1,724,441 research outputs found
Program Evaluation, Asylum Evaluation Training
No full textData includes:
Qualitative dataset from attendee responses
Quantitative dataset from attendee responses and RSVPs
Code counts for qualitative dat
Immunomodulation of Inflammatory Response in Osteoarthritis: Therapeutic Potential of Blocking Il-33/ST2 Receptor
No full textOsteoarthritis is a degenerative joint disease of the articular cartilage characterized by the loss of cartilage, limited range of motion, joint pain and tenderness, and limited physical movements. An imbalance between regenerative and degenerative factors results in increased loss of cartilage leading to osteoarthritis. Osteoarthritis is not only a disease of cartilage but involves the whole joint including tendon, ligament, meniscus, muscle, and synovial membrane. The weakness of the quadriceps muscles and inflammation of the articular structures of the joint enhance the progression of cartilage degeneration and loss. The weakness of the muscles may be due to vitamin D deficiency, which in turn is associated with chronic inflammation and an increased prevalence and incidence of osteoarthritis. The initial damage caused by mechanical or shear stress, trauma or injury, or an improper gait results in the secretion of damage associated molecular patterns (DAMPs) including high mobility group box-1 (HMGB-1), receptor for advanced glycation end products (RAGE), and alarmins (S100A8 and S100A9). Aging can also result in physiological accumulation of advanced glycation end products (AGEs). These DAMPs instigate a cascade of inflammatory responses and increase the secretion of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α, and anti-inflammatory cytokines IL-10 and IL-37. Increased secretion of these pro-inflammatory cytokines results in the recruitment of inflammatory cells such as monocytes and macrophages. The activation of various inflammatory and pro-damage mediators including triggering receptor expressed on myeloid cells (TREMs), toll like receptors (TLRs), cytoplasmic kinases, transcriptional factors, and matrix metalloproteinases (MMPs). The role of these pro-inflammatory cytokines and inflammatory and pro-damage mediators in the pathogenesis of rheumatoid arthritis, synovitis, and osteoarthritis has been well described. The role of newly discovered cytokines of IL-1 family, IL-33 and IL-37, in the pathogenesis of rheumatoid arthritis and synovitis has been reported in the literature. However, their role in relation to osteoarthritis is yet to be established. Increased secretion of DAMPs is associated with an increased production of pro-inflammatory cytokine IL-33, whereas the increase in inflammation results in the secretion of anti-inflammatory cytokine IL-37 as a compensatory mechanism. Since vitamin D deficiency is associated with chronic inflammation and osteoarthritis, and vitamin D regulates the secretion of IL-33 and IL-37; one may speculate that vitamin D could also play a crucial role in the pathogenesis of osteoarthritis and may affect IL-33 and IL-37 effects on mediators of inflammation within the joint. IL-33, IL-37, and vitamin D play a crucial role in macrophage differentiation and polarization, the main effectors of chronic inflammation within the joint. Taken together, it is logical to infer that IL-33, IL-37, and vitamin D interactions may have an immunomodulatory effect on the expression levels and action of various pro-inflammatory and pro-damage mediators. However, the immunomodulatory role of IL-33, IL-37, and vitamin D in OA has not been reported in the literature. In this study, for the first time, the interactive and counteractive role of IL-33, IL-37, and vitamin D on TREM-1, TREM-2, TLR-2, TLR-4, NF-κB, RAGE, HMGB-1, MMP-2, MMP-9, and macrophage polarization has been elucidated using normal and osteoarthritic human chondrocytes and the expression levels of these have been analyzed in osteoarthritic human knee and hip cartilage, and vitamin D deficient, vitamin D sufficient, and vitamin D supplemented hyperlipidemic microswine.ProQuest Traditional Publishing Optio
Vitamin D A Negative Regulator of Triggering Receptor Expressed on Myeloid Cell-1 (TREM-1) in Hepatocellular Carcinoma Cells
No full textHepatocellular carcinoma (HCC) accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Exposure to toxic substance and exposure to infectious agents like HBV (hepatitis B virus) and HCV (hepatitis C virus) are the main risk factors for development of HCC. Chronic inflammation precedes the development of cirrhosis and HCC. TREM-1(triggering receptor expressed on myeloid cell-1) is an inflammatory marker and amplifier of inflammation. HMGB-1 secreted from necrotizing cells activates TREM-1 at cell surface. It further signals through PI3K and ERK1/2 to activate NF-κB transcription factor resulting in the production of pro-inflammatory cytokines namely IL-6 and TNF-α. These pro-inflammatory cytokines further enhance the inflammation to change the microenvironment and predisposing the liver to carcinogenesis. Low levels of vitamin D have been associated with liver diseases such as alcoholic liver disease, non-alcoholic steatohepatitis, and HBV and HCV infection. Low level of vitamin D is a poor prognostic factor and supplementation of vitamin D with antiviral therapy in HCV has proven beneficial. Vitamin D is an anti-inflammatory agent and acts through vitamin D receptor in the cells to suppress inflammation in various diseases. Vitamin D also decreases proliferation in various tumors and hence it can be used to decrease chronic inflammation in liver diseases. I found significantly increased expression of TREM-1, HMGB-1 and DAP-12 in HepG-2 cells (hepatocellular carcinoma cell line) compared to THLE-2 (epithelial cells transformed with Sv40 large T antigen) cells. Pro-inflammatory cytokines, IL-6 and TNF-α further significantly increased the TREM-1 expression in HepG-2 and THLE-2 cells. Treatment of HepG-2 cells with calcitriol attenuated the TREM-1 expression as well as the stimulatory effect of pro-inflammatory cytokines IL-6 and TNF-α on TREM-1 expression. Further, calcitriol also decreased the proliferation, invasion and migration of HepG-2 cells, suggesting that vitamin D supplementation can be used to attenuate the ongoing chronic inflammation in hepatitis and cirrhosis, and the progression to hepatocellular carcinoma can be delayed. This study provides molecular and biochemical evidence that suppression of TREM-1 by vitamin D supplementation together with conventional treatment of hepatitis, fibrosis and chronic hepatitis may be a novel strategy and promising target for delaying the progression of liver disease and hepatocellular carcinoma.ProQuest Traditional Publishing Optio
Securitization and mortgage default
Get PDFThe academic literature, the popular press, and policymakers have all debated securitization's contribution to the poor performance of mortgages originated in the run-up to the recent crisis. Theoretical arguments have been advanced on both sides, but the lack of suitable data has made it difficult to assess them empirically. The author examines this issue by using a loan-level data set from LPS Analytics, covering approximately two-thirds of the mortgages originated in 2005 and 2006, and including both securitized and nonsecuritized loans. ; The author finds evidence that privately securitized loans do indeed perform worse than observably similar, nonsecuritized loans. Moreover, this effect is strongest in prime mortgage markets, which have not been studied in the previous literature. For example, a typical prime loan becomes delinquent at a 20 percent higher rate if it is privately securitized, ceteris paribus. This is consistent with the existence of adverse selection; that is, that lenders used information not available to investors to securitize loans that were riskier than they otherwise appeared. By contrast, for subprime mortgages, the impact of private securitization is concentrated in low or no-documentation loans; this latter result is consistent with previous work such as Keys et al. (2009).Mortgage-backed securities ; Default (Finance)
sj-docx-4-pie-10.1177_09544089221087821 - Supplemental material for Design and development of a rapid prototyping system combining traditional fused deposition modeling and reconfigurable pins platform
No full textSupplemental material, sj-docx-4-pie-10.1177_09544089221087821 for Design and development of a rapid prototyping system combining traditional fused deposition modeling and reconfigurable pins platform by Vikrant Charak and Amit Kumar Sinha in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering</p
sj-docx-2-pie-10.1177_09544089221087821 - Supplemental material for Design and development of a rapid prototyping system combining traditional fused deposition modeling and reconfigurable pins platform
No full textSupplemental material, sj-docx-2-pie-10.1177_09544089221087821 for Design and development of a rapid prototyping system combining traditional fused deposition modeling and reconfigurable pins platform by Vikrant Charak and Amit Kumar Sinha in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering</p
sj-docx-3-pie-10.1177_09544089221087821 - Supplemental material for Design and development of a rapid prototyping system combining traditional fused deposition modeling and reconfigurable pins platform
No full textSupplemental material, sj-docx-3-pie-10.1177_09544089221087821 for Design and development of a rapid prototyping system combining traditional fused deposition modeling and reconfigurable pins platform by Vikrant Charak and Amit Kumar Sinha in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering</p
Role of Risk Stratification and Genetics in Sudden Cardiac Death
Get PDFSudden cardiac death (SCD) is a major public health issue due to its increasing incidence in the general population and the difficulty in identifying high-risk individuals. Nearly 300,000-350,000 patients in the United States and 4- to 5 million patients in the world die from SCD. Coronary artery disease and advanced heart failure are the main etiology for SCD. Ischemia of any cause precipitates lethal arrhythmias, and ventricular tachycardia and ventricular fibrillation are the most common lethal arrhythmias precipitating SCD. Pulse-less electrical activity, brady-arrhythmia and electromechanical dissociation also result in SCD. Most sudden cardiac deaths occur out-of-the-hospital setting, so it is difficult to estimate the public burden, which results in overestimating the incidence of SCD. The insufficiency and limited predictive value of various indicators and criteria for SCD result in the increasing incidences. As a result, there is a need to develop better risk stratification criteria and find modifiable variables to decrease the incidence. Primary and secondary prevention and treatment of SCD need further research. This critical review is focused on the etiology, risk factors, prognostic factors and importance of risk stratification of SCD.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
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