Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment

Background: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. Results: We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. Conclusions: This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers

Social Norms and Risk Perception: Predictors of Distracted Driving Behavior Among Novice Adolescent Drivers

AbstractPurposeAdolescent drivers are at elevated crash risk due to distracted driving behavior (DDB). Understanding parental and peer influences on adolescent DDB may aid future efforts to decrease crash risk. We examined the influence of risk perception, sensation seeking, as well as descriptive and injunctive social norms on adolescent DDB using the theory of normative social behavior.Methods403 adolescents (aged 16–18 years) and their parents were surveyed by telephone. Survey instruments measured self-reported sociodemographics, DDB, sensation seeking, risk perception, descriptive norms (perceived parent DDB, parent self-reported DDB, and perceived peer DDB), and injunctive norms (parent approval of DDB and peer approval of DDB). Hierarchical multiple linear regression was used to predict the influence of descriptive and injunctive social norms, risk perception, and sensation seeking on adolescent DDB.Results92% of adolescents reported regularly engaging in DDB. Adolescents perceived that their parents and peers participated in DDB more frequently than themselves. Adolescent risk perception, parent DDB, perceived parent DDB, and perceived peer DDB were predictive of adolescent DDB in the regression model, but parent approval and peer approval of DDB were not predictive. Risk perception and parental DDB were stronger predictors among males, whereas perceived parental DDB was stronger for female adolescents.ConclusionsAdolescent risk perception and descriptive norms are important predictors of adolescent distracted driving. More study is needed to understand the role of injunctive normative influences on adolescent DDB. Effective public health interventions should address parental role modeling, parental monitoring of adolescent driving, and social marketing techniques that correct misconceptions of norms related to around driver distraction and crash risk

A scoping review of research on complementary and alternative medicine (CAM) and the mass media: Looking back, moving forward

<p>Abstract</p> <p>Background</p> <p>The use of complementary and alternative medicine (CAM) has become more common in Western developed countries in recent years, as has media reporting on CAM and related issues. Correspondingly, media reports are a primary information source regarding decisions to use CAM. Research on CAM related media reports is becoming increasingly relevant and important; however, identifying key concepts to guide future research is problematic due to the dispersed nature of completed research in this field. A scoping review was conducted to: 1) determine the amount, focus and nature of research on CAM and the mass media; and 2) summarize and disseminate related research results.</p> <p>Methods</p> <p>The main phases were: 1) searching for relevant studies; 2) selecting studies based on pre-defined inclusion criteria; 3) extracting data; and 4) collating, summarizing and reporting the results.</p> <p>Results</p> <p>Of 4,454 studies identified through various search strategies, 16 were relevant to our objectives and included in a final sample. CAM and media research has focused primarily on print media coverage of a range of CAM therapies, although only a few studies articulated differences within the range of therapies surveyed. Research has been developed through a variety of disciplinary perspectives, with a focus on representation research. The research reviewed suggests that journalists draw on a range of sources to prepare media reports, although most commonly they cite conventional (versus CAM) sources and personal anecdotes. The tone of media reports appears generally positive, which may be related to a lack of reporting on issues related to risk and safety. Finally, a variety of discourses within media representations of CAM are apparent that each appeal to a specific audience through resonance with their specific concerns.</p> <p>Conclusion</p> <p>Research on CAM and the mass media spans multiple disciplines and strategies of inquiry; however, despite the diversity in approach, it is clear that issues related to production and reception of media content are in need of research attention. To address the varied issues in a comprehensive manner, future research needs to be collaborative, involving researchers across disciplines, journalists and CAM users.</p

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.]

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts