Background: Severe pain is among the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD), of whom more than 50% report chronic pain. Despite this, the understanding of the biological contributors to persistent severe SCD pain is limited. This exploratory study sought to describe pain phenotypes based on frequency of severe pain experienced over 6 months and identify inflammatory biomarkers associated with pain phenotypes among individuals with SCD.
Methods: This study used self-report and electronic health record data collected from 74 individuals enrolled in the Duke Sickle Cell Disease Implementation Consortium Registry. Plasma from previously collected blood specimens was used to generate inflammatory biomarker data using the Inflammation 20-plex ProcartaPlexTM panel. Descriptive statistics were used to describe the occurrence of severe pain over the past 6 months, and bi-variate analyses were used to evaluate the relationship between inflammatory biomarkers and pain phenotypes.
Results: Among the 74 participants included in this study, 33.8% reported severe pain occurring never or rarely, 40.5% reported severe pain occurring sometimes, and 25.7% reported severe pain occurring often or always. Soluble E-selectin (sE-selectin) was the only inflammatory biomarker significantly associated with the pain phenotype groups (p = 0.049). Post hoc comparisons identified that participants in the often/always severe pain group had significantly higher plasma concentrations of sE-selectin compared to those in the sometimes severe pain group (p = 0.040).
Conclusions: Our findings provide preliminary evidence of the frequent occurrence of severe pain and that sE-selectin may be an objective biomarker for the frequent occurrence of severe pain in this population.
Background: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations.
Materials and methods: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance.
Results: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents.
Conclusion: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads.
Objective: To examine glycemic variability within 1 month and 1 year following surgery among adult patients, with and without Type 2 Diabetes (T2D), treated for stage II-III colon cancer.
Method: A retrospective analysis of electronic health record data was conducted. Glycemic variability (i.e., standard deviation [SD] and coefficient of variation [CV] of > 2 blood glucose measures) was assessed within 1 month and within 1 year following colon surgery. Chi-square (χ2), Fisher's exact, and Mann-Whitney U tests were used for the analyses.
Results: Among the sample of 165 patients with stage II-III colon cancer, those with T2D had higher glycemic variability compared to patients without T2D (p < .001), with values within 1 month following surgery (SD = 44.69 mg/dL, CV = 27.4%) vs (SD = 20.55 mg/dL, CV = 17.53%); and within 1 year following surgery (SD = 45.04 mg/dL, CV = 29.04%) vs (SD = 21.36 mg/dL, CV = 18.6%). Associations were found between lower body mass index and higher glycemic variability (i.e., SD [r = -.413, p < .05] and CV [r = -.481, p < .01]) within 1 month following surgery in patients with T2D. Higher preoperative glucose was associated with higher glycemic variability (i.e., SD r = .448, p < .01) within 1 year in patients with T2D. Demographic and clinical characteristics were weakly associated with glycemic variability in patients without T2D.
Conclusions: Patients with stage II-III colon cancer with T2D experienced higher glycemic variability within 1 month and within 1 year following surgery compared to those without T2D. Associations between glycemic variability and demographic and clinical characteristics differed by T2D status. Further research in prospective studies is warranted.
Osteoporosis is a common comorbidity in patients with systemic lupus erythematosus (SLE), but the potential contribution of disease-associated factors to bone status in SLE is not well known because the reported risk factors from different studies differ greatly. We aimed to examine frequency of reduced bone mass in women with SLE, and determine their potential associations with disease activity, damage accrual and SLE-related clinical markers. A cross-sectional study including 121 Caucasian pre-menopausal and postmenopausal women was conducted (mean age 49.2 ± 12.4 years). The SLE Disease Activity Index (SLEDAI-2 K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. Bone mineral density (BMD) of the left femoral neck and lumbar spine (L2-L4) were measured by dual-energy X-ray absorptiometry. Ten patients (8.3%) had osteoporosis, 63 (52.1%) patients had osteopenia and 6.8% of women had history of previous fracture. Patients with low bone mass had a significantly higher mean SDI (1.3 ± 1.2 versus 0.7 ± 1.0 p = 0.003). T-score at lumbar spine was inversely correlated with SDI score (r = -0.222, p = 0.014) and complement C3 level (r = -0.206, p = .024). SDI scores were significantly different between patients with osteoporosis, osteopenia, and normal BMD after adjusting for covariates (p = .004). There is a high prevalence of low BMD in Caucasian women with SLE, and this status was associated with higher damage accrual scores, supporting that disease damage may itself be a major contributor to the low BMD. Women with SLE with organ damage require regular bone status monitoring to prevent further musculoskeletal damage.
Diabetes mellitus is a serious chronic disease in which the oxidant-antioxidant balance is impaired, causing many complications, including hepatopathy. In this study, the effects of short-term and low-dose N-acetylcysteine (NAC) administration on the biochemical, proinflammatory, and oxidative stress parameters in the liver tissue of diabetic rats were investigated. Twenty-four adult male Wistar albino rats weighing approximately 250-300 g were divided into 4 groups (n = 6): Control, Streptozotosin (STZ)-induced diabetes (DM), NAC treatment (60 mg/kg), and STZ-induced diabetes treated with NAC (DM+NAC; 60 mg/kg). NAC treatment was administered intraperitoneally as a single daily dose for 7 days. At the end of the experiment (3 weeks), blood and liver samples were collected for biochemical parameter analysis. Lipid peroxidation, antioxidant parameters, and nitric oxide (NOx) levels were determined by spectrophotometric method. Tissue inflammation parameters were evaluated by ELISA. Lipid peroxidation, proinflammatory cytokines, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values increased significantly with diabetes. NAC treatment significantly decreased serum ALT and AST levels and proinflammatory cytokines in the diabetic group. Liver glutathione (GSH) and NOx levels increased significantly in the DM+NAC group (p < 0.05). While NAC treatment reduced lipid peroxidation in the liver, it improved the inflammatory response and antioxidant status. The beneficial effect of NAC treatment may be due to its antioxidant activity and the resulting increased level of GSH. The results show that low-dose and short-term NAC treatment had a positive effect on oxidative damage and inflammation in liver tissue. NAC can be used as a potential antioxidant in diabetes to prevent hepatopathy.
Aims: This critical review aimed to summarize: (1) the variability and determinants of testosterone (T) measurements; and (2) reference values for the variability and determinants of T measurements in children.
Background: As T is a representative androgen, it has been widely used to explain male vulnerability to child health and developmental problems. T measurements in children, however, have been challenging because of low levels, diurnal and episodic secretion patterns, limited quantity and quality of the samples, and inconsistent study findings.
Methods: The search strategy used PubMed, CINAHL, Cochrane Library, Embase, Scopus, and Google Scholar. Studies published between 2008 through 2020 that examined factors influencing T measurement were included. The final 30 studies were selected using two appraisal forms. We extracted five categories of data from the reports.
Findings: Variability and determinants of T measurement included assay methods, the source of samples, and child demographic and environmental characteristics. T levels were higher 1-3 months after birth and in males up to 1 year; fewer sex differences were found up to 10-12 years. Serum T levels measured by using liquid chromatography-mass spectrometry were most reliable because immunoassays overestimated the levels, especially in neonates. T levels were stable at different temperatures and durations of storage, although sample collection remained an ongoing challenge for researchers.
Conclusion: Depending on the study aims and feasibility, mass-spectrometry, multi-methods, and multi-materials are the recent trends in T measurement. Immunoassays may be an option if the study aims for relative rather than absolute comparisons.
Osteoarthritis (OA) is the most prevalent cause of chronic pain and disability in people aged ≥45 years, with the knee being the most affected joint. Neurotrophic factors like brain-derived neurotrophic factor (BDNF), which promotes neurogenesis and neuroplasticity, have been shown to significantly affect chronic pain. This study aimed to investigate the relationship between resting plasma BDNF levels and clinical pain and quantitative sensory testing measures in older adults with knee OA pain. For this secondary analysis, a previously reported dataset was used comprised of older adults with knee OA who underwent quantitative sensory testing. A comprehensive generalized linear model (GLM) was built to understand the relationships between BDNF and important covariates, followed by the elastic net (EN) method for variable selection. GLM was then performed to regress BDNF levels against only the variables selected by EN. The mean age of the sample was 60.4 years (SD = 9.1). Approximately half of the participants were female (53%). Plasma BDNF levels were positively associated with heat pain threshold and the numeric rating scale of pain. Future mechanistic studies are needed to replicate and extend these findings to advance our knowledge of the underlying mechanisms of BDNF in knee OA and other chronic pain conditions.