Biological Research For Nursing

Incorporating biologically based data into symptom science research can contribute substantially to understanding commonly experienced symptoms across chronic conditions. The purpose of this literature review was to identify functional polymorphisms associated with common symptoms (i.e., pain, sleep disturbance, fatigue, affective and cognitive symptoms) with the goal of identifying a parsimonious list of functional genetic polymorphisms with evidence to advocate for their inclusion in symptom science research. PubMed was searched to identify genes and functional polymorphisms associated with symptoms across chronic conditions, revealing eight functional genetic polymorphisms in seven different genes that showed evidence of association with at least three or more symptoms and/or symptom clusters: BDNF rs6265, COMT rs4680, FKBP5 rs3800373, IL-6 rs1800795, NFKB2 rs1056890, SLC6A4 5-HTTLPR+rs25531, and TNFA rs1799964 and rs1800629. Of these genes, three represent protein biomarkers previously identified as common data elements for symptom science research (BDNF, IL-6, and TNFA), and the polymorphisms in these genes identified through the search are known to impact secretion or level of transcription of these protein biomarkers. Inclusion of genotype data for polymorphisms offers great potential to further advance scientific knowledge of the biological basis of individual symptoms and symptom clusters across studies. Additionally, these polymorphisms have the potential to be used as targets to optimize precision health through the identification of individuals at risk for poor symptom experiences as well as the development of symptom management interventions.

Delirium is a serious complication of acute illness. Little is known, however, regarding the neurobiology of delirium, largely due to challenges in studying the complex inpatient population. Neuroimaging is one noninvasive method that can be used to study structural and functional brain abnormalities associated with delirium. The purpose of this integrative literature review was to examine the content and quality of current structural neuroimaging evidence in delirium. After meeting inclusion criteria, 11 articles were included in the review. Commonly noted structural abnormalities were impaired white matter integrity, brain atrophy, ischemic lesions, edema, and inflammation. Findings demonstrated widespread alterations in several brain structures. Limitations of the studies in this review included small sample sizes, inappropriate or questionable delirium measurements, and failure to consider confounding variables. This review provides insight into possible structural changes responsible for the signs and symptoms seen in patients with delirium, but more high-quality studies are needed.

Preterm infants are at risk of brain injury and poor neurodevelopmental outcomes including impairments in cognition, behavioral functioning, sensory perception, and motor performance. Systemic inflammation has been identified as an important, potentially modifiable precursor of neurologic and neurodevelopmental impairments. Inflammation is typically measured by quantifying circulating cytokines and chemokines. However, it is unclear which specific cytokines/chemokines most consistently predict neurodevelopment in preterm infants. In this integrative review, we evaluated and analyzed the literature (N = 37 publications) to determine the cytokines/chemokines most predictive of neurodevelopment in preterm infants, the optimal timing for these measurements, and the ideal source for collecting cytokines/chemokines. Synthesis of the findings of these studies revealed that interleukin (IL)-6, IL-1β, IL-8, and tumor necrosis factor (TNF)-α collected during the first 3 weeks of life are most predictive of subsequent neurodevelopment. Methodological variation among studies hinders more specific analysis, including the evaluation of cytokine thresholds and meta-analyses, that would allow for the use of cytokines/chemokines to predict neurodevelopment. Future research should focus on identifying explicit cytokine values, specifically for IL-6, IL-1β, IL-8, and TNF-α, that are most predictive for identifying preterm infants most at risk of impairment, keeping in mind that longitudinal measures of cytokines/chemokines may be more predictive of future outcomes than single-time point measures.

Adolescents with obesity and obstructive sleep apnea syndrome (OSAS) are at high risk of poor physical and cognitive health consequences. The purpose of this study was to explore executive function (EF) in adolescents with obesity and OSAS, describe physical activity and sleep duration, and explore the relationships between EF and physical activity and sleep duration. Participants comprised 20 adolescents (ages 11–17 years) with obesity (body mass index [BMI] ≥ 95th percentile) and OSAS (apnea–hypopnea index [AHI] ≥ 1.5 events/hr) participated in this observational pilot study with a prospective 1-week measurement protocol. Outcome measures included EF by the Behavior Rating Inventory of Executive Function-2, physical activity by Previous Day Physical Activity Recall, and sleep by Consensus Sleep Diary and actigraphy. Adolescents with obesity and OSAS had significantly worse EF by self- and parent-report than the normative sample (p ≤ .003), 45% had impaired EF and up to 30% had clinically significant impairments. Participants spent approximately 14.3 hr/day in light-intensity activity, and 33% did not engage in moderate-to-vigorous-intensity activity for at least 60 min on any days of data collection. Adolescents had insufficient sleep duration, averaging 6.9 hr/night. No significant relationships were identified between physical activity or sleep duration and EF. Providers should have a heightened awareness for EF impairments in obese adolescents with OSAS and consider how EF deficits may affect uptake and adherence to complex lifestyle and/or medical interventions among these patients.

Type 2 diabetes (T2D) is a highly prevalent metabolic disease, affecting nearly 10% of the American population. Although the etiopathogenesis of T2D remains poorly understood, advances in DNA sequencing technologies have allowed for sophisticated interrogation of the human microbiome, providing insight into the role of the gut microbiome in the development and progression of T2D. An emerging body of research reveals that gut–brain axis (GBA) perturbations and a high-fat diet (HFD), along with other modifiable and nonmodifiable risk factors, contribute to gut microbiome homeostatic imbalance. Homeostatic imbalance or disruption increases gut wall permeability and facilitates translocation of endotoxins (lipopolysaccharides) into the circulation with resultant systemic inflammation. Chronic, low-grade systemic inflammation ensues with pro-inflammatory pathways activated, contributing to obesity, insulin resistance (IR), pancreatic β-cell decline, and, thereby, T2D. While GBA perturbations and HFD are implicated in provoking these conditions, prior mechanistic models have tended to examine HFD and GBA pathways exclusively without considering their shared pathways to T2D. Addressing this gap, this article proposes a mechanistic model informed by animal and human studies to advance scientific understanding of (1) modifiable and nonmodifiable risk factors for gut microbiome homeostatic disruption, (2) HFD and GBA pathways contributing to homeostatic disruption, and (3) shared GBA and HFD pro-inflammatory pathways to obesity, IR, β-cell decline, and T2D. The proposed mechanistic model, based on the extant literature, proposes a framework for studying the complex relationships of the gut microbiome to T2D to advance study in this promising area of research.

Osteoarthritis (OA) is the most common cause of pain in people aged >45 years, and the knee is the most commonly affected joint. There is a growing interest in understanding the biological factors that influence pain among older adults, but few studies have examined the relationship between β-endorphin and experimental pain sensitivity in older adults with knee OA pain. The purpose of this study was to investigate the relationship between resting plasma levels of β-endorphin and experimental pain sensitivity. This study was a secondary analysis of data for 40 adults with knee OA pain in whom quantitative sensory testing was used to measure experimental sensitivity to heat- and mechanically induced pain. The mean age of the sample was 60 years (SD = 9 years), and approximately half were female (53%). Regression analyses indicated that β-endorphin level was negatively related to pressure pain threshold (β = −17.18, p = .02) and positively related to punctate mechanical pain (β = 17.13, p = .04), after controlling for age, gender, and OA severity. We did not find a significant relationship between β-endorphin and heat pain tolerance. The results suggest that higher circulating levels of β-endorphin at rest are associated with increased sensitivity to mechanical pain in older adults with knee OA. These findings add to the literature regarding biological factors associated with pain sensitivity in older adults with chronic pain. Additional studies are needed to identify mediators of the relationship between β-endorphin and pain sensitivity in OA and other musculoskeletal pain conditions.

The prevalence and incidence of chronic venous leg ulcers (CVLUs) are increasing worldwide, as are the associated financial costs. Although it has long been known that their underlying etiology is venous insufficiency, the molecular aspects of healing versus nonhealing, as well as the psychoneurologic symptoms (PNS; pain, cognitive dysfunction, fatigue, depression, and anxiety) associated with CVLUs remain understudied. In this biobehaviorally focused review, we aim to elucidate the complex mechanisms that link the biological and molecular aspects of CLVUs with their PNS. Innovations in “omics” research have increased our understanding of important wound microenvironmental factors (e.g., inflammation, microbial pathogenic biofilm, epigenetic processes) that may adversely alter the wound bed’s molecular milieu so that microbes evade immune detection. Although these molecular factors are not singularly responsible for wound healing, they are major components of wound development, nonhealing, and PNS that, until now, have not been amenable to systematic study, especially over time. Further, this review explores our current understanding of the molecular mechanisms by which the immune activation that contributes to the development and persistence of CVLUs also leads to the development, persistence, and severity of wound-related PNS. We also make recommendations for future research that will expand the field of biobehavioral wound science. Biobehavioral research that focuses on the interrelated mechanisms of PNS will lead to symptom-management interventions that improve quality of life for the population burdened by CVLUs.

Wound healing is severely affected in hyperglycemia and other metabolic conditions. Finding new therapeutic approaches that accelerate wound healing and improve the quality of the scar may reduce the morbidity commonly associated with skin lesions in diabetes. This study evaluated the effect of topical topiramate (TPM) on wound healing in C57 mice. Streptozotocin-induced hyperglycemic mice were subjected to a wound on the back and randomly allocated for treatment with either vehicle or topical TPM cream (2%) once a day for 14 days. Polymerase chain reaction, Western blotting, and microscopy were performed for the analysis. TPM improved wound healing (complete resolution at Day 10, 98% ± 5 for TPM vs. 81% ± 28 for vehicle), increased organization and deposition of collagen Type I, and enhanced the quality of the scars as determined by microscopy. In addition, TPM modulated the expression of cytokines and proteins of the insulin-signaling pathway: In early wound-healing stages, expression of interleukin-10, an anti-inflammatory marker, increased, whereas at the late phase, the pro-inflammatory markers tumor necrosis factor-α and monocyte chemoattractant protein-1 increased and there was increased expression of a vascular endothelial growth factor. Proteins of the insulin-signaling pathway were stimulated in the late wound-healing phase. Topical TPM improves the quality of wound healing in an animal model of hyperglycemia. The effect of TPM is accompanied by modulation of inflammatory and growth factors and proteins of the insulin-signaling pathway. Therefore, topical TPM presents as a potential therapeutic agent in skin wounds in patients with hyperglycemia.