Advanced nursing practice and research contributions to precision medicine

Genomic discoveries in the era of precision medicine hold the promise for tailoring healthcare, symptom management, and research efforts including targeting rare and common diseases through the identification and implementation of genomic-based risk assessment, treatment, and management. However, the translation of these discoveries into tangible benefits for the health of individuals, families, and the public is evolving.; In this article, members of the Genetics Expert Panel identify opportunities for action to increase advanced practice nursing and research contributions toward improving genomic health for all individuals and populations.; Identified opportunities are within the areas of: bolstering genomic focused advanced practice registered nurse practice, research and education efforts; deriving new knowledge about disease biology, risk assessment, treatment efficacy, drug safety and self-management; improving resources and systems that combine genomic information with other healthcare data; and advocating for patient and family benefits and equitable access to genomic healthcare resources

Precision health: A nursing perspective

Precision health refers to personalized healthcare based on a person's unique genetic, genomic, or omic composition within the context of lifestyle, social, economic, cultural and environmental influences to help individuals achieve well-being and optimal health. Precision health utilizes big data sets that combine omics (i.e. genomic sequence, protein, metabolite, and microbiome information) with clinical information and health outcomes to optimize disease diagnosis, treatment and prevention specific to each patient. Successful implementation of precision health requires interprofessional collaboration, community outreach efforts, and coordination of care, a mission that nurses are well-positioned to lead. Despite the surge of interest and attention to precision health, most nurses are not well-versed in precision health or its implications for the nursing profession. Based on a critical analysis of literature and expert opinions, this paper provides an overview of precision health and the importance of engaging the nursing profession for its implementation. Other topics reviewed in this paper include big data and omics, information science, integration of family health history in precision health, and nursing omics research in symptom science. The paper concludes with recommendations for nurse leaders in research, education, clinical practice, nursing administration and policy settings for which to develop strategic plans to implement precision health

Collection and storage of human blood and adipose for genomic analysis of clinical samples

In this methods article, we describe collection and storage of clinically acquired blood and adipose samples for transcript analysis in an ongoing study exploring obesity in renal transplant recipients. Total ribonucleic acid (RNA) was isolated from whole blood using the LeukoLOCK™ Total RNA Isolation System (n=4), and comparisons between fresh and frozen samples were made. Abdominal subcutaneous adipose samples (n=4) were obtained during kidney transplantation, flash frozen, and stored at -80°C. Adipose RNA was extracted using either the STAT-60 method modified for lipids or Trizol plus RNeasy extraction. Affymetrix HG-U133 plus 2.0 arrays and Affymetrix Human Gene 1.0 ST arrays were used for both blood and adipose transcriptome analysis. Purity, quality, and quantity of RNA were high with comparable results using both array platforms. © 2011 Wiley Periodicals, Inc

Food availability as a determinant of weight gain among renal transplant recipients

Excessive weight gain is common after renal transplantation, but it is unknown whether environmental factors, such as food availability, contribute to this important clinical problem. We evaluated the effects of food availability (fast food restaurants, convenience stores, and grocery stores within 1, 2, and 3 mile buffers of transplant recipients\u27 residences) on body mass index (BMI) change during the first year post-transplant. Participants (n=299) resided in Memphis, Tennessee. BMI increased by 1.42 units (p\u3c.001) corresponding to an average weight gain of 9.25lbs (5.43%) during the first year post-transplant. The number of grocery stores within 1 mile of recipient\u27s residence was associated with an increase in BMI (p\u3c.05), but fast food restaurants and convenience stores were not significantly associated with BMI change. © 2014 Wiley Periodicals, Inc

Exaggerated plasma interleukin 6, interleukin 10, and subsequent development of health care-associated infections in patients with sepsis

BACKGROUND: Health care-associated infections (HAIs) are the target of many well-known preventive measures in the intensive care unit (ICU); however, little is known about post-sepsis-induced immunosuppression. OBJECTIVES: This study explores the relationship between baseline plasma levels of inflammatory cytokines interleukin 6 (IL-6), IL-10, and IL-6:IL-10 and subsequent development of HAIs in patients with admitted with sepsis. METHODS: Prospective observational study was conducted among veterans admitted to the ICU with sepsis and monitored daily through ICU discharge (up to 28 days) to investigate HAI development. Baseline plasma IL-6 and IL-10 levels were measured with a multiplex bead based assay. Exaggerated systemic inflammation was defined as the fourth quartile (IL-6 and IL-10) compared with other quartiles. RESULTS: We recruited 78 patients over 18 months, primarily older (65.5 ± 12.6 years) men (94.9%) with underlying comorbidities (93.9%) and a high severity of illness (Acute Physiologic and Chronic Health Evaluation II score 20.6 ± 6.4). Seventeen patients (21.7%) developed at least 1 HAI, and candidemia was the leading infection. Patients with exaggerated baseline systemic inflammation developed a nonsignificantly higher proportion of HAI as compared with those not developing HAI (IL-6: 31.6% vs 18.6%, P = .55; IL-10: 26.3% vs 20.3%, P = .43). DISCUSSION: Patients with exaggerated systemic inflammation had a higher severity of illness, but not a statistically significant higher incidence of HAI. A larger, more adequately powered sample with serial cytokine measures is needed. Routine surveillance cultures are needed. Health care-associated infection may occur in the absence of fever, and the emerging incidence of Candida is a concern. Immune suppression after sepsis should be recognized as a risk for HAI development. Antibiotic therapy should be targeted with prompt de-escalation of empiric therapy per established guidelines to preserve normal flora

Hit-to-Lead Optimization and Discovery of 5‑((5-([1,1′-Biphenyl]-4-yl)-6-chloro‑1<i>H</i>‑benzo[<i>d</i>]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase

AMP-activated protein kinase (AMPK) plays an essential role as a cellular energy sensor and master regulator of metabolism in eukaryotes. Dysregulated lipid and carbohydrate metabolism resulting from insulin resistance leads to hyperglycemia, the hallmark of type 2 diabetes mellitus (T2DM). While pharmacological activation of AMPK is anticipated to improve these parameters, the discovery of selective, direct activators has proven challenging. We now describe a hit-to-lead effort resulting in the discovery of a potent and selective class of benzimidazole-based direct AMPK activators, exemplified by 5-((5-([1,1′-biphenyl]-4-yl)-6-chloro-1<i>H</i>-benzo­[<i>d</i>]­imidazol-2-yl)­oxy)-2-methylbenzoic acid, <b>42</b> (MK-3903). Compound <b>42</b> exhibited robust target engagement in mouse liver following oral dosing, leading to improved lipid metabolism and insulin sensitization in mice