There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

http://science.sciencemag.org/content/sci/284/5411/143.full.pdf

Multilineage Potential of Adult Human Mesenchymal Stem Cells

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

This invention relates to compositions (e.g. vaccine compositions) which can be used to provide a subject with protective immunity against a parasite infection. The compositions comprise: (i) an immunologically effective amount of a nucleic acid (e.g. a nucleic acid-based vaccine) comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen; (ii) a parasite MIF antigen; or (iii) an antibody which specifically binds to a parasite MIF antigen. The compositions may be used to treat infections and diseases caused by parasitic protozoans, such as a Plasmodium parasite, or parasitic helminths.

Uses of parasite macrophage migration inhibitory factors

Managing COVID-19 going forward—the lessons from history R. Bucala, G. Friedland and F. M. Snowden From the Department of Medicine, Yale School of Medicine, New Haven, CT, USA, Department of Pathology, Yale School of Medicine, New Haven, CT, USA, Department of Epidemiology & Public Health, Yale School of Medicine, New Haven, CT, USA and Department of History and History of Medicine, Yale University, New Haven, CT, USA

/pdf/managing-covid-19-going-forward-the-lessons-from-history-36lnsz86.pdf

Managing COVID-19 going forward—the lessons from history

Regulation of expression of CTL activity by macrophage migration inhibitory factor (MIF) is disclosed. In a mouse model using the EL4 tumor, cultured splenocytes from tumor-primed mice secrete high levels of MIF following antigen stimulation in vitro. Parallel splenocytes treated with neutralizing anti-MIF mAb showed a significant increase in CTL response against tumor cells compared to control mAb-treated cultures, with elevated expression of IFN gamma . Histology of tumors from anti-MIF treated animals showed increases in infiltration of both CD4 and CD8 T cells, as well as apoptotic tumor cells, consistent with observed augmentation of CTL activity in vivo by anti-MIF, which was associated with enhanced expression of the common gamma c chain of the IL-2 receptor that mediates CD8 T cell survival. CD8 cells of anti-MIF treated tumor-bearing mice showed increased migration into tumors of control mice. Methods for enhancing a CTL response by inhibition of MIF are disclosed.

Regulation of the cytotoxic lymphocyte response by macrophage migration inhibitory factor

Psychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators.The perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded.Seventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks.MBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH.This study is registered at ClinicalTrials.gov (NCT02950077).Autoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis. 

http://www.jhep-reports.eu/article/S2589555922000222/pdf

Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis

In this issue of Arthritis & Rheumatology (A&R), Sieper and colleagues report the results of an important trial demonstrating the benefits of a tumor necrosis factor (TNF) antagonist for the treatment of nonradiographic spondyloarthritis (1). As optimal treatment for this condition evolves, well-designed randomized controlled trials (RCTs) will play a pivotal role in defining the standard of care for one of the more common inflammatory arthritides. We highlight this study not only because of its importance to rheumatology but also because of the vital role of RCTs in A&R. Throughout the 57-year history of A&R, RCTs have always played a prominent role. Major advances in our understanding of treatment, pathobiology, the mechanisms of action of a treatment, and new avenues of scientific investigation are facilitated by RCTs. Some of the major RCTs published in A&R throughout the many decades document the roles of TNF antagonists in rheumatoid arthritis (2,3), cyclophosphamide and belimumab in systemic lupus erythematosus (4,5), nonpharmacologic therapies in osteoarthritis (6,7), novel therapies in gout (8,9), and various treatments in vasculitis (10,11) With this issue, which begins the tenure of the new editorial team, we rededicate Arthritis & Rheumatology to the goal of publishing the most important RCTs in our field. The importance of RCTs in A&R is reflected by a new section of the journal that is dedicated to RCTs, with one of us (MEW), a senior clinical trials investigator, as the section advisor. As with the RCT published in the current issue (1), A&R will now offer fast-track reviews. For example, the total review time for the article by Sieper and colleagues (1), from submission to acceptance, was 20 days. Authors of RCTs desiring a fast-track review need to contact the Editor in Chief (RJB) or Deputy Editor (DHS) at least 14 days prior to submission to facilitate such a review. The new section will focus on phase I, phase II, and phase III RCTs. A phase III RCT using approved drugs for new indications, such as that reported by Sieper and colleagues, will also be considered for this section and for fast-track review. Nonrandomized phase IV studies will be published in other sections of the journal, and phase I and phase II studies will typically not receive fast-track status, except under circumstances in which the findings are exceptionally noteworthy. In addition, A&R embraces the important role of effectiveness studies in the current research milieu. Efficacy studies (how interventions work in idealized settings, such as an RCT) and effectiveness studies (how interventions work in typical settings, such as registries and pragmatic controlled clinical trials) contribute complementary and critical information for determining best practice. RCTs with negative results also provide important information for drug developers, providers, and patients that will be embraced by this journal. Dr. Solomon’s work was supported in part by research grants to Brigham and Women’s Hospital from Amgen, Lilly, Pfizer, AstraZeneca, and CORRONA. Daniel H. Solomon, MD, MPH (Deputy Editor, A&R), Michael E. Weinblatt, MD (Clinical Trials Advisor, A&R): Brigham and Women’s Hospital, Boston, Massachusetts; Richard J. Bucala, MD, PhD (Editor in Chief, A&R): Yale University School of Medicine, New Haven, Connecticut. Dr. Weinblatt has received consulting fees from AbbVie, Ablynx, Amgen, AstraZeneca, Bristol-Myers Squibb, Can-Fite BioPharma, Catabasis, Compugen, CORRONA, Crescendo Bioscience, Ensemble Therapeutics, Exagen Diagnostics, Five Prime Therapeutics, Genentech/Roche, Idera, Infinity, Lycera, Lilly, MedImmune, Merck, Novartis, Pfizer, Principia Biopharma, Receptos, Regeneron, Samsung, Sanofi, and UCB (less than $10,000 each) and grants from Bristol-Myers Squibb, Crescendo Bioscience, and UCB. Dr. Bucala is a named inventor on, and has received royalties from, licensed patents in the area of macrophage migration inhibitory factor therapeutics and owns equity in Promedior and MIFCOR. Address correspondence to Daniel H. Solomon, MD, MPH, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, 75 Francis Street, PBB-B3, Boston, MA 02115. E-mail: dsolomon@partners.org. Submitted for publication June 15, 2015; accepted in revised form June 18, 2015.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/art.39258

Richard Bucala

Papers

Uses of parasite macrophage migration inhibitory factors

Managing COVID-19 going forward—the lessons from history

Regulation of the cytotoxic lymphocyte response by macrophage migration inhibitory factor

Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis

Editorial: the vital role of randomized controlled trials in Arthritis & Rheumatology.