Assessment of variability in the plasma 7k SomaScan proteomics assay.

SomaScan is a high-throughput, aptamer-based proteomics assay designed for the simultaneous measurement of thousands of proteins with a broad range of endogenous concentrations. In its most current version, the 7k SomaScan assay v4.1 is capable of measuring 7288 human proteins. In this work, we present an extensive technical assessment of this platform based on a study of 2050 samples across 22 plates. Included in the study design were inter-plate technical duplicates from 102 human subjects, which allowed us to characterize different normalization procedures, evaluate assay variability by multiple analytical approaches, present signal-over-background metrics, and discuss potential specificity issues. By providing detailed performance assessments on this wide range of technical aspects, we aim for this work to serve as a valuable resource for the growing community of SomaScan users.

Assessment of Triage DOA®, Status DS10, and DRIVEN-FLOW® M8-Z on-site drug screening kits for postmortem urine.

Based on the screening results of mass analyses using gas chromatography- mass spectrometry (GC-MS) and liquid chromatograph-tandem mass spectrometry (LC-MS/MS), we assessed the performance of Status DS10 (Status) and DRIVEN-FLOW® M8-Z (DF8), and compared the results with those of Triage DOA® (Triage) using 356 autopsy urine samples within one month of death. The sensitivity to benzodiazepines was 0.52 in Triage, 0.59 in Status, and 0.58 in DF8 with few false-positive cases. Triage detected triazolo-derivatives more easily than DF8. DF8 detected diazepam and nitro-benzodiazepines more easily than Status and Triage, with Status performing better than Triage. However, lorazepam detection with Status was difficult. There were 11 false-positive cases for amphetamines in Triage and 12 for Status-AMP at more than one week after death, but there were no false-positive in Status-MET and DF8. Tricyclic antidepressant (TCA) was detected in five cases by mass analysis, while there were 6 false-positive cases in Triage and 10 in both Status and DF8. In the TCA false-positive cases, tricyclic psychotics such as quetiapine, chlorpromazine, and carbamazepine existed. There were 23 true-positive and 6 false-positive cases for zolpidem in DF8 without false-negative cases. The accuracy of Status and DF8 for barbiturates or opiates was almost 1, but Triage was 0.98. There were no samples containing cocaine, THC, phencyclidine, or methadone. Based on the above, we conclude that Status and DF8 are comparable or slightly better than Triage, with fewer false-positive and fewer false-negative cases, except for TCA.

Dietary Pattern Trajectories in Middle Age and Physical Function in Older Age.

BACKGROUND: Increasingly, lifestyle factors in midlife are reported to impact health and functional status in old age. This work examines associations between dietary trajectories in middle age and subsequent impairments in physical function. METHOD: Data are from 851 participants (61% men, mean age at first dietary assessment = 47 years, range 30-59 years) from the Baltimore Longitudinal Study of Aging. We used latent class analysis to derive dietary trajectories based on adherence to the Alternative Healthy Eating Index-2010 (AHEI), and further classified them based on tertiles, as poor (score <39.3), intermediate (39.3-48.9), or good (>48.9). Physical function was assessed with the Short Physical Performance Battery (SPPB). Random effects tobit regression models were used to examine associations between dietary trajectories and later physical function. RESULTS: Two latent classes of AHEI scores were generated and labeled "greatly improved" or "moderately improved." In the greatly improved class, participants showed a trend in overall AHEI score from poor/intermediate to good diet categories across dietary assessments with age, over time. In the moderately improved class, the overall AHEI score shifted from poor to intermediate diet categories over time, and the prevalence of the good diet category remained low. Mean AHEI score between ages 30 and 59 years was higher in the greatly, than moderately, improved class. The moderately improved class had 1.6 points lower SPPB score (indicating poorer physical function) at older age than the greatly improved class (p = .022). CONCLUSIONS: Findings suggest that improving diet quality in middle age may contribute to better physical function in older age.

Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.

Importance: Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. Objective: To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. Design, Setting, and Participants: This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Exposures: Circulating TNF-α concentration. Main Outcomes and Measures: DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. Results: The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (ß [SE] = -0.01 [0.003]; P = 7.36 × 10-8), cg08122652 (ß [SE] = -0.008 [0.002]; P = 2.24 × 10-7), and cg22930808(ß [SE] = -0.01 [0.002]; P = 6.92 × 10-8); NLRC5 at cg16411857 (ß [SE] = -0.01 [0.002]; P = 2.14 × 10-13) and cg07839457 (ß [SE] = -0.02 [0.003]; P = 6.31 × 10-10); or ABO, at cg13683939 (ß [SE] = 0.04 [0.008]; P = 1.42 × 10-7) and cg24267699 (ß [SE] = -0.009 [0.002]; P = 1.67 × 10-7), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α-linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10-5; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10-5). Conclusions and Relevance: We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.

Brain response patterns to economic inequity predict present and future depression indices.

Widening economic inequity has been suggested to associate with depression. However, little is known about the underlying neural mechanisms of this link. Here, we demonstrate that functional magnetic resonance imaging activity patterns in the amygdala and hippocampus induced by the inequity between the self and other rewards during an economic game can predict participants' present and future (measured one year later) depression indices. Such predictions were not possible using participant's behavioural and socio-economic status measures. These findings suggest that sensitivity to economic inequity has a critical effect on human mood states, and the amygdala and hippocampus play a key role in individual differences in the effect.

[A Forensic Autopsy Case Applied for Asbestos-Related Disease].

We had a forensic autopsy case that required additive pathological examination for the asbestos-related lung disease compensatory application afterwards. A man in his sixties with a history of occupational asbestos inhalation who had neither visited a hospital nor received a physical examination received forensic autopsy because of his death from unknown cause. An inmate said, "He developed cough and dyspnea, and died in the progression of the symptoms." The autopsy revealed widespread pleural plaques on both sides of the parietal pleura and multiple tumors in both sides of the lungs. The cause of death was diagnosed as lung cancer. Additional pathological examination was asked by his family to certify that he had suffered from asbestos-related lung disease in order to apply to the Asbestos-related Damage Relief Law. The Japanese criteria of the compensation law of asbestos-related lung cancer is the detection of more than 5,000 asbestos bodies per gram of dry lung tissue, while his number of asbestos bodies was 4,860. Asbestos bodies were reported to be accumulated in the distal lung parenchyma with no pathological changes. The present lung samples were collected from proximal section around the tumor, which might have made the number of asbestos bodies less than the criteria. Both the number of patients suffering from asbestos-related lung disease and the number of forensic autopsy cases have increased in Japan. Collecting lung samples from the appropriate lung section is essential and should be noted when the lung cancer is suspected at forensic autopsy in order to apply for asbestos-related lung disease compensation.

Effects of a behavioral intervention that emphasizes spices and herbs on adherence to recommended sodium intake: results of the SPICE randomized clinical trial.

BACKGROUND: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. OBJECTIVE: We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. DESIGN: We conducted a 2-phase study that included adults ≥18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. RESULTS: Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: -956.8 mg/d; 95% CI: -1538.7, -374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: -1090 mg/d (P = 0.001); Joosens' equation mean difference: -796 mg/d (P = 0.04)]. CONCLUSIONS: A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159.

Genetic, physiological, and lifestyle predictors of mortality in the general population.

OBJECTIVES: We investigated the quality of 162 variables, focusing on the contribution of genetic markers, used solely or in combination with other characteristics, when predicting mortality. METHODS: In 5974 participants from the Rotterdam Study, followed for a median of 15.1 years, 7 groups of factors including age and gender, genetics, socioeconomics, lifestyle, physiological characteristics, prevalent diseases, and indicators of general health were related to all-cause mortality. Genetic variables were identified from 8 genome-wide association scans (n = 19,033) and literature review. RESULTS: We observed 3174 deaths during follow-up. The fully adjusted model (C-statistic for 15-year follow-up [C15y] = 0.80; 95% confidence interval [CI] = 0.79, 0.81) predicted mortality well [corrected]. Most of the additional information apart from age and sex stemmed from physiological markers, prevalent diseases, and general health. Socioeconomic factors and lifestyle contributed meaningfully to mortality risk prediction with longer prediction horizon. Although specific genetic factors were independently associated with mortality, jointly they contributed little to mortality prediction (C(15y) = 0.56; 95% CI = 0.55, 0.57). CONCLUSIONS: Mortality can be predicted reasonably well over a long period. Genetic factors independently predict mortality, but only modestly more than other risk indicators.