Anticomplement therapy

Prathit A Kulkarni1, Vahid Afshar-Kharghan21Baylor College of Medicine, Houston, Texas, USA; 2The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USAAbstract: The complement system is an important part of innate immunity; however, as with other parts of the immune system, the complement system can become pathologically activated and create or worsen disease. Anticomplement reagents have been studied for several years, but only recently have they emerged as a viable therapeutic tool. Here, we describe the role of the complement system in a wide array of diseases, as well as the use of anticomplement therapy as treatment for these diseases in animal models and in human clinical trials. Specifically, we will discuss the role of anticomplement therapy in paroxysmal nocturnal hemoglobinuria, glomerulonephritis, and heart disease, including coronary artery disease, myocardial infarction, and coronary revascularization procedures such as percutaneous coronary angioplasty and coronary artery bypass graft surgery.Keywords: complement, paroxysmal nocturnal hemoglobinuria, glomerulonephritis, myocardial infarction, cardiopulmonary bypas

Serogroup B Meningococcal Disease Vaccine Recommendations at a University, New Jersey, USA, 2016

In response to a university-based serogroup B meningococcal disease outbreak, the serogroup B meningococcal vaccine Trumenba was recommended for students, a rare instance in which a specific vaccine brand was recommended. This outbreak highlights the challenges of using molecular and immunologic data to inform real-time response

Education of Infectious Diseases Fellows During the COVID-19 Pandemic Crisis: Challenges and Opportunities

One of the many challenges that has befallen the Infectious Diseases and Graduate Medical Education communities during the coronavirus disease 2019 (COVID-19) pandemic is the maintenance of continued effective education and training of the future leaders of our field. With the remarkable speed and innovation that has characterized the responses to this pandemic, educators everywhere have adapted existing robust and safe learning environments to meet the needs of our learners. This paper will review distinct aspects of education and training of the Infectious Diseases fellows we believe the COVID-19 pandemic has impacted most, including mentoring, didactics, and wellness. We anticipate that several strategies developed in this context and described herein will help to inform training and best practices during the pandemic and beyond

Activation of cardiac Cdk9 represses PGC-1 and confers a predisposition to heart failure

Hypertrophy allows the heart to adapt to workload but culminates in later pump failure; how it is achieved remains uncertain. Previously, we showed that hypertrophy is accompanied by activation of cyclin T/Cdk9, which phosphorylates the C-terminal domain of the large subunit of RNA polymerase II, stimulating transcription elongation and pre-mRNA processing; Cdk9 activity was required for hypertrophy in culture, whereas heart-specific activation of Cdk9 by cyclin T1 provoked hypertrophy in mice. Here, we report that αMHC-cyclin T1 mice appear normal at baseline yet suffer fulminant apoptotic cardiomyopathy when challenged by mechanical stress or signaling by the G-protein Gq. At pathophysiological levels, Cdk9 activity suppresses many genes for mitochondrial proteins including master regulators of mitochondrial function (peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), nuclear respiratory factor-1). In culture, cyclin T1/Cdk9 suppresses PGC-1, decreases mitochondrial membrane potential, and sensitizes cardiomyocytes to apoptosis, effects rescued by exogenous PGC-1. Cyclin T1/Cdk9 inhibits PGC-1 promoter activity and preinitiation complex assembly. Thus, chronic activation of Cdk9 causes not only cardiomyocyte enlargement but also defective mitochondrial function, via diminished PGC-1 transcription, and a resulting susceptibility to apoptotic cardiomyopathy

The Struggling Infectious Diseases Fellow: Remediation Challenges and Opportunities.

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges