BACKGROUND: The circadian system entrains behavioral and physiological rhythms to environmental cycles, and modern lifestyles disrupt this entrainment. We investigated a timed exercise intervention to phase shift the internal circadian rhythm. METHODS: In 52 young, sedentary adults, dim light melatonin onset (DLMO) was measured before and after 5 days of morning (10 hours after DLMO; n = 26) or evening (20 hours after DLMO; n = 26) exercise. Phase shifts were calculated as the difference in DLMO before and after exercise. RESULTS: Morning exercise induced phase advance shifts (0.62 ± 0.18 hours) that were significantly greater than phase shifts from evening exercise (–0.02 ± 0.18 hours; P = 0.01). Chronotype also influenced the effect of timed exercise. For later chronotypes, both morning and evening exercise induced phase advances (0.54 ± 0.29 hours and 0.46 ±0.25 hours, respectively). In contrast, earlier chronotypes had phase advances from morning exercise (0.49 ± 0.25 hours) but had phase delays from evening exercise (–0.41 ± 0.29 hours). CONCLUSION: Late chronotypes — those who experience the most severe circadian misalignment — may benefit from phase advances induced by exercise in the morning or evening, but evening exercise may exacerbate circadian misalignment in early chronotypes. Thus, personalized exercise timing prescription, based on chronotype, could alleviate circadian misalignment in young adults. TRIAL REGISTRATION: Trial registration can be found at www.clinicaltrials.gov (NCT04097886). FUNDING: Funding was supplied by NIH grants UL1TR001998 and TL1TR001997, the Barnstable Brown Diabetes and Obesity Center, the Pediatric Exercise Physiology Laboratory Endowment, the Arvle and Ellen Turner Thacker Research Fund, and the University of Kentucky.

Bystander-based violence prevention interventions have shown efficacy to reduce dating violence and sexual violence acceptance at the individual level yet no large randomized controlled trial (RCT) has evaluated this effect at the high-school level and over time. This rigorous cluster-randomized controlled trial addresses this gap by evaluating intervention effectiveness at both school and individual levels. Kentucky high schools were randomized to intervention or control conditions. In intervention schools educators provided school-wide ‘Green Dot’ presentations and bystander training with student popular opinion leaders. Each spring from 2010 to 2014; 73,044 students completed anonymous surveys with no missing data on relevant outcomes. Dating violence and sexual violence acceptance were the primary outcomes for this analysis. At the school level, slopes from linear mixed models using averaged school-level dating violence acceptance (condition–time, p < 0.001) and sexual violence acceptance (condition–time interaction, p < 0.001) differed indicating a significant reduction in the violence acceptance in the intervention relative to control schools over time and specifically in years 3 and 4 when ‘Green Dot’ was fully implemented. Analyses based on student’s self-reported receipt of ‘Green Dot’ training by condition confirmed the school level finding of significant reductions in both dating violence and sexual violence acceptance in years 3 and 4 for both males and females. In this RCT we find evidence that the bystander-based violence prevention intervention ‘Green Dot’ works, as hypothesized and as implemented, to reduce acceptance of dating violence and sexual violence at the school and individual levels.

Muscle mass and strength are strong determinants of a person’s quality of life and functional independence with advancing age. While resistance training is the most effective intervention to combat age-associated muscle atrophy (sarcopenia), the ability of older adults to increase muscle mass and strength in response to training is blunted and highly variable. Thus, finding novel ways to complement resistance training to improve muscle response and ultimately quality of life among older individuals is critical. The purpose of this study is to determine whether a commonly prescribed medication called metformin can be repurposed to improve the response to resistance exercise training by altering the muscle tissue inflammatory environment. Individuals aged 65 and older are participating in a two-site, randomized, double-blind, placebo-controlled trial testing the effects of metformin or placebo on muscle size, strength, and physical function when combined with a progressive resistance training program. Participants consume 1700 mg of metformin per day or placebo for 2 weeks before engaging in a 14-week progressive resistance training regimen, with continued metformin or placebo. Participants are then monitored post-training to determine if the group taking metformin derived greater overall benefit from training in terms of muscle mass and strength gains than those on placebo. Muscle biopsies are taken from the vastus lateralis at three time points to assess individual cellular and molecular adaptations to resistance training and also changes in response to metformin. The response of aged muscles to a resistance training program does not always result in a positive outcome; some individuals even experience a loss in muscle mass following resistance training. Thus, adjuvant therapies, including pharmacological ones, are required to optimize response to training in those who do not respond and may be at increased risk of frailty. This is the first known metformin repurposing trial in non-diseased individuals, aimed specifically at the resistance exercise “non-responder” phenotype present in the aging population. The overall goal of this trial is to determine if combined exercise-metformin intervention therapy will benefit older individuals by promoting muscle hypertrophy and strength gains, thereby maintaining functional independence. ClinicalTrials.gov, NCT02308228 . Registered on 25 November 2014.

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults >30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. Moderate/severe disease patients had lower cis-β-carotene levels across all racial/ethnic groups and these decreased levels in moderate/severe periodontitis were exacerbated with age. β-cryptoxanthin demonstrated lower levels in severe disease patients across the entire age range in all racial/ethnic groups. Folate differences were evident across the various age groups with consistently lower levels in periodontitis patients >30 years and most pronounced in females. Lower levels of vitamin D were consistently noted across the entire age range of patients with a greater difference seen in females with periodontitis. Finally, an analytical approach to identify interactions among these nutrients related to age and periodontitis showed interactions of vitamin D in females, and folate with race in the population. These findings suggest that improving specific nutrient intake leading to elevated blood levels of a combination of these protective factors may provide a novel strategy to affect the significant increase in periodontitis that occurs with aging.

This study extends prior analyses from a 5-year multisite cluster-randomized controlled trial to examine how the previously reported effects of the Green Dot bystander-based prevention program worked to reduce violence perpetration. Bystander-based interventions are hypothesized to prevent violence by reducing violence acceptance and increasing trained participants’ willingness and ability to actively engage others in violence prevention using safe and effective bystander actions to diffuse or avoid potentially violent situations. We tested this hypothesis by examining whether Green Dot worked to reduce violence through two mediators measured over time: reducing violence acceptance and increasing bystander actions. When accounting for changes in these mediators over time, the effect of this intervention on violence perpetration was hypothesized to be attenuated or explained. At baseline (spring 2010) and annually (2011-2014), all students in recruited high schools (13 intervention, 13 control) completed an anonymous survey (response rate = 83.9%). Student responses were aggregated as school-level counts for the analysis. Path analyses estimated direct and indirect effects at specific points in the implementation of the intervention. Longitudinal models were used to determine if changes in violence acceptance and bystander actions could explain or attenuate the effect of the intervention. Time-framed path model analyses indicated that the intervention worked as expected to increase bystander behaviors and reduce violence acceptance; both potential mediators were significantly associated with sexual violence perpetration. In addition, after adjusting intent-to-treat models for the hypothesized mediators, the intervention was no longer associated with violence perpetration. In conclusion, these findings indicate that this bystander intervention worked as hypothesized to reduce sexual violence perpetration by creating theory-based changes in students’ violence acceptance and bystander actions.