Adding COVID to cancer: does cancer status influence COVID-19 infection preventive behaviors?

Introduction: A better understanding of how to promote disease mitigation and prevention behaviors among vulnerable populations, such as cancer survivors, is needed. This study aimed to determine patterns of and factors associated with COVID-19-related preventive behaviors among cancer survivors and assess whether the COVID-19 preventive behaviors of cancer survivors differ from the general population. Methods: In June 2020, an online survey of adults (N = 897) assessed predictors of COVID-19-related preventive behaviors, including socio-demographics, COVID-19 beliefs and perceptions (Health Belief Model [HBM] variables), and cancer statuses (cancer survivors currently in treatment, cancer survivors not currently in treatment, and individuals with no history of cancer). An average score of respondent engagement in eight preventive behaviors was calculated. Differences in HBM variables and preventive behaviors by cancer status were assessed using ANCOVAs. Hierarchical multiple regression analyzed associations among socio-demographics, HBM constructs, cancer statuses, and engagement in COVID-19 preventive behaviors. Results: Participants reported engaging in 3.5 (SD = 0.6) preventive behaviors. Cancer survivors not in treatment engaged in preventive behaviors significantly less than the comparison group. In the final adjusted model, after adding COVID-19 beliefs and perceptions, cancer status was no longer significant. All HBM constructs except perceived susceptibility were significant predictors of preventive behaviors. Conclusions: COVID-19 beliefs and perceptions were more robust predictors preventive behaviors than cancer status. Nonetheless, public health organizations and practitioners should communicate the risk and severity of infection among cancer survivors and emphasize the need to engage in protective behaviors for COVID-19 and other infectious diseases with this vulnerable population.

Cancer Prevention Among Firefighters: Examining Lifestyle, Screening Behavior, and Beliefs.

BACKGROUND: Firefighters are at increased risk of developing cancer due to occupational exposures, but they may also face increased risk due to their lifestyle, such as the quality of their diet and physical activity. Cancer beliefs and screening behavior could also influence their cancer risk. The current study aimed to identify individual differences associated with lifestyle behaviors, cancer screening, and cancer beliefs among firefighters; to describe the strategies firefighters use to adapt to their work schedule; and to describe topics firefighters believe are the most important to address in their workplace. METHODS: Career firefighters (N = 171) in a medium-sized U.S. city completed an online survey. FINDINGS: Logistic regression analyses identified age, education, racial identity, years of fire service, perceived stress, and rank as predictors of responses to items addressing cancer screening, lifestyle behaviors, and cancer beliefs. Although results varied, age, education, and racial identity were associated with most of the outcomes. Strategies related to sleep such as getting the right amount and napping, exercise, and getting family/roommate support were selected as the top adaptive strategies for work. Sleep, mental health/well-being, and work-life balance were selected most often as the most important topics to address in the fire service, with topics related to reducing occupational exposures receiving less attention. CONCLUSIONS/APPLICATION TO PRACTICE: The findings suggest individual differences, such as age, education, and racial identity, should be considered when developing occupational health interventions for firefighters. Interventions related to mental health, work-life balance, and sleep may be desired most by those in the fire service.

Tobacco exposures are associated with health care utilization (HCU) and health care costs in pregnant persons and their newborn babies.

INTRODUCTION: Identifying health care utilization and costs associated with active and passive smoking during pregnancy could help improve health management strategies. METHODS: Data are from the Newborn Epigenetics STudy (NEST), a birth cohort enrolled from 2005-2011 in Durham and adjacent counties in North Carolina, United States. Participants included those for whom prenatal serum samples were assayed and for whom administrative data were obtainable (N=1,045). Zero-inflated Poisson (ZIP) regression models were used to assess associations between cotinine, adjusted for covariates (e.g., race and ethnicity, age at delivery, cohabitation status, education), and health care utilization outcomes. Generalized linear regression models were used to estimate average total charges. Simulation models were conducted to determine the economic benefits of reducing SHS and smoking during pregnancy. RESULTS: Increasing levels of cotinine were positively associated with parent's number of ED visits (coefficient(b)=0.0012, standard error (SE)=0.0002; P<.001), the number of ICU hours (b=0.0079, SE=0.0025; P=.002)), time spent in the ICU (b=0.0238, SE=0.0020, P<.001), and the number of OP visits (b=0.0003, SE=0.0001; P<.001). For infants, higher cotinine levels were associated with higher number of ED (b=0.0012, SE=0.0004; P=.005), ICU (b=0.0050, SE=0.001; P<.001), and OP (b=0.0006, SE=0.0002; P<.001) visits and longer time spent in the ED (b=0.0025, SE=0.0003; P<.001), ICU (b=0.0005, SE=0.0001; P<.001), and IP (b=0.0020, SE=0.0002; P<.001). Simulation results showed that a 5% reduction in smoking would correspond to a potential median cost savings of $150,533 from ED visits of parents and infants. CONCLUSION: Our findings highlight the importance of smoke exposure cessation during pregnancy to reduce health care utilization and costs for both parents and infants. IMPLICATIONS: This study reinforces the importance of reducing smoking and secondhand smoke exposure during pregnancy. Focusing on expanding cessation services to this group could help reduce morbidities observed within this population. Furthermore, there is the potential for health care costs savings to health care systems, especially to those with high delivery numbers. These cost savings are represented by potential reductions in ED, OP, and ICU hours and visits.

Potential imaging targets in primary head and neck squamous cell carcinoma and lymph node metastases.

PURPOSE: To investigate glycoprotein nonmetastatic melanoma protein B (GPNMB) and vascular endothelial growth factor (VEGF) as potential fluorescent imaging markers by comparing their protein expression to epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: Thirty-eight paired samples of untreated head and neck squamous cell carcinoma (HNSCC) primary tumours (PT) and corresponding synchronous lymph node metastases (LNM) were selected. After immunohistochemical staining, expression was assessed and compared by the percentage of positive tumour cells. Data were analysed using the Mann-Whitney test, effect sizes (ESr) and Spearman's correlation coefficient (r). RESULTS: GPNMB expression was observed in 100 % of PT, and median 80 % (range 5-100 %) of tumour cells, VEGF in 92 % and 60 % (0-100 %), EGFR in 87 % and 60 % (0-100 %) respectively. In corresponding LNM, GPNMB expression was observed in 100 % of LNM and median 90 % (20-100 %) of tumour cells, VEGF in 87 % and 65 % (0-100 %), and EGFR in 84 % and 35 % (0-100 %). A positive correlation was found between expression in PT and LNM for GPNMB (r = 0.548) and EGFR (r = 0.618) (p < 0.001), but not for VEGF (r = -0.020; p = 0.905). GPNMB expression was present in a higher percentage of tumour cells compared to EGFR in PT (p = 0.015, ESr = -0.320) and in LNM (p < 0.001, ESr = -0.478), while VEGF was not (p = 1.00, ESr = -0.109 and - 0.152, respectively). CONCLUSION: GPNMB expression is higher than EGFR in untreated HNSCC PT and corresponding LNM, while VEGF expression is comparable to EGFR. GPNMB is a promising target for fluorescent imaging in HNSCC.

Rural-specific identity and associations with lifestyle behaviors and well-being among rural cancer survivors.

BACKGROUND: Disparities in rural cancer survivors' health outcomes are well-documented, yet the role of sociocultural aspects of rurality, such as rural identity, attitudes toward rurality, and social standing on health beliefs and behaviors remain unclear. This study aimed to address these gaps. METHODS: Rural cancer survivors (N = 188) completed a mailed/online survey. Regression analyses identified relationships among rural identity, negative attitudes toward rurality, and social standing with health outcomes, quality of life, cancer fatalism, and cancer information overload. RESULTS: Higher rural identity was associated with believing everything causes cancer (OR = 1.58, p = 0.048), believing "there's not much you can do to lower your chances of getting cancer" (OR = 2.22, p = 0.002), and higher odds of being overloaded with cancer information (OR = 2.05, p  = 0.008). Negative attitudes toward rurality was linked with higher levels of perceived stress (B = 0.83, p = 0.001), and chronic pain (OR = 1.47, p = 0.039). Higher subjective social status was associated with perceived social support (B = 0.09, p = 0.016), better overall health (B = 0.13, p < 0.001), lower levels of perceived stress (B = -0.38, p = 0.007), and chronic pain (OR = 0.80, p = 0.027). CONCLUSION: Sociocultural factors of rurality were associated with indicators of quality of life, cancer fatalism, and information overload. Further exploration of the underlying mechanisms that drive these associations can help improve intervention targets for rural cancer survivors.

The IRG1-itaconate axis protects from cholesterol-induced inflammation and atherosclerosis.

Atherosclerosis is fueled by a failure to resolve lipid-driven inflammation within the vasculature that drives plaque formation. Therapeutic approaches to reverse atherosclerotic inflammation are needed to address the rising global burden of cardiovascular disease (CVD). Recently, metabolites have gained attention for their immunomodulatory properties, including itaconate, which is generated from the tricarboxylic acid-intermediate cis-aconitate by the enzyme Immune Responsive Gene 1 (IRG1/ACOD1). Here, we tested the therapeutic potential of the IRG1-itaconate axis for human atherosclerosis. Using single-cell RNA sequencing (scRNA-seq), we found that IRG1 is up-regulated in human coronary atherosclerotic lesions compared to patient-matched healthy vasculature, and in mouse models of atherosclerosis, where it is primarily expressed by plaque monocytes, macrophages, and neutrophils. Global or hematopoietic Irg1-deficiency in mice increases atherosclerosis burden, plaque macrophage and lipid content, and expression of the proatherosclerotic cytokine interleukin (IL)-1ß. Mechanistically, absence of Irg1 increased macrophage lipid accumulation, and accelerated inflammation via increased neutrophil extracellular trap (NET) formation and NET-priming of the NLRP3-inflammasome in macrophages, resulting in increased IL-1ß release. Conversely, supplementation of the Irg1-itaconate axis using 4-octyl itaconate (4-OI) beneficially remodeled advanced plaques and reduced lesional IL-1ß levels in mice. To investigate the effects of 4-OI in humans, we leveraged an ex vivo systems-immunology approach for CVD drug discovery. Using CyTOF and scRNA-seq of peripheral blood mononuclear cells treated with plasma from CVD patients, we showed that 4-OI attenuates proinflammatory phospho-signaling and mediates anti-inflammatory rewiring of macrophage populations. Our data highlight the relevance of pursuing IRG1-itaconate axis supplementation as a therapeutic approach for atherosclerosis in humans.

Initial Safety and Feasibility Results From a Phase 1, Diagnose-and-Treat Trial of Neoadjuvant Intratumoral Cisplatin for Stage IV NSCLC.

Neoadjuvant intratumoral cisplatin has the potential to generate substantial cytotoxicity and immune priming within the tumor environment, while minimizing systemic, off-target, adverse events. We initiated a phase 1A, 3+3 dose-ranging study of neoadjuvant, intratumoral cisplatin, delivered through endobronchial ultrasound bronchoscopy, in the same procedure as the initial diagnosis. There were no dose-limiting toxicity identified at the 20mg level.

Identification of new head and neck squamous cell carcinoma molecular imaging targets.

OBJECTIVES: Intraoperative fluorescence imaging (FI) of head and neck squamous cell carcinoma (HNSCC) is performed to identify tumour-positive surgical margins, currently using epidermal growth factor receptor (EGFR) as imaging target. EGFR, not exclusively present in HNSCC, may result in non-specific tracer accumulation in normal tissues. We aimed to identify new potential HNSCC FI targets. MATERIALS AND METHODS: Publicly available transcriptomic data were collected, and a biostatistical method (Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling) was applied. TACNA-profiling captures downstream effects of CNAs on mRNA levels, which may translate to protein-level overexpression. Overexpressed genes were identified by comparing HNSCC versus healthy oral mucosa. Potential targets, selected based on overexpression and plasma membrane expression, were immunohistochemically stained. Expression was compared to EGFR on paired biopsies of HNSCC, adjacent macroscopically suspicious mucosa, and healthy mucosa. RESULTS: TACNA-profiling was applied on 111 healthy oral mucosa and 410 HNSCC samples, comparing expression levels of 19,635 genes. The newly identified targets were glucose transporter-1 (GLUT-1), placental cadherin (P-cadherin), monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2), and were evaluated by IHC on samples of 31 patients. GLUT-1 was expressed in 100 % (median; range: 60-100 %) of tumour cells, P-cadherin in 100 % (50-100 %), EGFR in 70 % (0-100 %), MCT-1 in 30 % (0-100 %), and NG2 in 10 % (0-70 %). GLUT-1 and P-cadherin showed higher expression than EGFR (p < 0.001 and p = 0.015). CONCLUSIONS: The immunohistochemical confirmation of TACNA-profiling results showed significantly higher GLUT-1 and P-cadherin expression than EGFR, warranting further investigation as HNSCC FI targets.

Narrow band imaging reveals field cancerisation undetected by conventional white light: Optical diagnosis versus histopathology.

OBJECTIVE: To assess whether narrow band imaging (NBI) detects fields of cancerisation around suspicious lesions in the upper aerodigestive tract, which were undetected by white light imaging (WLI). METHODS: In 96 patients with laryngeal and pharyngeal lesions suspicious for malignancy, 206 biopsies were taken during laryngoscopy: 96 biopsies of suspicious lesions detected by both WLI and NBI (WLI+/NBI+), 60 biopsies adjacent mucosa only suspicious with NBI (WLI-/NBI+), and 46 biopsies of NBI and WLI unsuspicious mucosa (WLI-/NBI-) as negative controls. Optical diagnosis according to the Ni-classification was compared with histopathology. RESULTS: Signs of (pre)malignancy were found in 88% of WLI+/NBI+ biopsies, 32% of WLI-/NBI+ biopsies and 0% in WLI-/NBI- (p < .001). In 58% of the WLI-/NBI+ mucosa any form of dysplasia or carcinoma was detected. CONCLUSION: The use of additional NBI led to the detection of (pre)malignancy in 32% of the cases, that would have otherwise remained undetected with WLI alone. This highlights the potential of NBI as a valuable adjunct to WLI in the identification of suspicious lesions in the upper aerodigestive tract.

Snapping Wrist From Bowstringing of the Digital Flexors After Carpal Tunnel Release: A Case Report.

Symptomatic bowstringing of digital flexor tendons is a rare complication of carpal tunnel release (CTR). Two weeks after open CTR, a 47-year-old man with severe carpal tunnel syndrome had relief of his preoperative median paresthesia but complained of new-onset painful snapping of the wrist and transient ulnar paresthesia occurring with wrist dorsiflexion and concomitant digital flexion. Physical examination localized the audible snapping to the hook of hamate (HOH) where manual pressure eliminated the wrist motion-induced snapping and the associated ulnar paresthesia. Wrist radiographs showed stage III scapholunate advanced collapse (SLAC) with marked palmar subluxation of the lunate. Wrist magnetic resonance imaging revealed palmar and ulnar subluxation of the digital flexors over the HOH due to the mass effect of the palmarly displaced lunate and the chronic carpal malalignment. The snapping wrist and accompanying ulnar paresthesia resolved after HOH excision, and no additional treatment for the asymptomatic SLAC wrist deformity was required. Satisfactory clinical outcome was observed at 5-year follow-up.

Initial evidence of the acute effect of electronic nicotine delivery system use on energy intake.

Previous work has aimed to disentangle the acute effects of nicotine and smoking on appetite with mixed findings. Electronic nicotine delivery systems (ENDS) have yet to be examined in this regard despite evidence of use for weight control. The present study tested the influence of an ENDS on acute energy intake and associated subjective effects. Participants (n = 34; 18-65 years) with current ENDS use completed two randomly ordered clinical lab sessions after overnight abstinence from tobacco/nicotine/food/drinks (other than water). Sessions differed by the product administered over 20 min: active (20 puffs of a JUUL ENDS device; 5% nicotine tobacco-flavored pod) or control (access to an uncharged JUUL with an empty pod). About 40 min after product administration, participants were provided an ad lib buffet-style meal with 21 food/drink items. Subjective ratings were assessed at baseline, after product use, and before/after the meal. Energy intake (kcal) was calculated using pre-post buffet item weights. Repeated measures analyses of variance and pairwise comparisons were used to detect differences by condition and time (α < .05). Mean ± standard error of the mean energy intake did not differ significantly between active (1011.9 ± 98.8 kcal) and control (939.8 ± 88.4 kcal; p = .108) conditions. Nicotine abstinence symptoms significantly decreased after the active condition, while satiety significantly increased. Following the control condition, satiety remained constant while hunger significantly increased relative to baseline. Findings indicate that acute ENDS use did not significantly impact energy intake, but there was an ENDS-associated subjective increase in satiety and relative decrease in hunger. Results support further investigation of ENDS on appetite. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Barriers and Facilitators of Colorectal Cancer Screening During the COVID-19 Pandemic.

BACKGROUND: COVID-19 introduced new barriers to health care including cancer screenings. This study evaluated the role of pandemic- and copay-related barriers to colonoscopy and the extent to which home-based testing methods were utilized. METHODS: A cross-sectional survey assessed colorectal cancer (CRC) attitudes and screening early in the COVID-19 pandemic. RESULTS: Respondents (342; 50.37% female) were 62.32 (SD = 6.87) years old. Roughly half were White/Caucasian (329; 48.45%); 29.75% were Black/African American (202); and 21.80% were another race (148). Roughly two-thirds were up-to-date with CRC screening (459; 67.59%). In an adjusted model, those with a higher agreement that concerns about COVID-19 delayed scheduling their colonoscopy (OR = .79; 95% CI: .08, .63; P = .045) and concerns about copays delayed scheduling their colonoscopy (OR = .73; 95% CI: .73, .57; P = .02) were less likely to be up-to-date on screening. In another adjusted model, those screened during the pandemic were significantly more likely to be screened via an at-home test (OR = 10.93; 95% CI: 5.95, 20.27; P < .001). DISCUSSION: During the COVID-19 pandemic, screening copay-related concerns persisted and were significantly higher among those not up-to-date with CRC screening. Increased at-home testing and addressing copay barriers may increase CRC screening adherence now and in future infectious disease outbreaks.

Advertising Exposure From Online and Offline Sources and Youth Tobacco Use: Findings From the Adolescents, Place, and Behavior Study.

INTRODUCTION: Tobacco use among adolescents is an ongoing public health concern. Youth tobacco use has been associated with advertising, from both online sources and retail environments. AIMS AND METHODS: This study examined associations between exposure to tobacco advertisements from tobacco retail outlets (TROs), internet, and social media sources and ever tobacco use among adolescents. Data were obtained from youth, aged 11-17 years (N = 401) from Richmond, VA. Bayesian index and group index models were fitted to estimate indices of exposure to (1) social media use, (2) tobacco ads on social media, and (3) TRO store visits and their association with ever tobacco use. The most important components of the exposure indices were also determined based on the index component weights from the Bayesian index models. RESULTS: In Bayesian index models of single exposures, each exposure index was significantly associated with tobacco use. In the best-fitting model, social media tobacco ads (odds ratio [OR] = 2.2; 95% credible interval [CI]: 1.2, 4.5) and TRO store visits (OR = 1.6; 95% CI: 1.1, 2.3) were significantly associated with ever tobacco use, as was older age (OR = 1.4; 95% CI: 1.2, 1.8). Index component weights revealed Snapchat ad frequency as the most important platform in the social media index and convenience stores as the most important type of store in the TRO index. CONCLUSIONS: Exposure to pro-tobacco advertisements on social media and visits to TROs are associated with adolescent ever tobacco use. Results provide support for policies that would restrict the promotion of tobacco products at TROs and on social media. Tobacco regulations and interventions targeting convenience stores and Snapchat may be warranted to reduce youth tobacco use. IMPLICATIONS: Current evidence provide support for policies that would restrict the promotion of tobacco products at TROs and on social media. Findings suggest that regulations and interventions that specifically target advertisements in convenience stores and on Snapchat may be currently warranted to reduce youth tobacco use.

Elbow stiffness: Interview with professor Bernard Morrey.

Stiff elbow is a complex condition whose diagnosis and management are sometimes quite a challenge. Compared to the other joints, the elbow is disproportionately affected by loss of motion following trauma or surgery. It is unclear why the elbow tends to develop stiffness; its anatomical complexity, namely the presence of three highly congruent joints in the same capsule and synovial space, the tautness of the lateral and medial collateral ligaments through the whole range of motion, and the very close relationship among tendons, muscles, and skin 2 may account for this characteristic. In a stiff elbow, it is critical to assess the possible involvement of articular and periarticular tissues, particularly the degree of preservation of the articular surfaces and joint congruency. Morrey et al have classified post-traumatic stiff elbow into three types: 1) extrinsic contracture, which involves the soft tissue around the joint (capsule, ligaments, muscles) and heterotopic ossification across the joint, 2) intrinsic contracture, secondary to intra-articular fractures that have altered the anatomy of the articular surface, and 3) mixed contracture, combining intrinsic and extrinsic contracture. In the preoperative clinical assessment, we assume capsule contracture to be present in all patients with a stiff elbow. Two main associated lesions can affect prognosis and surgical management: heterotopic ossification and an altered bone joint anatomy. According to Morrey et al, most activities of daily living can be accomplished within an arc of motion from 30° to 130° in extension and flexion and of 50° in pronation and supination. The elbow arc of motion is not compensated for by the wrist and shoulder, thus loss of extension impairs the use of the hand in the space around the body and loss of flexion limits its use for grooming and self-care. The elbow should carefully be tested for deformity of the axial bone alignment (varus and valgus deformity) and rotational stability. Several treatment options are available for stiff elbow, from conservative management with a dedicated rehabilitation program to surgical treatment and from arthroscopic capsulectomy to joint replacement.

The influence of clinical experience on reliable evaluation of pharyngeal and laryngeal lesions: comparison of high-definition laryngoscopy using narrow band imaging with fibre-optic laryngoscopy.

BACKGROUND: Fibre-optic laryngoscopy is still widely used in daily clinical practice; however, high-definition laryngoscopy using narrow band imaging could be more reliable in characterising pharyngeal and laryngeal lesions. METHODS: Endoscopic videos were assessed in a tertiary referral hospital by 12 observers with different levels of clinical experience. Thirty pairs of high-definition laryngoscopy with narrow band imaging and fibre-optic laryngoscopy videos were judged twice, with an interval of two to four weeks, in a random order. Inter- and intra-observer reliability, sensitivity and specificity were calculated in terms of detecting a malignant lesion and a specific histological entity, for beginners, trained observers and experts. RESULTS: Using high-definition laryngoscopy with narrow band imaging, inter-observer reliability for detecting malignant lesions increased from moderate to substantial in trained observers and experts (high-definition laryngoscopy with narrow band imaging κ = 0.66 and κ = 0.77 vs fibre-optic laryngoscopy κ = 0.51 and κ = 0.56, for trained observers and experts respectively) and sensitivity increased by 16 per cent. CONCLUSION: Inter-observer reliability increased with the level of clinical experience, especially when using high-definition laryngoscopy with narrow band imaging.

Neonatal and Infant Lung Disorders: Glossary, Practical Approach, and Diagnoses.

A multitude of lung disorders ranging from congenital and genetic anomalies to iatrogenic complications can affect the neonate or the infant within the first year of life. Neonatal and infant chest imaging, predominantly by plain radiography and computed tomography, is frequently employed to aid in diagnosis and management; however, these disorders can be challenging to differentiate due to their broad-ranging, and frequently overlapping radiographic features. A systematic and practical approach to imaging interpretation which includes recognition of radiologic patterns, utilization of commonly accepted nomenclature and classification, as well as interpretation of imaging findings in conjunction with clinical history can not only assist radiologists to suggest the diagnosis, but also aid clinicians in management planning. The contents of this article were endorsed by the leadership of both the World Federation of Pediatric Imaging (WFPI), and the International Society of Pediatric Thoracic Imaging (ISPTI).

Association between allostatic load and breast cancer risk: a cohort study.

BACKGROUND: Allostatic load (AL) reflects the collective load of chronic stress during lifetime. Previous studies have shown that higher AL is associated with poor clinical outcomes among breast cancer patients. However, the relationship between AL and breast cancer risk is still unclear. METHODS: To fill the gap, we analyzed the association between AL and the development of breast cancer in 181,455 women identified from the UK Biobank. RESULTS: During the follow-up from 2006 to 2020, 5,701 women were diagnosed with incident breast cancer. Significantly higher AL was observed among incident breast cancer cases than all study participants (mean: 2.77 vs. 2.63, P < 0.01). Univariate Cox regression analysis indicated the risk of breast cancer was increased by 5% per one AL unit increase (hazard ratio (HR) = 1.05, 95% confidence interval (CI) 1.04, 1.07). In multivariate analyses, after adjusting demographics, family history of breast cancer, reproductive factors, socioeconomic status, lifestyle factors, and breast cancer polygenic risk score (PRS), the significant association remained (HR = 1.05, 95%CI 1.03, 1.07). The significant relationship was further confirmed in the categorical analysis. Compared with women in the low AL group (AL: 0 ~ 2), those in the high AL group (AL: 3 ~ 11) had a 1.17-fold increased risk of breast cancer (HR = 1.17, 95%CI 1.11, 1.24). Finally, in the stratified analysis, joint effects on the risk of breast cancer were observed between the AL and selected known breast cancer risk factors, including age, family history of breast cancer, PRS, income, physical activity, and alcohol consumption. CONCLUSION: In summary, those findings have demonstrated that higher AL was associated with an increased breast cancer risk in women. This association is likely independent of known breast cancer risk factors. Thus, the AL could be a valuable biomarker to help breast cancer risk prediction and stratification.

Physical Activity During Breast Cancer Therapy Associates With Preserved Exercise Capacity and Cardiac Function (WF97415).

Background: Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. Objectives: This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Methods: Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. Results: BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (ß ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. Conclusions: PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).

An epigenome-wide association study of child appetitive traits and DNA methylation.

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.