BACKGROUND: Studies have established the central role of the family in the recognition, treatment, and recovery of anorexia nervosa. The objective of this study was to review, synthesize, and critically appraise the literature on parents views on the treatment and recovery process of anorexia nervosa in their adolescent child. METHOD: A systematic search of Medline, PsychINFO, CINHAL, EMBASE, Cochrane library, and SSCI was conducted for qualitative studies published regarding parents views about the treatment of anorexia nervosa. The quality of articles was assessed using the critical appraisal skills program (CASP) and findings were analysed using thematic synthesis. RESULTS: A total of 25 studies from nine countries reporting the views of 357 parents met the inclusion criteria. Four major themes were developed from the analysis: understanding the child and the disease, experience of services and treatment modalities, the role of professionals, and the experience of recovery. CONCLUSION: Parents report struggles with delays in finding help, judgmental attitudes of professionals, and uncertainty about the future. Recognition of the challenges faced by parents and families empowers clinicians to build stronger therapeutic relationships essential for long-term recovery from anorexia nervosa.

BACKGROUND: Previous literature has explored the relationship between television viewing and cardiovascular disease (CVD) in adults; however, there remains a paucity of longitudinal data describing how young adult television viewing relates to premature CVD events. OBJECTIVE: To ascertain the relationship between level and annualized changes in television viewing from young adulthood to middle age and the incidence of premature CVD events before age 60. DESIGN: The Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort with over 30 years of follow-up (1985-present). PARTICIPANTS: Black and White men and women who were 18-30 years old at baseline (1985-1986). MAIN MEASURES: Independent variables: Individualized television viewing trajectories were developed using linear mixed models. DEPENDENT VARIABLES: Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome. KEY RESULTS: Among 4318 included participants, every 1-h increase in daily hours of television viewing at age 23 was associated with higher odds of incident CHD (adjusted odds ratio [AOR] 1.26, 95% confidence interval [CI] 1.06-1.49) and incident CVD events (AOR 1.16, 95% CI 1.03-1.32). Each additional hour of daily television viewing annually was associated with higher annual odds of CHD incidence (AOR 1.55, 95% CI 1.06-2.25), stroke incidence (AOR 1.58, 95% CI 1.02-2.46), and CVD incidence (AOR 1.32, 95% CI 1.03-1.69). Race and sex modified the association between television viewing level at age 23 and CHD, heart failure, and stroke, with White men most consistently having significant associations. CONCLUSIONS: In this prospective cohort study, greater television viewing in young adulthood and annual increases in television viewing across midlife were associated with incident premature CVD events, particularly CHD. Young adulthood as well as behaviors across midlife may be important periods to promote healthy television viewing behavior patterns.

Purpose

Prostate-specific membrane antigen (PSMA) targeting radioligands deliver radiation to PSMA-expressing cells. However, the relationship between PSMA levels and intralesion heterogeneity of PSMA expression, and cytotoxic radiation by radioligand therapy (RLT) is unknown. Here we investigate RLT efficacy as function of PSMA levels/cell, and the fraction of PSMA⁺ cells in a tumor.

Experimental design

RM1 cells expressing different levels of PSMA (PSMA^-, PSMA⁺, PSMA⁺⁺, PSMA⁺⁺⁺; study 1) or a mix of PSMA⁺ and PSMA^- RM1 (study 2, 4) or PC-3/PC-3-PIP (study 3) cells at various ratios were injected into mice. Mice received ¹⁷⁷Lu- (studies 1-3) or ²²⁵Ac- (study 4) PSMA617. Tumor growth was monitored. Two days post-RLT, tumors were resected in a subset of mice. Radioligand uptake and DNA damage were quantified.

Results

¹⁷⁷Lu-PSMA617 efficacy increased with increasing PSMA levels (study 1) and fractions of PSMA positive cells (studies 2, 3) in both, the RM1 and PC-3-PIP models. In tumors resected 2 days post-RLT, PSMA expression correlated with ¹⁷⁷Lu-PSMA617 uptake and the degree of DNA damage. Compared with ¹⁷⁷Lu-PSMA617, ²²⁵Ac-PSMA617 improved overall antitumor effectiveness and tended to enhance the differences in therapeutic efficacy between experimental groups.

Conclusions

In the current models, both the degree of PSMA expression and the fraction of PSMA⁺ cells correlate with ¹⁷⁷Lu-/²²⁵Ac-PSMA617 tumor uptake and DNA damage, and thus, RLT efficacy. Low or heterogeneous PSMA expression represents a resistance mechanism to RLT.See related commentary by Ravi Kumar and Hofman, p. 2774.

Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the disease in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.Leukemic cells depend on the nucleotide synthesis pathway to proliferate. Here the authors use metabolomics and proteomics to show that inhibition of ATR reduced the activity of these pathways thus providing a valuable therapeutic target in leukemia.