Coordinated Induction of Antimicrobial Response Factors in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated autoantibody production and complement activation leading to multi-organ damage. The disease is associated with increased intestinal permeability. In this study, we tested the hypothesis that SLE subjects have increased systemic exposure to bacteria. Since bacteria induce the expression of antimicrobial response factors (ARFs), we measured the levels of a series of clinically relevant ARFs in the plasma of SLE subjects. We found that levels of sCD14, lysozyme, and CXCL16 were significantly elevated in SLE subjects. A strong positive correlation was also observed between sCD14 and SELENA-SLEDAI score. Interestingly, the ratio of EndoCAb IgM:total IgM was significantly decreased in SLE and this ratio was negatively correlated with sCD14 levels. Although, there were no significant differences in the levels of lipopolysaccharide binding protein (LBP) and fatty acid binding protein 2 (FABP2), we observed significant positive correlations between lysozyme levels and sCD14, LBP, and FABP2. Moreover, galectin-3 levels also positively correlate with lysozyme, sCD14, and LBP. Since our SLE cohort comprised 43.33% males, we were able to identify gender-specific changes in the levels of ARFs. Overall, these changes in the levels and relationships between ARFs link microbial exposure and SLE. Approaches to reduce microbial exposure or to improve barrier function may provide therapeutic strategies for SLE patients

Growth Response of Kenhy Fescue to Nitrogen Fertilizer

Kenhy fescue is a new, improved variety of tall fescue which has recently been released by the University of Kentucky Agricultural Experiment Station and the U.S.D.A. Agricultural Research Service (see University of Kentucky publication AGR-60, Kenhy A New Tall Fescue Variety ). Seed of this variety should become available to farmers in limited quantities in the summer 1977. The purpose of this report is to provide information on how this newly developed fescue variety produces as affected by time and rate of nitrogen application

Coordinated Induction of Antimicrobial Response Factors in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated autoantibody production and complement activation leading to multi-organ damage. The disease is associated with increased intestinal permeability. In this study, we tested the hypothesis that SLE subjects have increased systemic exposure to bacteria. Since bacteria induce the expression of antimicrobial response factors (ARFs), we measured the levels of a series of clinically relevant ARFs in the plasma of SLE subjects. We found that levels of sCD14, lysozyme, and CXCL16 were significantly elevated in SLE subjects. A strong positive correlation was also observed between sCD14 and SELENA-SLEDAI score. Interestingly, the ratio of EndoCAb IgM:total IgM was significantly decreased in SLE and this ratio was negatively correlated with sCD14 levels. Although, there were no significant differences in the levels of lipopolysaccharide binding protein (LBP) and fatty acid binding protein 2 (FABP2), we observed significant positive correlations between lysozyme levels and sCD14, LBP, and FABP2. Moreover, galectin-3 levels also positively correlate with lysozyme, sCD14, and LBP. Since our SLE cohort comprised 43.33% males, we were able to identify gender-specific changes in the levels of ARFs. Overall, these changes in the levels and relationships between ARFs link microbial exposure and SLE. Approaches to reduce microbial exposure or to improve barrier function may provide therapeutic strategies for SLE patients

Long-Term Memory for the Terrorist Attack of September 11: Flashbulb Memories, Event Memories, and the Factors That Influence Their Retention

More than 3,000 individuals from 7 U.S. cities reported on their memories of learning of the terrorist attacks of September 11, as well as details about the attack, 1 week, 11 months, and/or 35 months after the assault. Some studies of flashbulb memories examining long-term retention show slowing in the rate of forgetting after a year, whereas others demonstrate accelerated forgetting. This article indicates that (a) the rate of forgetting for flashbulb memories and event memory (memory for details about the event itself) slows after a year, (b) the strong emotional reactions elicited by flashbulb events are remembered poorly, worse than nonemotional features such as where and from whom one learned of the attack, and (c) the content of flashbulb and event memories stabilizes after a year. The results are discussed in terms of community memory practices.James S. McDonnell FoundationNational Institutes of Health (U.S.) (grant R01- MH0066972

A ten-year follow-up of a study of memory for the attack of September 11, 2001: Flashbulb memories and memories for flashbulb events.

Within a week of the attack of September 11, 2001, a consortium of researchers from across the United States distributed a survey asking about the circumstances in which respondents learned of the attack (their flashbulb memories) and the facts about the attack itself (their event memories). Follow-up surveys were distributed 11, 25, and 119 months after the attack. The study, therefore, examines retention of flashbulb memories and event memories at a substantially longer retention interval than any previous study using a test-retest methodology, allowing for the study of such memories over the long term. There was rapid forgetting of both flashbulb and event memories within the first year, but the forgetting curves leveled off after that, not significantly changing even after a 10-year delay. Despite the initial rapid forgetting, confidence remained high throughout the 10-year period. Five putative factors affecting flashbulb memory consistency and event memory accuracy were examined: (a) attention to media, (b) the amount of discussion, (c) residency, (d) personal loss and/or inconvenience, and (e) emotional intensity. After 10 years, none of these factors predicted flashbulb memory consistency; media attention and ensuing conversation predicted event memory accuracy. Inconsistent flashbulb memories were more likely to be repeated rather than corrected over the 10-year period; inaccurate event memories, however, were more likely to be corrected. The findings suggest that even traumatic memories and those implicated in a community's collective identity may be inconsistent over time and these inconsistencies can persist without the corrective force of external influences.This is the author accepted manuscript. The final version is available from the American Psychological Association via http://dx.doi.org/10.1037/xge000005

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases

The comparative effectiveness of decision aids in diverse populations with early stage prostate cancer: a study protocol for a cluster-randomized controlled trial in the NCI Community Oncology Research Program (NCORP), Alliance A191402CD

Abstract Background Treatments for localized prostate cancer present challenging tradeoffs in the face of uncertain treatment benefits. These options are best weighed in a process of shared decision-making with the patient’s healthcare team. Minority men experience disparities in prostate cancer outcomes, possibly due in part to a lack of optimal communication during treatment selection. Decision aids facilitate shared decision-making, improve knowledge of treatment options, may increase satisfaction with treatment choice, and likely facilitate long-term quality of life. Methods/design This study will compare the effect of two evidence-based decision aids on patient knowledge and on quality of life measured one year after treatment, oversampling minority men. One decision aid will be administered prior to specialist consultation, preparing patients for a treatment discussion. The other decision aid will be administered within the consultation to facilitate transparent, preference-sensitive, and evidence-informed deliberations. The study will utilize a four-arm, block-randomized design to test whether each decision aid alone (Arms 1 and 2) or in combination (Arm 3) can improve patient knowledge and quality of life compared to usual care (Arm 4). The study, funded by the National Cancer Institute’s Community Oncology Research Program (NCORP), will be deployed within select institutions that have demonstrated capacity to recruit minority populations into urologic oncology trials. Discussion Upon completion of the trial, we will have 1) tested the effectiveness of two evidence-based decision aids in enhancing patients’ knowledge of options for prostate cancer therapy and 2) estimated whether decision aids may improve patient quality of life one year after initial treatment choice. Trial registration Clinicaltrials.gov: NCT03103321 . The trial registration date (on ClinicalTrials.gov) was April 6, 2017