The presence of caregivers or companions during clinical encounters influences the dynamics and outcomes of the encounters. Most prior studies of companions in clinical encounters focus on ...non-Hispanic White patients. However, there is generally lower-quality patient-physician communication during encounters with Black patients; these communication differences may contribute to racial health disparities. The purpose of the present study was to examine effects of the presence and active participation of companions on encounters between Black patients with cancer and non-Black oncologists.
This was a secondary analysis of data collected during a larger intervention study. Participants were Black patients with breast, colon, or lung cancer who had a treatment-discussion encounter with a participating non-Black medical oncologist. Video recordings of encounters were coded for patient, companion, and oncologist communication. After the encounter, patients reported perceptions of the recommended treatment; patients and oncologists reported perceptions of each other.
Data from 114 patients and 19 oncologists were included in analyses. Only 47% of patients brought a companion to the encounter. Oncologists spent more time with accompanied Black patients, used more patient-centered communication with them, and perceived them as having more social support compared with unaccompanied Black patients. Oncologists reported that accompanied patients asked more questions. When companions participated more actively in the encounter, oncologists used more patient-centered communication.
Bringing a companion to oncology appointments may be beneficial to Black patients because oncologists spend more time with patients, use more patient-centered communication, and perceive patients more positively, all of which may ultimately improve patient health and well-being outcomes.
Vascular cell adhesion molecule (VCAM)-1 expression may be coupled to redox-sensitive regulatory pathways, and iron may play a role in generation of reactive oxygen species that participate in these ...signaling pathways. To investigate the role of iron in TNFα-induced VCAM-1 gene expression, human dermal microvascular endothelial cells (HDMEC) were stimulated with TNFα in the presence of iron chelators and examined for expression of VCAM-1. The iron chelators dipyridyl (DP) and desferoxamine (DFO) inhibited VCAM-1 protein and mRNA induction in a concentration- and time-dependent manner. The induction of VCAM-1 was not inhibited by nonmetal binding reactive oxygen species (ROS) scavengers, implying a direct effect of iron in the expression of these adhesion molecules. The effect of iron was mediated at the level of gene transcription since pretreatment with DP abrogated the TNFα-mediated up-regulation of VCAM-1 heterogeneous nuclear RNA. Pretreatment of HDMEC with DP prior to TNFα treatment had no effect on p65 nuclear localization, DNA binding, or serine phosphorylation. DP pretreatment inhibited TNFα- and IFNγ-mediated interferon regulatory factor 1 (IRF-1) protein expression, although restoration of IRF-1 expression failed to reconstitute VCAM-1 expression. DP treatment also blocked VCAM-1 induction in human umbilical vein endothelium and blocked induction of a host of NF-kB activated genes in HDMEC including ICAM-1, IL-8, and tissue factor. IkBα, an NF-kB inducible and constitutively accessible gene not requiring chromatin remodeling for transcription, was not affected by DP treatment. These data suggest that iron plays a critical role in TNFα mediated VCAM-1 induction in HDMEC, and the target for iron effects may be IRF-1, NF-kB, and potentially chromatin remodeling.
Interferon regulatory factor-1 is a transcription factor that is linked to the expression of genes important in the initiation of the inflammatory response and the control of cell cycle. In this ...study, we determined that the generation of interferon regulatory factor-1 expression in human dermal microvascular endothelial cells was transcriptionally mediated by tumor necrosis factor-α or interferon-γ via iron-dependent pathways. The induction of interferon regulatory factor-1 protein and the upregulation of interferon regulatory factor-1 mRNA levels was inhibited when cells were pretreated with the iron chelators 2-2-dipyridyl or deferoxamine. This inhibition of interferon regulatory factor-1 expression was associated with loss of interferon regulatory factor-1 binding to the interferon-stimulated response element as assessed by electrophoretic mobility shift assay. Addition of exogenous iron with the iron chelator resulted in reconstitution of cytokine responsiveness, thus demonstrating iron as the target for the chelator effect. Both tumor necrosis factor-α and interferon-γ-induced interferon regulatory factor-1 gene transcription, as assessed by the measurement of unspliced, nascent, heterogeneous nuclear RNA, and treatment with iron chelators blocked tumor necrosis factor-α or interferon-γ mediated interferon regulatory factor-1 gene transcription. Iron was not essential, however, for the association of interferon regulatory factor-1 mRNA with polyribosomes, suggesting iron was not essential for interferon regulatory factor-1 protein translation. Through such inhibitory regulation on pro-inflammatory transcription factors, iron chelators may serve as anti-inflammatory agents.
Fear of cancer recurrence (FCR) is one of the most commonly-reported and distressing concerns of both cancer survivors (e.g., Allen, Savadatti, & Levy, 2009; Baker, Denniston, Smith, & West, 2005) ...and their partners (e.g., Hodges & Humphris, 2009; Mellon, Kershaw, Northouse, & Freeman-Gibb, 2007). Most research acknowledges that FCR is a multidimensional construct, consisting of at least cognitive and emotional components; however, few have actually distinguished between or assessed both of these components, despite their potentially unique implications for adjustment to cancer (Park, Cho, Blank, & Wortmann, 2013). The goal of the proposed study was to contribute to a better understanding of the definition and nature of FCR in both breast cancer patients and their partners by identifying its putative cognitive and emotional components (eFCR and cFCR, respectively), describing the longitudinal course of these components over the first year after diagnosis, and examining the ways in which the components of FCR may affect each other within a dyadic context. Results suggested that FCR is indeed better conceptualized as two separate but related cognitive and emotional factors. In both patients and their partners, levels of emotional FCR were found to decrease on average over the course of the first year post-diagnosis, while cognitive FCR exhibited a flat trajectory over this same time period. Within a dyadic context, it was found that an individual’s emotional FCR was not predictive of later eFCR in themselves or their partner, nor was it predictive of later perceived risk in their partner. However, within the same individual, lower perceived risk and greater eFCR each predicted later elevated perceived risk. Overall, results support the idea of FCR as a multidimensional construct and underscore the importance of distinguishing between emotional and cognitive components of FCR in future research.
One of the most prevalent and distressing concerns endorsed by breast cancer survivors is fear of cancer recurrence (FOR), and one of the most salient facets is the worry that a recurrence of cancer ...could cause one's death. The primary goal of the present study was to test the effects of a brief gratitude intervention on overall FOR and death-related FOR, with pursuit of meaningful goals examined as a potential mediator. Positive affect (PA) was also examined as both an outcome of the intervention and as a mediator of observed effects of the intervention on FOR. Sixty-seven women with early-stage breast cancer were randomly assigned to either a six-week online gratitude intervention or a six-week online control condition. Although the intervention did not predict changes in overall FOR, results revealed that patients in the gratitude intervention experienced a significant decrease in death-related FOR compared to the control condition. Moreover, this effect was partially mediated by goal pursuit. The gratitude intervention was also found to prevent a decline in PA observed in the control condition; however, PA did not mediate the effects of the intervention on death-related FOR. Overall, findings support the notion that gratitude promotes psychological adaptation to cancer by promoting the pursuit of meaningful goals and subsequently reducing death-related FOR.
Interferon regulatory factor-1 is a transcription factor that is linked to the expression of genes important in the initiation of the inflammatory response and the control of cell cycle. In this ...study, we determined that the generation of interferon regulatory factor-1 expression in human dermal microvascular endothelial cells was transcriptionally mediated by tumor necrosis factor-alpha or interferon-gamma via iron-dependent pathways. The induction of interferon regulatory factor-1 protein and the up-regulation of interferon regulatory factor-1 mRNA levels was inhibited when cells were pretreated with the iron chelators 2-2-dipyridyl or deferoxamine. This inhibition of interferon regulatory factor-1 expression was associated with loss of interferon regulatory factor-1 binding to the interferon-stimulated response element as assessed by electrophoretic mobility shift assay. Addition of exogenous iron with the iron chelator resulted in reconstitution of cytokine responsiveness, thus demonstrating iron as the target for the chelator effect. Both tumor necrosis factor-alpha and interferon-gamma-induced interferon regulatory factor-1 gene transcription, as assessed by the measurement of unspliced, nascent, heterogeneous nuclear RNA, and treatment with iron chelators blocked tumor necrosis factor-alpha or interferon-gamma mediated interferon regulatory factor-1 gene transcription. Iron was not essential, however, for the association of interferon regulatory factor-1 mRNA with polyribosomes, suggesting iron was not essential for interferon regulatory factor-1 protein translation. Through such inhibitory regulation on pro-inflammatory transcription factors, iron chelators may serve as anti-inflammatory agents.
The purpose of this study was to compare a technology‐based system, an in‐person behavioral weight loss intervention, and a combination of both over a 6‐month period in overweight adults. Fifty‐one ...subjects (age: 44.2 ± 8.7 years, BMI: 33.7 ± 3.6 kg/m2) participated in a 6‐month behavioral weight loss program and were randomized to one of three groups: standard behavioral weight loss (SBWL), SBWL plus technology‐based system (SBWL+TECH), or technology‐based system only (TECH). All groups reduced caloric intake and progressively increased moderate intensity physical activity. SBWL and SBWL+TECH attended weekly meetings. SBWL+TECH also received a TECH that included an energy monitoring armband and website to monitor energy intake and expenditure. TECH used the technology system and received monthly telephone calls. Body weight and physical activity were assessed at 0 and 6 months. Retention at 6 months was significantly different (P = 0.005) between groups (SBWL: 53%, SBWL+TECH: 100%, and TECH: 77%). Intent‐to‐treat (ITT) analysis revealed significant weight losses at 6 months in SBWL+TECH (−8.8 ± 5.0 kg, −8.7 ± 4.7%), SBWL (−3.7 ± 5.7 kg, −4.1 ± 6.3%), and TECH (−5.8 ± 6.6 kg, −6.3 ± 7.1%) (P < 0.001). Self‐report physical activity increased significantly in SBWL (473.9 ± 800.7 kcal/week), SBWL+TECH (713.9 ± 1,278.8 kcal/week), and TECH (1,066.2 ± 1,371 kcal/week) (P < 0.001), with no differences between groups (P = 0.25). The TECH used in conjunction with monthly telephone calls, produced similar, if not greater weight losses and changes in physical activity than the standard in‐person behavioral program at 6 months. The use of this technology may provide an effective short‐term clinical alternative to standard in‐person behavioral weight loss interventions, with the longer term effects warranting investigation.
Genomic studies have identified recurrent somatic mutations in acute leukemias. However, current murine models do not sufficiently encompass the genomic complexity of human leukemias. To develop ...preclinical models, we transplanted 160 samples from patients with acute leukemia (acute myeloid leukemia, mixed lineage leukemia, B-cell acute lymphoblastic leukemia, T-cell ALL) into immunodeficient mice. Of these, 119 engrafted with expected immunophenotype. Targeted sequencing of 374 genes and 265 frequently rearranged RNAs detected recurrent and novel genetic lesions in 48 paired primary tumor (PT) and patient-derived xenotransplant (PDX) samples. Overall, the frequencies of 274 somatic variant alleles correlated between PT and PDX samples, although the data were highly variable for variant alleles present at 0-10%. Seventeen percent of variant alleles were detected in either PT or PDX samples only. Based on variant allele frequency changes, 24 PT-PDX pairs were classified as concordant while the other 24 pairs showed various degree of clonal discordance. There was no correlation of clonal concordance with clinical parameters of diseases. Significantly more bone marrow samples than peripheral blood samples engrafted discordantly. These data demonstrate the utility of developing PDX banks for modeling human leukemia, and emphasize the importance of genomic profiling of PDX and patient samples to ensure concordance before performing mechanistic or therapeutic studies.
Alaska Native (AN) people have the world’s highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous ...data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or -promoting metabolites.
We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people.
A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes.
Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5 ± 3.1 compared with 47.2 ± 7.3 SEM µmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7 ± 4.2 compared with 11 ± 1.9 µmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps.
The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants.
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