Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Novel aptamer-based technologies can identify >7000 analytes per sample, offering a high-throughput alternative to traditional immunoassays in biomarker discovery. However, the specificity for distinct proteins has not been thoroughly studied in the context of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:We assessed the use of SOMAscan, an aptamer-based technology, for the quantification of eight immune activation biomarkers and cystatin C among 498 African American Study of Kidney Disease and Hypertension (AASK) participants using immunoassays as the gold standard. We evaluated correlations of serum proteins as measured by SOMAscan versus immunoassays with each other and with iothalamate-measured GFR. We then compared associations between proteins measurement with risks of incident kidney failure and all-cause mortality. RESULTS:both methods. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOMAscan counterparts. CONCLUSIONS:SOMAscan is an efficient and relatively reliable technique for quantifying IL-8, TNFRSF1B, cystatin C, and TNFRSF1A in CKD and detecting their potential associations with clinical outcomes.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_23_CJN11700921.mp3.

Few studies have examined whether maternal caregiving representations are associated with maternal reflective functioning (MRF), especially when MRF is evaluated longitudinally beginning in pregnancy. This study addresses this gap by evaluating whether prenatal and postnatal MRF are associated with mothers' caregiving representations assessed at 7 months postpartum, and by exploring theoretically unexpected MRF scores in each of the representational categories. Forty-seven mothers were recruited during their last trimester of pregnancy from an obstetrics clinic at a university hospital located in a large mid-western city in the United States. During pregnancy, mothers completed the Pregnancy Interview, and at 7 months postpartum they completed the Parent Development Interview (PDI) and the Working Model of the Child Interview. Results indicate that higher prenatal and postnatal MRF increased the odds of being classified as balanced versus disengaged. At 7 months, MRF also increased the odds of being balanced vs. distorted. Ten mothers who were classified as balanced or distorted had unexpected prenatal MRF scores, and six mothers had unexpected MRF scores when representations were assessed concurrently. Mothers classified as balanced with low MRF scores tended to have a low level of education, whereas mothers classified as distorted with high MRF scores had responses that were hostile, helpless, and role-reversed.

Background/UNASSIGNED:Although the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment. Objective/UNASSIGNED:To evaluate the association between Decipher genomic classifier scores and biopsy Gleason upgrading among patients on active surveillance. Design setting and participants/UNASSIGNED:This was a retrospective cohort study among patients with low- and favorable intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of their clinical care. Outcome measurements and statistical analysis/UNASSIGNED:We evaluated the association between the Decipher score and any increase in biopsy Gleason grade group (GG) using univariable and multivariable logistic regression. We compared the area under the receiver operating characteristic curve (AUC) for models comprising baseline clinical variables with or without the Decipher score. Results and limitations/UNASSIGNED:= 0.02). The Decipher score was associated with upgrading among patients with biopsy GG 1 disease, but not GG2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51-0.74) was improved by integration of the Decipher score (AUC 0.69, 95% CI 0.58-0.80). Conclusions/UNASSIGNED:The Decipher genomic classifier score was associated with short-term biopsy Gleason upgrading among patients on active surveillance. Patient summary/UNASSIGNED:The results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores.

The use of planned oocyte cryopreservation for nonmedical need has been steadily increasing, especially since the experimental label on this procedure was lifted nearly 10 years ago. With this rise, patients' desires to postpone or conserve their reproductive potential have become increasingly nuanced, and the need for complex individualized counseling has grown. In addition, there are several ethical considerations, including risks, access, and patient comprehension that must be discussed with patients who are considering this procedure. In this review, we provide an in-depth discussion of these concepts, highlighting the need for individualized and comprehensive counseling that recognizes the gaps in knowledge that remains in this somewhat novel domain.

INTRODUCTION:Optimism is associated with better cardiovascular health, yet little is known about the underlying mechanisms and whether protective relationships are consistently observed across diverse groups. This study examines optimism's association with lipid profiles over time and separately among Black and White men and women. METHODS:Data were from 3,206 middle-aged adults in the Coronary Artery Risk Development in Young Adults study. Optimism was measured in 2000-2001 using the Revised Life Orientation Test. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol measurements were obtained at 5-year intervals through 2015-2016. Linear mixed models evaluated relationships between optimism and lipids, adjusting for covariates, including prebaseline lipids. Subgroup differences were examined using interaction terms and stratification. All analyses were conducted in 2020. RESULTS:Higher optimism was associated with both lower baseline total cholesterol (β= -2.33, 95% CI= -4.31, -0.36) and low-density lipoprotein cholesterol levels (β= -1.93, 95% CI= -3.65, -0.21) and a more rapid incremental increase in both markers over time (total cholesterol: β=0.09, 95% CI=0.00, 0.18; low-density lipoprotein cholesterol: β=0.09, 95% CI=0.01, 0.16). No associations were apparent with baseline triglycerides, high-density lipoprotein cholesterol, or changes in either lipid over time. Tests for interaction only found evidence of heterogeneous associations with baseline triglyceride levels, but stratified models hinted at stronger protective associations with baseline levels of total cholesterol and low-density lipoprotein cholesterol among White women. CONCLUSIONS:Optimism may help diverse individuals establish healthy total cholesterol and low-density lipoprotein cholesterol levels before midlife. Although associations were largely consistent across subgroups, stronger associations among White men and White women highlight a need to study optimism's health impact in diverse samples.

BACKGROUND:Recent literature suggests that the gap in prevalence of binge drinking between men and women is closing, but little is known about sex-specific differences in trends and correlates of binge drinking among older Americans. METHODS:A total of 18,794 adults, aged 65 years and older were surveyed in the 2015-2019 National Survey on Drug Use and Health. We estimated trends in prevalence of past-month binge drinking (≥5 drinks on the same occasion for men and ≥4 drinks for women), stratified by sex. Correlates of binge drinking were estimated for men and women separately, focusing on demographic characteristics, chronic diseases, past-month tobacco and cannabis use, depression, and emergency department use. Multivariable generalized linear models using Poisson and log link were used to examine associations stratified by sex. RESULTS:Binge drinking among older men increased from 12.8% in 2015 to 15.7% in 2019 (p = 0.02) but remained stable among older women (7.6% to 7.3%, p = 0.97). In adjusted models, having a college degree was associated with higher risk of binge drinking among women (adjusted prevalence ratio [aPR] = 1.68, 95% CI: 1.13-2.50), but lower risk among men (aPR = 0.69, 95% CI: 0.56-0.85). Men who are separated or divorced were also at higher risk (aPR = 1.25, 95% CI: 1.05-1.50), but women were not. Both men and women reporting past-month use of tobacco (men aPR = 1.87, 95% CI: 1.61-2.17, women aPR = 2.11, 95% CI: 1.71-2.60) and cannabis (men aPR = 2.05, 95% CI: 1.63-2.58, women aPR = 2.77, 95% CI 2.00-3.85) were at higher risk of binge drinking. CONCLUSIONS:Binge drinking has increased among older men whereas it has remained stable among older women in the United States. Interventions should consider that although tobacco and cannabis use is associated with an increased risk of binge drinking among both older men and women, demographic correlates tend to differ by sex.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Ketamine is efficacious in treating treatment-resistant depression in medical settings and the drug was approved for such use by the US Federal Drug Administration in 2019. However, little is known about how use outside of medical settings relates to depression. We determined whether recreational ketamine use, relative to the use of other drugs, is related to the current experience of depression among adolescents. METHODS:We examined data from the 2016 to 2019 Monitoring the Future nationally representative survey of high school seniors in the United States (N = 15,673). We determined how past-year drug use and frequency of past-year drug use were associated with students reporting a high level of current depressive symptoms relative to other students. RESULTS:Ketamine use was associated with highest risk for a high level of depression (aPR = 1.55, 95% confidence interval [CI]: 1.24-1.94), followed by use of cannabis (aPR = 1.29, 95% CI: 1.19-1.39), and nonmedical use of tranquilizers (aPR = 1.22, 95% CI: 1.04-1.44) and amphetamine (aPR = 1.17, 95% CI: 1.01-1.34). Alcohol use was associated with decreased risk (aPR = 0.92, 95% CI: 0.85-0.99). With respect to frequency of past-year use, more frequent use of ketamine and cannabis was associated with increased risk for a high level of depression in a dose-response-like manner, with past-year use of ketamine and cannabis ≥10 times associated with increased risk for depression by 70% and 40%, respectively. DISCUSSION AND CONCLUSIONS/CONCLUSIONS:Past-year recreational ketamine use is a risk factor for reporting current depression than most other drugs. SCIENTIFIC SIGNIFICANCE/CONCLUSIONS:This was the first study to compare the risk of use of various drugs in relation to depression.

SCOPE:Lack of biomarkers is a challenge for the accurate assessment of protein intake and interpretation of observational study data. The study aims to identify biomarkers of a protein-rich dietary pattern. METHODS AND RESULTS:The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart) trial is a randomized cross-over feeding study which tested three dietary patterns with varied macronutrient content (carbohydrate-rich; protein-rich with about half from plant sources; and unsaturated fat-rich). In 156 adults, differences in log-transformed plasma metabolite levels at the end of the protein- and carbohydrate-rich diet periods using paired t-tests is examined. Partial least-squares discriminant analysis is used to identify a set of metabolites which are influential in discriminating between the protein-rich versus carbohydrate-rich dietary patterns. Of 839 known metabolites, 102 metabolites differ significantly between the protein-rich and the carbohydrate-rich dietary patterns after Bonferroni correction, the majority of which are lipids (n = 35), amino acids (n = 27), and xenobiotics (n = 24). Metabolites which are the most influential in discriminating between the protein-rich and the carbohydrate-rich dietary patterns represent plant protein intake, food or beverage intake, and preparation methods. CONCLUSIONS:The study identifies many plasma metabolites associated with the protein-rich dietary pattern. If replicated, these metabolites may be used to assess level of adherence to a similar dietary pattern.

BACKGROUND:Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied. METHODS:In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43-55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31-50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples. RESULTS:The median for the sum of urine inorganic and methylated As species (ΣAs) (μg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (μg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched. CONCLUSIONS:While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels.