Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition but also an overabundance of genomic virulence factors that have functional consequence on host immune evasion. IMPORTANCE Older adults suffer more frequent and worse outcomes from sepsis, a critical illness secondary to infection. The reasons underlying this unique susceptibility are incompletely understood. Prior work in this area has focused on how the immune response changes with age. The current study, however, focuses instead on alterations in the community of bacteria that humans live with within their gut (i.e., the gut microbiome). The central concept of this paper is that the bacteria in our gut evolve along with the host and "age," making them more efficient at causing sepsis.

Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host, but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition, but an overabundance of genomic virulence factors that have functional consequence on host immune evasion. One Sentence Summary: The severity of sepsis in the aged host is in part mediated by longevity-associated increases in gut microbial virulence.

Cardiac Toxicity and Anthracyclines: Mechanism, Interventions, and the Trouble With Troponin.

As cancer survivorship increases, clinicians need to become educated regarding the long-term effect of cancer treatments. Cancer therapeutics-related cardiac dysfunction (CTRCD) is one such sequela that contributes to significant morbidity and mortality. Unfortunately, screening and management practices regarding CTRCD are inconsistent within guidelines and practice. This review will first look at anthracycline-related cardiac dysfunction occurrence and pathophysiology. Current guidelines for CTRCD screening will be discussed, including the use of 2D echocardiograms along with newer technology such as 3D echocardiography and global systolic longitudinal myocardial strain (GLS) measurements. Biomarkers like serum troponin demonstrate promise as an early indicator of cardiomyocyte injury and a potential means of risk stratification; however, guidelines vary regarding how best to incorporate elevated serum troponin levels into management plans. Growing evidence indicates the clinical need for early detection of CTRCD in order to initiate preventative pharmacologic management and improve patient outcomes.

Walking the red road: the role of First Nations grandparents in promoting cultural well-being.

The purpose of this grounded theory study was to provide a framework for understanding the contemporary experience of First Nations grandparents. Fifteen respondents (N = 15) were selected from two demographically different Canadian cities. Seven of the grandparents lived with their child and a grandchild or grandchildren at the time of the interview; an additional four had lived with their grandchildren at some point prior to this investigation. Results revealed that First Nations grandparents had leveraged their own experiences of cultural disruption to reinvest in the cultural health and well-being of their grandchildren. One grandfather described this role as "walking the red road" which entailed a responsibility "to provide wisdom- and ... protection." Identified benefits of rejuvenating traditions and grandparent involvement included cultural healing and joy.