Placebo in sports nutrition: a proof-of-principle study involving caffeine supplementation

We investigated the effects of supplement identification on exercise performance with caffeine supplementation. Forty-two trained cyclists (age 37 ± 8 years, body mass [BM] 74.3 ± 8.4 kg, height 1.76 ± 0.06 m, maximum oxygen uptake 50.0 ± 6.8 mL/kg/min) performed a ~30 min cycling time-trial 1 h following either 6 mg/kgBM caffeine (CAF) or placebo (PLA) supplementation and one control (CON) session without supplementation. Participants identified which supplement they believed they had ingested (“caffeine”, “placebo”, “don't know”) pre- and post-exercise. Subsequently, participants were allocated to subgroups for analysis according to their identifications. Overall and subgroup analyses were performed using mixed-model and magnitude-based inference analyses. Caffeine improved performance vs PLA and CON (P ≤ 0.001). Correct pre- and post-exercise identification of caffeine in CAF improved exercise performance (+4.8 and +6.5%) vs CON, with slightly greater relative increases than the overall effect of caffeine (+4.1%). Performance was not different between PLA and CON within subgroups (all P > 0.05), although there was a tendency toward improved performance when participants believed they had ingested caffeine post-exercise (P = 0.06; 87% likely beneficial). Participants who correctly identified placebo in PLA showed possible harmful effects on performance compared to CON. Supplement identification appeared to influence exercise outcome and may be a source of bias in sports nutrition

Metastatic breast cancer survival improvement restricted by regional disparity: Surveillance, Epidemiology, and End Results and institutional analysis: 1990 to 2011.

BACKGROUND: The extent of breast cancer outcome disparity can be measured by comparing Surveillance, Epidemiology, and End Results (SEER) breast cancer-specific survival (BCSS) by region and with institutional cohort (IC) rates. METHODS: Patients who were diagnosed with a first primary, de novo, stage IV breast cancer at ages 25 to 84 years from 1990 to 2011 were studied. The change in 5-year BCSS over time from 1990 to 2011 was compared using the SEER 9 registries (SEER 9) without the Seattle-Puget Sound (S-PS) region (n = 12,121), the S-PS region alone (n = 1931), and the S-PS region IC (n = 261). The IC BCSS endpoint was breast cancer death confirmed from chart and/or death certificate and cause-specific survival for SEER registries. BCSS was estimated using the Kaplan-Meier method. Hazard ratios (HzR) were calculated using Cox proportional-hazards models. RESULTS: For SEER 9 without the S-PS region, 5-year BCSS improved 7% (from 19% to 26%) over time, it improved 14% for the S-PS region (21% to 35%), and it improved 27% for the S-PS IC (29% to 56%). In the IC Cox proportional-hazards model, recent diagnosis year, chemotherapy, surgery, and age9, additional significant factors were white race and positive hormone receptor status and S-PS region was associated with better survival (HzR, 0.87; 95% CI, 0.84-0.90). In an adjusted model, hazard of BC death decreased in the most recent time period (2005-2011) by 28% in SEER 9 without S-PS, 43% in the S-PS region and 45% in the IC (HzR, 0.72 [95% CI, 0.67-0.76], 0.57 [95% CI, 0.49-0.66], and 0.55 [95% CI, 0.39-0.78], respectively). CONCLUSIONS: Over 2 decades, the survival of patients with metastatic breast cancer improved nationally, but with regional survival disparity and differential improvement. To achieve equitable outcomes, access and treatment approaches will need to be identified and adopted

Dbl2 Regulates Rad51 and DNA Joint Molecule Metabolism to Ensure Proper Meiotic Chromosome Segregation

To identify new proteins required for faithful meiotic chromosome segregation, we screened a Schizosaccharomyces pombe deletion mutant library and found that deletion of the dbl2 gene led to missegregation of chromosomes during meiosis. Analyses of both live and fixed cells showed that dbl2Δ mutant cells frequently failed to segregate homologous chromosomes to opposite poles during meiosis I. Removing Rec12 (Spo11 homolog) to eliminate meiotic DNA double-strand breaks (DSBs) suppressed the segregation defect in dbl2Δ cells, indicating that Dbl2 acts after the initiation of meiotic recombination. Analyses of DSBs and Holliday junctions revealed no significant defect in their formation or processing in dbl2Δ mutant cells, although some Rec12-dependent DNA joint molecules persisted late in meiosis. Failure to segregate chromosomes in the absence of Dbl2 correlated with persistent Rad51 foci, and deletion of rad51 or genes encoding Rad51 mediators also suppressed the segregation defect of dbl2Δ. Formation of foci of Fbh1, an F-box helicase that efficiently dismantles Rad51-DNA filaments, was impaired in dbl2Δ cells. Our results suggest that Dbl2 is a novel regulator of Fbh1 and thereby Rad51-dependent DSB repair required for proper meiotic chromosome segregation and viable sex cell formation. The wide conservation of these proteins suggests that our results apply to many species

PRAK Is Essential for ras-Induced Senescence and Tumor Suppression

Like apoptosis, oncogene-induced senescence is a barrier to tumor development. However, relatively little is known about the signaling pathways mediating the senescence response. p38regulated/activated protein kinase (PRAK) is a p38 MAIPIK substrate whose physiological functions are poorly understood. Here we describe a role for PRAK in tumor suppression by demonstrating that PRAK mediates senescence upon activation by p38 in response to oncogenic ras. PRAK deficiency in mice enhances DMBA-induced skin carcinogenesis, coinciding with compromised senescence induction. In primary cells, inactivation of PRAK prevents senescence and promotes oncogenic transformation. Furthermore, we show that PRAK activates p53 by direct phosphorylation. We propose that phosphorylation of p53 by PRAK following activation of p38 MAPK by ras plays an important role in ras-induced senescence and tumor suppression