DNA demethylation in mammals, whereby 5-methylcytosine and 5-hydroxymethylcytosine are first deaminated by AID to thymine and 5-hydroxymethyluracil, respectively, followed by TDG-mediated thymine and 5-hydroxymethyluracil excision repair.