INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population.</p> <p>Methods/design</p> <p>The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m²) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 μg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study.</p> <p>Discussion</p> <p>The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available.</p> <p>Study number</p> <p>EMR 63325-012</p> <p>Trial Registration</p> <p>Clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015443">NCT01015443</a></p

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Timescales of Multineuronal Activity Patterns Reflect Temporal Structure of Visual Stimuli

The investigation of distributed coding across multiple neurons in the cortex remains to this date a challenge. Our current understanding of collective encoding of information and the relevant timescales is still limited. Most results are restricted to disparate timescales, focused on either very fast, e.g., spike-synchrony, or slow timescales, e.g., firing rate. Here, we investigated systematically multineuronal activity patterns evolving on different timescales, spanning the whole range from spike-synchrony to mean firing rate. Using multi-electrode recordings from cat visual cortex, we show that cortical responses can be described as trajectories in a high-dimensional pattern space. Patterns evolve on a continuum of coexisting timescales that strongly relate to the temporal properties of stimuli. Timescales consistent with the time constants of neuronal membranes and fast synaptic transmission (5–20 ms) play a particularly salient role in encoding a large amount of stimulus-related information. Thus, to faithfully encode the properties of visual stimuli the brain engages multiple neurons into activity patterns evolving on multiple timescales

SEX DIFFERENCES IN HYDRATION AND ACUTE KIDNEY INJURY BIOMARKERS AT THE 2019 B.A.A. BOSTON MARATHON

Whitley C. Atkins1, Cory L. Butts2, Melani R. Kelly3, Chris Troyanos4, R. Mark Laursen5, Andrew Duckett5, Dawn M. Emerson3, Brendon P. McDermott1, FACSM 1University of Arkansas, Fayetteville, Arkansas; 2Weber State University, Ogden, Utah; 3University of Kansas, Lawrence, Kansas; 4Boston Athletic Association, Boston, Massachusetts; 5Boston University, Boston, Massachusetts There are several studies demonstrating that acute kidney injury (AKI) is common immediately following marathon running. Many studies further suggest complete biomarker recovery within 24-hr. To date, however, sex differences in distance runners have received little investigation. Purpose: To evaluate sex differences on hydration and AKI biomarker changes surrounding running a marathon. Methods: Sixty-three participants (32 males and 31 females) in the Boston Athletic Association’s Boston Marathon (45.9 ± 9 y, 65.4 ± 10.8 kg, finishing time 3.78 ± 0.55 h) provided urine samples at three time points (pre-marathon, post-marathon and 24-hr postmarathon) for this study. Urine specific gravity (USG) was analyzed via refractometry and AKI biomarkers were evaluated using commercially available enzyme-linked immunosorbent assays. A 2 x 3 (sex x time) RM-ANOVA was used for statistical analysis post-hoc comparisons were completed with Bonferroni adjustments due to multiple time point comparisons. Results: Female USG (1.020 ± .001) was significantly greater post-marathon than male USG (1.016 ± .001; p = .028), yet male USG (1.024 ± .002) was significantly elevated 24-hr post-marathon compared to females (1.017 ± .002; p=.008). Female uCr values (186.91 ± 32.08 mg/dL) were significantly greater 24-hr post-marathon than males (59.24 ± 34.76 mg/dL, p ). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) post-marathon was greater for both males (33.94 ± 10.84 ng/mL) and females (48.02 ± 10.00 ng/mL, p≤.001) compared to baseline (males: 4.27 ± 5.75 ng/mL, females: 22.68 ± 5.19 ng/mL). Twenty-four-hr post-marathon uNGAL was greater for both sexes (males: 65.76 ± 5.61 ng/mL, females: 60.16 ± 5.16 ng/mL, p=.004) compared to pre-marathon and post-marathon values but the effect of sex on uNGAL was not significant (p=.300). Conclusions: We identified persistent elevations in AKI biomarkers beyond 24-hr, regardless of sex. Further, this study highlights apparent sex differences in hydration and AKI outcomes of runners completing marathons. The need to further investigate sex differences and potential interactions between marathon running, hydration outcomes, hormone levels and AKI is warranted

Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in mdr1a−/− mice, a model of inflammatory bowel diseases

Objective: Enteric microbiota has been shown to be associated with various pathological conditions such as inflammatory bowel disease (IBD). This study aimed to determine the anti-inflammatory colonic effects of blueberries and broccoli in mdr1a -/- mice (IBD mouse model) through modification of microbiota composition in the gastrointestinal tract. Methods: The mdr1a -/- mice were fed either a control diet or the control diet supplemented with either 10% blueberry or broccoli for 21 wk. We investigated the influence of these diets on cecal microbiota and organic acids, colon morphology, and bacterial translocation to mesenteric lymph nodes. Results: In comparison to mice fed the control diet, blueberry and broccoli supplementation altered cecum microbiota similarly with the exception of Faecalibacterium prausnitzii, which was found to be significantly lower in broccoli-fed mice. High concentrations of butyric acid and low concentrations of succinic acid were observed in the cecum of broccoli-fed mice. Blueberry- and broccoli-supplemented diets increased colon crypt size and the number of goblet cells per crypt. Only the broccoli-supplemented diet significantly lowered colonic inflammation compared to mice fed the control diet. Translocation of total microbes to mesenteric lymph nodes was lower in broccoli-fed mice compared to blueberry and control diet groups. Conclusion: Dietary blueberries and/or broccoli altered the composition and metabolism of the cecal microbiota and colon morphology. Overall, these results warrant further investigation through clinical studies to establish whether the consumption of blueberries and/or broccoli is able to alter the composition and metabolism of large intestine microbiota and promote colon health in humans. © 2012 Elsevier Inc