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Introduction: The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of kidney injury have the potential to detect cellular stress and damage in real time. Methods: To detect the response of the kidney to injury, we have tested a lateral flow dipstick that measures a urinary protein called neutrophil gelatinase-associated lipocalin (NGAL). Analysis of urine was performed in a prospective cohort of 479 patients (final cohort N ¼ 426) entering an emergency department in New York City and subsequently admitted for inpatient care. Results: Colorimetric development had high interrater reliability (88% concordance rate) and correlated with traditional enzyme-linked immunosorbent assay (ELISA) measurements (r ¼ 0.732, P < .0001). Of the 14% of the cohort who met Acute Kidney Injury Network (AKIN) SCr criteria for acute kidney injury (AKI), 67% demonstrated transient (<2 days) and 33% demonstrated sustained (>2 days) elevation of SCr. Comparing the outcomes of patients with sustained versus transient or undetectable changes in SCr revealed that the urinary NGAL (uNGAL) dipstick had high specificity and negative predictive value (NPV) (high-vs. low-intermediate readings, sensitivity ¼ 0.55, specificity ¼ 0.91, positive predictive value ¼ 0.24, NPV ¼ 0.97, c 2 ¼ 20.39, P < 0.001). Conclusion: We show that the introduction of a bedside uNGAL dipstick permits accurate triage by identifying individuals who do not have tubular injury. In an era of shortening length of stay and rapid decisions based on isolated SCr measurements, real-time exclusion of kidney injury by a dipstick will be particularly useful to overcome the retrospective, insensitive, and nonspecific attributes of SCr.

Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses.The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6-to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline-versus vehicle-treated germfree mice had similar alveolar bone loss outcomes, implying that antimicrobialdriven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring

Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by seven-fold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation post-MI through memory T-cell activation. We compared 4 groups (no MI, chronic LPS, day 1 post-MI, and day 1 post-MI with chronic LPS (LPS+MI); n=68 mice) using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS+MI increased total CD8+ T-cells in the left ventricle versus the other groups (p<0.05 versus all). Memory CD8+ T-cells (CD44+CD27+) were 10-fold greater in LPS+MI compared to MI alone (p=0.02). Interleukin (IL)-4 stimulated splenic CD8+ T-cells away from an effector phenotype and towards a memory phenotype, inducing secretion of factors associated with the Wnt/β-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8+ T-cells post-MI, we administered a major histocompatibility complex-I blocking antibody starting 7 days before MI, which prevented effector CD8+ T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS+MI+IgG attenuated macrophages within the infarct without effecting CD8+ T-cells suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8+ T-cells at post-MI day 1 are amplified by chronic LPS to potentially promote infarct wall thinning.

During homeostasis, immune cells perform daily housekeeping functions to maintain heart health by acting as sentinels for tissue damage and foreign particles. Resident immune cells compose 5% of the cellular population in healthy human ventricular tissue. In response to injury, there is an increase in inflammation within the heart due to the influx of immune cells. Some of the most common immune cells recruited to the heart are macrophages, dendritic cells, neutrophils, and T-cells. In this review, we will discuss what is known about cardiac immune cell heterogeneity during homeostasis, how these cell populations change in response to a pathology such as myocardial infarction or pressure overload, and what stimuli are regulating these processes. In addition, we will summarize technologies used to evaluate cell heterogeneity in models of cardiovascular disease.