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Background: Higher diet quality scores are associated with a lower risk for many chronic diseases and all-cause mortality; however, it is unclear if diet quality is associated with aging biology., Objective: This study aimed to examine the association between diet quality and a measure of biological aging known as epigenetic aging., Design: A cross-sectional data analysis was used to examine the association between three diet quality scores based on self-reported food frequency questionnaire data and five measures of epigenetic aging based on DNA methylation (DNAm) data from peripheral blood., Participants/setting: This study included 4,500 postmenopausal women recruited from multiple sites across the United States (1993-98), aged 50 to 79 years, with food frequency questionnaire and DNAm data available from the Women's Health Initiative baseline visit., Main Outcome Measures: Five established epigenetic aging measures were generated from HumanMethylation450 Beadchip DNAm data, including AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, AgeAccelGrim, and DunedinPACE., Statistical Analyses Performed: Linear mixed models were used to test for associations between three diet quality scores (Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores) and epigenetic aging measures, adjusted for age, race and ethnicity, education, tobacco smoking, physical activity, Women's Health Initiative substudy from which DNAm data were obtained, and DNAm-based estimates of leukocyte proportions., Results: Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores were all inversely associated with AgeAccelPheno, AgeAccelGrim, and DunedinPACE (P < 0.05), with the largest effects with DunedinPACE. A one standard deviation increment in diet quality scores was associated with a decrement (β ± SE) in DunedinPACE z score of -0.097 ± 0.014 (P = 9.70 x 10 -13 ) for Healthy Eating Index, -0.107 ± 0.014 (P = 1.53 x 10 -14 ) for Dietary Approaches to Stop Hypertension, and -0.068 ± 0.013 (P = 2.31 x 10 -07 ) for the alternate Mediterranean diet., Conclusions: In postmenopausal women, diet quality scores were inversely associated with DNAm-based measures of biological aging, particularly DunedinPACE., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association of total energy intake (EI) with all-cause mortality is uncertain as are the dependencies of this association on age and weight change history., Objectives: To identify an EI biomarker suitable for use in epidemiologic association studies and to study EI associations with total mortality in a Women's Health Initiative (WHI) cohort of postmenopausal United States females (1993-present)., Methods: EI biomarkers were developed based on doubly labeled water (DLW) total energy expenditure (TEE) and weight variation during the 2-wk DLW protocol period using the energy balance method in an embedded feeding study (n = 153). This along with 2 earlier WHI nutrition biomarker studies having TEE assessments (n = 1131 total), with 14.6 y (median) follow-up, constituted a prospective cohort for the study of EI and all-cause mortality., Results: An empirical biomarker for log(EI) was developed that had a correlation of 0.73 with log(feeding study-consumed EI). The overall association between EI and mortality was nonsignificant. The association, however, depended on age (P = 0.009), with lower EI associated with lower mortality at younger ages, and also on preceding weight change history (P = 0.03). Among participants with stable or increasing weight, mortality hazard ratios (95% confidence intervals [CIs]) for a 12% lower EI were 0.66 (95% CI: 0.51, 0.87) at age 60, 0.84 (95% CI: 0.72, 0.98) at age 70, and 1.06 (95% CI: 0.87, 1.29) at age 80. Corresponding values for participants having preceding weight loss were 0.83 (95% CI: 0.61, 1.12) at age 60, 1.05 (95% CI: 0.87, 1.26) at age 70, and 1.33 (95% CI: 1.08, 1.63) at age 80. A previously considered EI biomarker, using a theoretical model for variation in body fat and fat-free mass components over time, gave similar results following rescaling., Conclusions: Lower EI is associated with lower all-cause mortality among younger postmenopausal females with stable or increasing weight and with higher mortality among older females with weight loss. This study was registered with clinicaltrials.gov as NCT00000611., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Purpose: Long-term survivors of brain irradiation can experience irreversible injury and cognitive impairment. T1-weighted and diffusion tensor magnetic resonance imaging (MRI) are used to evaluate brain volume and white matter (WM) microstructure in neurodevelopmental and neurodegenerative conditions. The goal of this study was to evaluate the long-term effects of single-dose total-body irradiation (TBI) or TBI with 5% partial-body sparing on brain volumetrics and WM integrity in macaques., Methods and Materials: We used MRI scans from a cohort of male rhesus macaques (age range, 3.6-22.8 years) to compare global and regional brain volumes and WM diffusion in survivors of TBI (T1-weighted, n = 137; diffusion tensor imaging, n = 121; dose range, 3.5-10 Gy) with unirradiated controls (T1-weighted, n = 48; diffusion tensor imaging, n = 38)., Results: In all regions of interest, radiation affected age-related changes in fractional anisotropy, which tended to increase across age in both groups but to a lesser extent in the irradiated group (interaction P < .01). Depending on the region of interest, mean diffusivity decreased or remained the same across age in unirradiated animals, whereas it increased or did not change in irradiated animals. The increases in mean diffusivity were driven by changes in radial diffusivity, which followed similar trends across age. Axial diffusivity did not differ by irradiation status. Age-related changes in relative volumes in controls reflected normal trends in humans, with increasing WM and decreasing gray matter until middle age. Cerebrospinal fluid (CSF) volume did not differ across age in controls. WM volume was lower and CSF volume was higher in young irradiated macaques. WM volume was similar between groups, and CSF volume lower in older irradiated macaques. Gray matter volume was unaffected by radiation., Conclusions: TBI results in delayed WM expansion and long-term disruption of WM integrity. Diffusion changes suggest that myelin injury in WM is a hallmark of late-delayed radiation-induced brain injury., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Single-agent checkpoint inhibition is effective in a minority of patients with platinum-refractory urothelial carcinoma; therefore, the efficacy of combining low-dose paclitaxel with pembrolizumab was tested., Materials and Methods: This was a prospective, single-arm phase II trial with key inclusion criteria of imaging progression within 12 months of platinum therapy and Eastern Cooperative Oncology Group ≤1. Treatment was pembrolizumab 200 mg day 1 and paclitaxel 80 mg/m2 days 1 and 8 of a 21-day cycle for up to eight cycles unless progression or unacceptable adverse events (AE). The primary endpoint was overall response rate (ORR) with overall survival (OS), 6-month progression-free survival (PFS), and safety as key secondary endpoints. Change in circulating immune cell populations, plasma, and urinary miRs were evaluated., Results: Twenty-seven patients were treated between April 2016 and June 2020, with median follow-up of 12.4 months. Baseline median age was 68 years, with 81% men and 78% non-Hispanic White. ORR was 33% by intention to treat and 36% in imaging-evaluable patients with three complete responses. Six-month PFS rate was 48.1% [95% confidence interval (CI): 28.7-65.2] and median OS 12.4 months (95% CI: 8.7 months to not reached). Common ≥ grade 2 possibly-related AEs were anemia, lymphopenia, hyperglycemia, and fatigue; grade 3/4 AEs occurred in 56%, including two immune-mediated AEs (pneumonitis and nephritis). Responding patients had a higher percentage of circulating CD4+IFNγ+ T cells. Levels of some miRs, including plasma miR 181 and miR 223, varied in responders compared with nonresponders., Conclusions: The addition of low-dose paclitaxel to pembrolizumab is active and safe in platinum-refractory urothelial carcinoma., Significance: We found that combining pembrolizumab with low-dose paclitaxel may be effective in patients with urothelial carcinoma progressing on platinum chemotherapy, with favorable safety profiles., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Purpose/objectives: The purpose of this study was to transcreate a manualized cognitive-behavioral therapy (CBT) intervention to address depression and anxiety among Hispanic cancer survivors., Design/research Approach: Stakeholders reviewed the CBT workbook for language, content, and cultural relevance. We designed semi-structured interview guides to elicit intervention feedback., Sample/participants: Stakeholder participants were Hispanic cancer survivors ( n  = 4), bilingual mental health providers ( n  = 2), and oncology professionals ( n  = 4)., Methods: Transcreation was conducted by initial translation of the workbook followed by incorporation of stakeholder feedback. A bilingual (Spanish and English) interviewer conducted stakeholder interviews. The study team discussed themes/suggestions before refining the workbook., Findings: Stakeholders reported enthusiasm for the intervention. We gathered significant feedback regarding wording, images, and resources for the workbook., Conclusion: Development of culturally appropriate mental health resources for Hispanic cancer survivors is critical., Implications for Psychosocial Providers or Policy: By broadening research on psychosocial care to the Hispanic population, we increase the reach of evidence-based psychological care. Future research should fully evaluate the adapted CBT intervention among Hispanic survivors.

Purpose: Improved management of pain and co-morbid symptoms (sleep disturbances, psychological distress) among women undergoing surgery for suspected gynecologic malignancies may reach a population vulnerable to chronic pain., Participants: Women undergoing surgery for a suspected gynecologic malignancy., Method: We conducted a pilot randomized controlled trial of eHealth Mindful Movement and Breathing (eMMB) compared to an empathic attention control (AC). Semi-structured interviews were conducted by telephone ( n  = 23), recorded, transcribed, coded, and analyzed using thematic analysis., Findings: Participants reported overall high acceptability such that all would recommend the study to others. Positive impacts of practicing eMMB included that it relieved tension, facilitated falling asleep, and decreased pain. Participants also reported high adherence to self-directed eMMB and AC writing practices and described facilitators and barriers to practicing., Conclusions: This qualitative feedback will inform future research to assess the efficacy of eMMB for reducing pain and use of remotely-delivered interventions more broadly., Clinical Trial Registration Number: NCT03681405.