Hypoxia-mediated repression of pyruvate carboxylase drives immunosuppression.

BACKGROUND: Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression. METHODS: We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistry, flow cytometry, and global gene expression analyzes of tumor tissue were employed to characterize the impact of PC depletion on tumor immunity. RESULTS: PC is essential for metastatic colonization of the lungs. In contrast, depletion of PC in tumor cells promotes primary tumor growth. This effect was only observed in immune competent animals, supporting the hypothesis that repression of PC can suppress anti-tumor immunity. Exploring key differences between the pulmonary and mammary environments, we demonstrate that hypoxia potently downregulated PC. In the absence of PC, tumor cells produce more lactate and undergo less oxidative phosphorylation. Inhibition of lactate metabolism was sufficient to restore T cell populations to PC-depleted mammary tumors. CONCLUSIONS: We present a dimorphic role for PC in primary mammary tumors vs. pulmonary metastases. These findings highlight a key contextual role for PC-directed lactate production as a metabolic nexus connecting hypoxia and antitumor immunity.

Perceptions and experiences with eating disorder treatment in the first year of COVID-19: A longitudinal qualitative analysis.

OBJECTIVE: The COVID-19 pandemic created significant challenges in accessing and receiving treatment for individuals with eating disorders (EDs). The purpose of this study is to explore perceptions of and experiences with ED treatment during the first year of the pandemic among individuals with past and self-reported EDs in the United States. METHODS: Online surveys were administered to adults (N = 510) with a past or current self-reported ED at 13 timepoints between April 2020 and May 2021. Using longitudinal qualitative analysis, 5651 free-text responses were examined to capture experiences with ED treatment and generate inferences of change over time. RESULTS: We categorized results into four sequential, temporal quarters and identified patterns that explained participants' perceptions of facilitators, barriers, and experiences with ED treatment over time: Quarter 1. Treatment Disruption and Reorienting Recovery; Quarter 2. Accumulating COVID-19 Stress and Virtual Treatment Woes; Quarter 3. A Continuation of Inadequate Care; and Quarter 4. Ongoing Adaptation and Adjustment to Uncertainty. Participant experiences were marked by numerous barriers to accessing care, challenges adjusting to virtual treatment, unmet treatment needs, and beginning acceptance of telehealth. DISCUSSION: Our findings present a timeline to help evaluate challenges related to navigating the switch to virtual care which created significant disruption to ED recovery. Participants spent much of the first year trying to adjust to unemployment, loss of insurance, and lack of access to in-person treatment. Future research should identify additional strategies to improve the receipt and experience of care for EDs. PUBLIC SIGNIFICANCE: Our findings suggest that individuals with eating disorders were significantly challenged by accumulating COVID-19 stress, worsening symptomatology, and limited access to effective treatment during the first year of the pandemic. This knowledge can guide clinicians, treatment centers, and policy makers in addressing the behavioral health needs of individuals impacted by disordered eating amidst emergent public health crises.

The impact of COVID-19 on Black women who binge-eat: a qualitative study.

BACKGROUND: Although studies have traced the impact of COVID-19 on those with eating disorders, little is known about the specific impact of the pandemic on Black American women who report disordered eating behaviors and are at risk for eating disorders. Thus, the purpose of this study is to investigate the impact of COVID-19 on Black women who binge-eat. METHODS: We recruited a purposive sample during the first wave of COVID-19 from the southeastern United States. Participants identified as Black women, reported binge-eating episodes in the last 28 days, and agreed to participate in a semi-structured interview. Prior to the interview, participants were administered a socio-demographic survey and the Eating Disorder Examination-Questionnaire. Interviews were transcribed verbatim and analyzed independently using qualitative content analysis and open coding to identify relevant codes and themes. RESULTS: On average, participants (N = 20) were 43.05 ± 16.2 years of age and reported 5.6 ± 5.7 binge-eating episodes in the last 28 days. We identified six themes to describe participants' experiences managing their eating behavior during COVID-19: (1) food as a coping strategy; (2) lack of control around food; (3) increased time in a triggering environment (e.g., being at home with an easy availability of food); (4) lack of structure and routine; (5) challenges with limited food availability; and (6) positive impact of the pandemic. CONCLUSION: In this study, Black women reported challenges managing their eating behavior during COVID-19. Results could inform the development and tailoring of treatments for Black women reporting disordered eating behaviors. LEVEL OF EVIDENCE: Level V, qualitative interviews.

Creating an appetite awareness and lifestyle modification intervention for Black women at risk for binge eating disorder: A pilot open trial.

Despite the availability of evidence-based interventions to improve binge eating, Black women have some of the lowest rates of access to care for eating disorders. Innovation is needed to offer accessible and culturally relevant treatment options. To this end, using an open trial design, we investigated the feasibility and acceptability of a group-based, appetite awareness training (AAT) + lifestyle modification (LM) programme in Black women at risk for BED in a primary care setting. Participants (n = 20) were Black women recruited from a family medicine centre affiliated with a local public university, and who reported at least two binge eating episodes in the last 28 days. Participants completed a 16-session AAT + LM programme over 4 months. Key outcomes were objective binge eating (assessed by the EDE and the EDE-Q), body dissatisfaction, and weight change, all assessed at baseline, four (post-treatment) and 6 months (2-month follow-up). Ninety-five percent of participants completed assessments at post-treatment and attended nearly 60% of intervention sessions. Among completers (n = 19), body dissatisfaction and objective binge eating decreased from baseline to post-treatment and this decrease was maintained at the 2-month follow-up. In exit interviews, participants reported programme satisfaction. Providing training in appetite awareness combined with lifestyle modification principles may be useful in the treatment of body dissatisfaction and binge eating among Black women.

Effects of Acute Exercise on Anxiety Ratings in Patients With Coronary Heart Disease and Elevated Anxiety.

PURPOSE: To explore individual differences in state anxiety following a single, acute bout of aerobic exercise among anxious patients with diagnosed coronary heart disease (CHD). METHODS: One hundred eighteen CHD patients with elevated symptoms of anxiety enrolled in the UNderstanding the Benefits of Exercise and Escitalopram in Anxious Patients WIth coroNary Heart Disease (UNWIND) clinical trial rated their level of anxiety using a 100-mm visual analog scale before and after a symptom-limited exercise treadmill test. A number of exercise (eg, peak oxygen uptake, exercise duration, maximum heart rate, anaerobic threshold) and psychological variables were examined as potential predictors of exercise response. Changes in anxiety and their association with psychological variables were examined using general linear models. RESULTS: Fifty patients (42%) rated a reduction in anxiety relative to their pre-exercise ratings following the exercise treadmill test. While a number of factors were examined, the only factor that distinguished those individuals who reported a reduction in anxiety symptoms compared with those who either remained the same or actually reported an increase in anxiety was a higher pre-exercise visual analog scale anxiety rating. No differences were observed as a function of sex, severity of trait anxiety, the presence of an anxiety disorder, exercise test duration, or age. CONCLUSIONS: Although many variables were examined, only higher baseline anxiety distinguished those who showed a reduction in their visual analog scale ratings from those whose anxiety remained the same or got worse. The extent to which the response to acute exercise predicts the anxiolytic effects of chronic exercise needs further study.