Infections, atherosclerosis, and coronary heart disease.

Atherosclerosis is a chronic inflammatory disease. Pathophysiological similarities between chronic infections and atherosclerosis triggered interest in a clinical association between these conditions. Various infectious microbes have been linked to atherosclerotic vascular disease in epidemiological studies. However, this association failed to satisfy the Koch's postulates of causation with multiple clinical trials demonstrating inefficacy of anti-infective therapies in mitigating atherosclerotic cardiovascular events. Identification of underlying pathophysiological mechanisms and experience with vaccination against various infectious agents has ushered a new avenue of efforts in the development of an anti-atherosclerotic vaccine. Studies in animal models have identified various innate and adaptive immune pathways in atherosclerosis. In this review, we discuss the patho-biological link between chronic infections and atherosclerosis, evaluate existing evidence of animal and human trials on the association between infections and cardiovascular disease and introduce the concept of an anti-atherosclerotic vaccine

How the field of infectious diseases can leverage digital strategy and social media use during a pandemic

Rapid information dissemination is critical in a world changing rapidly due to global threats. Ubiquitous internet access has created new methods of information dissemination that are rapid, far-reaching, and universally accessible. However, inaccuracies may accompany rapid information dissemination, and rigorous evaluation of primary data through various forms of peer review is crucial. In an era in which high-quality information can save lives, it is critical that infectious diseases specialists are well versed in digital strategy to effectively disseminate information to colleagues and the community and diminish voices spreading misinformation. In this study, we review how social media can be used for rapid dissemination of quality information, benefits and pitfalls of social media use, and general recommendations for developing a digital strategy as an infectious diseases specialist. We will describe how the Infectious Diseases Society of America has leveraged digital strategy and social media and how individuals can amplify these resources to disseminate information, provide clinical knowledge, community guidance, and build their own person brand. We conclude in providing guidance to infectious diseases specialists in aiming to build and preserve public trust, consider their audience and specific goals, and use social media to highlight the value of the field of infectious diseases

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

What if negative emission technologies fail at scale? : Implications of the Paris Agreement for big emitting nations

A cumulative emissions approach is increasingly used to inform mitigation policy. However, there are different interpretations of what 2 degrees C' implies. Here it is argued that cost-optimization models, commonly used to inform policy, typically underplay the urgency of 2 degrees C mitigation. The alignment within many scenarios of optimistic assumptions on negative emissions technologies (NETs), with implausibly early peak emission dates and incremental short-term mitigation, delivers outcomes commensurate with 2 degrees C commitments. In contrast, considering equity and socio-technical barriers to change, suggests a more challenging short-term agenda. To understand these different interpretations, short-term CO2 trends of the largest CO2 emitters, are assessed in relation to a constrained CO2 budget, coupled with a what if' assumption that negative emissions technologies fail at scale. The outcomes raise profound questions around high-level framings of mitigation policy. The article concludes that applying even weak equity criteria, challenges the feasibility of maintaining a 50% chance of avoiding 2 degrees C without urgent mitigation efforts in the short-term. This highlights a need for greater engagement with: (1) the equity dimension of the Paris Agreement, (2) the sensitivity of constrained carbon budgets to short-term trends and (3) the climate risks for society posed by an almost ubiquitous inclusion of NETs within 2 degrees C scenarios.POLICY RELEVANCESince the Paris meeting, there is increased awareness that most policy solutions' commensurate with 2 degrees C include widespread deployment of negative emissions technologies (NETs). Yet much less is understood about that option's feasibility, compared with near-term efforts to curb energy demand. Moreover, the many different ways in which key information is synthesized for policy makers, clouds the ability of policy makers to make informed decisions. This article presents an alternative approach to consider what the Paris Agreement implies, if NETs are unable to deliver more carbon sinks than sources. It illustrates the scale of the climate challenge for policy makers, particularly if the Agreement's aim to address equity' is accounted for. Here it is argued that much more attention needs to be paid to what CO2 reductions can be achieved in the short-term, rather than taking a risk that could render the Paris Agreement's policy goals unachievable