Effects of omega-3 fatty acid supplementation on whole blood fatty acid levels

This study was approved by the University of Bridgeport’s Institutional Review Board ID# 2017-11-01, and made possible through a University of Bridgeport Seed Money Grant awarded to Cheryl L. Lyon, N.D.Omega-3 polyunsaturated fatty acids (n-3 PUFA) are popular dietary supplements that have purported beneficial effects for cardiovascular health, inflammatory, autoimmune, and mood disorders. The manufacture of dietary supplements in the United States is not well regulated and concerns surrounding the content and purity of commercially available n-3 PUFA supplements is warranted, as false content labeling and harmful or oxidized fatty acid contaminants may lead to negative health outcomes. In this research, which was part of a larger study assessing the role of nutritional and genetic factors in a sample of chronic musculoskeletal (MSK) pain sufferers, we report differences in whole blood fatty acid levels in a population seeking complementary and integrative health (CIH) care at an urban university-affiliated clinic

Characteristics of chronic musculoskeletal pain sufferers treated in a university-affiliated complementary and integrative health care clinic

This study was approved by the University of Bridgeport’s Institutional Review Board ID# 2017-11-01, and made possible through a University of Bridgeport Seed Money Grant awarded to Cheryl L. Lyon, N.D.Chronic pain is a substantial driver of high health care costs and disability, and disparities in the experience and treatment of pain based on age, sex and race are significant. Patients seeking complementary and integrative health (CIH) approaches for chronic pain are dramatically under-studied, therefore we assessed the role of nutritional, genetic and other factors in a sample of chronic musculoskeletal (MSK) pain sufferers from a unique patient population seeking complementary and integrative health (CIH) care at an urban university-affiliated clinic

Tetrachloroethylene (PCE, Perc) Levels in Residential Dry Cleaner Buildings in Diverse Communities in New York City

Fugitive tetrachloroethylene (PCE, perc) emissions from dry cleaners operating in apartment buildings can contaminate residential indoor air. In 1997, New York State and New York City adopted regulations to reduce and contain perc emissions from dry cleaners located in residential and other buildings. As part of a New York State Department of Health (NYSDOH) study, indoor air perc levels were determined in 65 apartments located in 24 buildings in New York City where dry cleaners used perc on site. Sampling occurred during 2001–2003, and sampled buildings were dispersed across minority and nonminority as well as low-income and higher income neighborhoods. For the entire study area, the mean apartment perc level was 34 μg/m(3), 10-fold lower than mean apartment levels of 340–360 μg/m(3) documented before 1997. The maximum detected perc level was 5,000 μg/m(3), 5-fold lower than the maximum of 25,000 μg/m(3) documented before 1997. Despite these accomplishments, perc levels in 17 sampled apartments still exceeded the NYSDOH residential air guideline of 100 μg/m(3), and perc levels in 4 sampled apartments exceeded 1,000 μg/m(3). Moreover, mean indoor air perc levels in minority neighborhoods (75 μg/m(3)) were four times higher than in nonminority households (19 μg/m(3)) and were > 10 times higher in low-income neighborhoods (256 μg/m(3)) than in higher income neighborhoods (23 μg/m(3)). Logistic regression suitable for clustered data (apartments within buildings) indicated that perc levels on floors 1–4 were significantly more likely to exceed 100 μg/m(3) in buildings located in minority neighborhoods (odds ratio = 6.7; 95% confidence interval, 1.5–30.5) than in nonminority neighborhoods. Factors that may be contributing to the elevated perc levels detected, especially in minority and low-income neighborhoods, are being explored

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

p16(INK4a) Prevents Centrosome Dysfunction and Genomic Instability in Primary Cells

Aneuploidy, frequently observed in premalignant lesions, disrupts gene dosage and contributes to neoplastic progression. Theodor Boveri hypothesized nearly 100 years ago that aneuploidy was due to an increase in centrosome number (multipolar mitoses) and the resultant abnormal segregation of chromosomes. We performed immunocytochemistry, quantitative immunofluorescence, karyotypic analysis, and time-lapse microscopy on primary human diploid epithelial cells and fibroblasts to better understand the mechanism involved in the production of supernumerary centrosomes (more than two microtubule nucleating bodies) to directly demonstrate that the presence of supernumerary centrosomes in genomically intact cells generates aneuploid daughter cells. We show that loss of p16(INK4a) generates supernumerary centrosomes through centriole pair splitting. Generation of supernumerary centrosomes in human diploid epithelial cells was shown to nucleate multipolar spindles and directly drive production of aneuploid daughter cells as a result of unequal segregation of the genomic material during mitosis. Finally, we demonstrate that p16(INK4a) cooperates with p21 through regulation of cyclin-dependent kinase activity to prevent centriole pair splitting. Cells with loss of p16(INK4a) activity have been found in vivo in histologically normal mammary tissue from a substantial fraction of healthy, disease-free women. Demonstration of centrosome dysfunction in cells due to loss of p16(INK4a) suggests that, under the appropriate conditions, these cells can become aneuploid. Gain or loss of genomic material (aneuploidy) may provide the necessary proproliferation and antiapoptotic mechanisms needed for the earliest stages of tumorigenesis

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Comment letters to the National Commission on Commission on Fraudulent Financial Reporting, 1987 (Treadway Commission) Vol. 1

https://egrove.olemiss.edu/aicpa_sop/1661/thumbnail.jp

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Primary cilia regulate branching morphogenesis during mammary gland development.

During mammary gland development, an epithelial bud undergoes branching morphogenesis to expand into a continuous tree-like network of branched ducts [1]. The process involves multiple cell types that are coordinated by hormones and growth factors coupled with signaling events including Wnt and Hedgehog [2-5]. Primary cilia play key roles in the development of many organs by coordinating extracellular signaling (of Wnt and Hedgehog) with cellular physiology [6-8]. During mammary development, we find cilia on luminal epithelial, myoepithelial, and stromal cells during early branching morphogenesis when epithelial ducts extend into the fat pad and undergo branching morphogenesis. When branching is complete, cilia disappear from luminal epithelial cells but remain on myoepithelial and stromal cells. Ciliary dysfunction caused by intraflagellar transport defects results in branching defects. These include decreased ductal extension and decreased secondary and tertiary branching, along with reduced lobular-alveolar development during pregnancy and lactation. We find increased canonical Wnt and decreased Hedgehog signaling in the mutant glands, which is consistent with the role of cilia in regulating these pathways [6-11]. In mammary gland and other organs, increased canonical Wnt [12-14] and decreased Hedgehog [15, 16] signaling decrease branching morphogenesis, suggesting that Wnt and Hedgehog signaling connect ciliary dysfunction to branching defects