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Abstract Background The coevolution of male traits and female mate preferences has led to the elaboration and diversification of sexually selected traits; however the mechanisms that mediate trait-preference coevolution are largely unknown. Carotenoid acquisition and accumulation are key determinants of the expression of male sexually selected carotenoid-based coloration and a primary mechanism maintaining the honest information content of these signals. Carotenoids also influence female health and reproduction in ways that may alter the costs and benefits of mate choice behaviours and thus provide a potential biochemical link between the expression of male traits and female preferences. To test this hypothesis, we manipulated the dietary carotenoid levels of captive female house finches (Carpodacus mexicanus) and assessed their mate choice behavior in response to color-manipulated male finches. Results Females preferred to associate with red males, but carotenoid supplementation did not influence the direction or strength of this preference. Females receiving a low-carotenoid diet were less responsive to males in general, and discrimination among the colorful males was positively linked to female plasma carotenoid levels at the beginning of the study when the diet of all birds was carotenoid-limited. Conclusions Although female preference for red males was not influenced by carotenoid intake, changes in mating responsiveness and discrimination linked to female carotenoid status may alter how this preference is translated into choice. The reddest males, with the most carotenoid rich plumage, tend to pair early in the breeding season. If carotenoid-related variations in female choice behaviour shift the timing of pairing, then they have the potential to promote assortative mating by carotenoid status and drive the evolution of carotenoid-based male plumage coloration.

Importance: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited., Objective: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4)., Design, Setting, and Participants: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024., Exposure: Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022., Main Outcomes and Measures: Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response., Results: A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were -0.03 (95% CI, -0.07 to 0.00) for arsenic, -0.05 (95% CI, -0.09 to -0.004) for cobalt, -0.05 (95% CI, -0.07 to -0.02) for copper, -0.04 (95% CI, -0.08 to -0.001) for uranium, and -0.03 (95% CI, -0.06 to -0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was -0.30 (95% CI, -0.47 to -0.14) for APOE4 carriers and -0.10 (95% CI, -0.19 to -0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status., Conclusions and Relevance: In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals' metal exposure levels and genetic profiles.

Background: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants. Exposure to VOCs is associated with cardiovascular disease risk factors, including elevated blood pressure in susceptible populations. However, research in the general population, particularly among nonsmoking adults, is limited. We hypothesized that higher VOC exposure is associated with higher blood pressure and hypertension, among nonsmokers., Methods: We included 4 cycles of data (2011-2018) of nonsmoking adults (n=4430) from the National Health and Nutrition Examination Survey. Urinary VOC metabolites were measured by ultraperformance liquid chromatography-mass spectrometry, adjusted for urine dilution, and log-transformed. We estimated mean differences in blood pressure using linear models and prevalence ratio of stage 2 hypertension using modified Poisson models with robust standard errors. Models were adjusted for age, sex, race and ethnicity, education, body mass index, estimated glomerular filtration rate, and National Health and Nutrition Examination Survey cycle., Results: Participants were 54% female, with a median age of 48 years, 32.3% had hypertension, and 7.9% had diabetes. The mean differences (95% CI) in systolic blood pressure were 1.61 (0.07-3.15) and 2.46 (1.01-3.92) mm Hg when comparing the highest with the lowest quartile of urinary acrolein (N-acetyl-S-[2-carboxyethyl]-L-cysteine) and 1,3-butadiene (N-acetyl-S-[3,4-dihydroxybutyl]-L-cysteine) metabolites. The prevalence ratios for hypertension were 1.06 (95% CI, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) when comparing the highest with lowest quartiles of urinary acrolein (N-acetyl-S-[2-carboxyethyl]-L-cysteine) and 1,3-butadiene (N-acetyl-S-[3,4-dihydroxybutyl]-L-cysteine), respectively., Conclusions: Exposure to VOCs may be a relevant yet understudied environmental contributor to cardiovascular disease risk in the nonsmoking, US population.

Background: Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression., Objectives: The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis)., Methods: We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors., Results: At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors., Conclusions: Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression., Competing Interests: Funding Support and Author Disclosures The Multi-Ethnic Study of Atherosclerosis (MESA) is supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute; and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the U.S. Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. Work in the authors’ laboratories is also supported in part by NIH grants P42ES023716, P42ES010349, P42ES033719, P30ES009089, T32ES007322, R01ES029967, R01HL155576, R01ES029967, and R01ES028758. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Congenital heart patients undergoing congenital heart surgery in the first year of life are at high risk of having a neurodevelopmental disorder. The most common difficulties are related to executive functioning. The following questions were assessed in the current project: Are patients having congenital heart surgery after one year of life at lower risk for neurodevelopmental disorders? At what age do executive function deficits manifest?, Methods: We evaluated executive function in four groups of congenital heart patients who had undergone congenital heart surgery. These groups were high-risk patients with and without a genetic syndrome associated with a neurodevelopmental disorder and low-risk patients with and without a genetic syndrome associated with a neurodevelopmental disorder. We evaluated executive function using the Behavior Rating Inventory of Executive Function - Preschool Version, Behavior Rating Inventory of Executive Function-2, and Minnesota Executive Function Scale at various ages. We compared the rates of executive function deficits in the high- and low-risk groups as well as compared that to the published norms for age. We also assessed at what age these deficits become apparent., Conclusion: We found that both high- and low-risk groups had higher levels of executive functioning deficits compared to the norms for age. The low-risk group's degree of executive function deficits appeared a little lower than the high-risk group. However, it was difficult to comment on the statistical significance. We also saw that executive function deficits often do not become apparent for many years after surgery. This finding highlights the need for continued evaluation of functioning as these kids mature.

Background: Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (the Multi-Ethnic Study of Atherosclerosis)., Methods: We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as a mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net., Results: During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the hazard ratios (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted hazard ratios (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality., Conclusions: This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health., Competing Interests: None.

Background: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy that presents with a triad of hemolytic anemia, thrombocytopenia, and acute kidney impairment. It can be attributed to mutations in an array of different complement proteins leading to the overactivation of the complement system, the most impacted being the alternative pathway. Though rare, influenza B has been documented as a potential trigger to the development of aHUS., Case Presentation: We discuss a 10-year-old girl with a history of aHUS who was found to have a repeat episode of aHUS following an influenza B infection. There have only been a few reports of aHUS triggered by influenza B, making this a unique case. Given the recurrence and atypical features present in this case, a genetic workup was obtained, which showed a heterozygous mutation of complement protein CD46. The presence of mutations in CD46 is a known predisposing factor to aHUS, but influenza B infection is rarely implicated as a trigger to aHUS. The prognosis of aHUS varies and is dependent on the complement mutation specific to the individual., Conclusion: Patients with CD46 mutations have been shown to have high rates of relapse but less long-term kidney damage, as seen in this case. Clinicians should be aware of the association between influenza B and aHUS to improve patient outcomes., Competing Interests: Conflicts of Interest: The authors declare they have no conflicts of interest., (© 2024 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Background: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants. Exposure to VOCs is associated with cardiovascular disease (CVD) risk factors, including elevated blood pressure (BP) in susceptible populations. However, research in the general population, particularly among non-smoking adults, is limited. We hypothesized that higher VOC exposure is associated with higher BP and hypertension, among non-smokers., Methods: We included four cycles of data (2011-2018) of non-smoking adults (n=4,430) from the National Health and Nutrition Examination Survey (NHANES). Urinary VOC metabolites were measured by ultra-performance liquid chromatography-mass spectrometry, adjusted for urine dilution, and log-transformed. We estimated mean differences in BP using linear models and prevalence ratio of stage 2 hypertension using modified Poisson models with robust standard errors. Models were adjusted for age, sex, race and ethnicity, education, body mass index, estimated glomerular filtration rate and NHANES cycle., Results: Participants were 54% female, with a median age of 48 years, 32.3% had hypertension, and 7.9% had diabetes. The mean differences (95% CI) in systolic BP were 1.61 (0.07, 3.15) and 2.46 (1.01, 3.92) mmHg when comparing the highest to lowest quartile of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA) metabolites. The prevalence ratios (PR) for hypertension were 1.06 (1.02, 1.09) and 1.05 (1.01, 1.09) when comparing the highest to lowest quartiles of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA), respectively., Conclusions: Exposure to VOCs may be relevant yet understudied environmental contributors to CVD risk in the non-smoking, US population., Competing Interests: DISCLOSURES The authors have no conflicts of interest to disclose.

Industrial disasters have caused hazardous air pollution and public health impacts. Response officials have developed limited exposure guidelines to direct them during the event; often, guidelines are outdated and may not represent relevant elevated-exposure periods. The 2019 Intercontinental Terminals Company (ITC) fire in Houston, Texas led to large-scale releases of benzene and presented a public health threat. This incident highlights the need for effective response and nimble, rapid public health communication. We developed a data-driven visualization tool to store, display, and interpret ambient benzene concentrations to assist health officials during environmental emergencies. Guidance values to interpret risk from acute exposure to benzene were updated using recent literature that also considers exposure periodicity. The visualization platform can process data from different sampling instruments and air monitors automatically, and displays information publicly in real time, along with the associated risk information and action recommendations. The protocol was validated by applying it retrospectively to the ITC event. The new guidance values are 6-30 times lower than those derived by the Texas regulatory agency. Fixed-site monitoring data, assessed using the protocol and revised thresholds, indicated that eight shelter-in-place and 17 air-quality alerts may have been considered. At least one of these shelter-in-place alerts corresponded to prolonged, elevated benzene concentrations (~1000 ppb). This new tool addresses essential gaps in the timely communication of air pollution measurements, provides context to understand potential health risks from exposure to benzene, and provides a clear protocol for local officials in responding to industrial air releases of benzene. Integr Environ Assess Manag 2024;20:533-546. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Background: Marijuana is the third most used drug in the world., Objectives: Because the cannabis plant is a known scavenger of metals, we hypothesized that individuals who use marijuana will have higher metal biomarker levels compared with those who do not use., Methods: We combined data from the National Health and Nutrition Examination Survey (2005-2018) for n = 7,254 participants, classified by use: non-marijuana/non-tobacco, exclusive marijuana, exclusive tobacco, and dual marijuana and tobacco use. Five metals were measured in blood and 16 in urine using inductively coupled plasma mass spectrometry; urinary metals were adjusted for urinary creatinine., Results: Participants reporting exclusive marijuana use compared with non-marijuana/non-tobacco use had statistically significantly higher mean cadmium levels in blood [ 1.22 μ g / L (95% CI: 1.11, 1.34); p < 0.001 ] and urine [ 1.18 μ g / g (95% CI: 1.0, 1.31); p = 0.004 ] and statistically significantly higher mean lead levels in blood [ 1.27 μ g / dL (95% CI: 1.07, 1.50); p = 0.006 ] and urine [ 1.21 μ g / g (95% CI: - 0.006 , 1.50); p = 0.058 ]., Discussion: Our results suggest marijuana is a source of cadmium and lead exposure. Research regarding cannabis use and cannabis contaminants, particularly metals, should be conducted to address public health concerns related to the growing number of cannabis users. https://doi.org/10.1289/EHP12074.

Background: The prevalence of hypertension is higher among Black adults than among White and Hispanic adults. Nevertheless, reasons underlying the higher rates of hypertension in the Black population remain unclear but may relate to exposure to environmental chemicals such as volatile organic compounds (VOCs)., Methods: We evaluated the associations of blood pressure (BP) and hypertension with VOC exposure in non-smokers and smokers in a subgroup of the Jackson Heart Study (JHS), consisting of 778 never smokers and 416 age- and sex-matched current smokers. We measured urinary metabolites of 17 VOCs by mass spectrometry., Results: After adjusting for covariates, we found that amoong non-smokers, metabolites of acrolein and crotonaldehyde were associated with a 1.6 mm Hg (95%CI: 0.4, 2.7; p = 0.007) and a 0.8 mm Hg (95%CI: 0.01, 1.6; p = 0.049) higher systolic BP, and the styrene metabolite was associated with a 0.4 mm Hg (95%CI: 0.09, 0.8, p = 0.02) higher diastolic BP. Current smokers had 2.8 mm Hg (95% CI 0.5, 5.1) higher systolic BP. They were at higher risk of hypertension (relative risk = 1.2; 95% CI, 1.1, 1.4), and had higher urinary levels of several VOC metabolites. Individuals who smoke had higher levels of the urinary metabolites of acrolein, 1,3-butadiene, and crotonaldehyde and were associated with higher systolic BP. The associations were stronger among participants who were <60 years of age and male. Using Bayesian kernel machine regression to assess the effects of multiple VOC exposures, we found that the relationship between VOCs and hypertension among non-smokers was driven primarily by acrolein and styrene in non-smokers, and crotonaldehyde in smokers., Conclusions: Hypertension in Black individuals may be attributed, in part, to VOC exposure from the environment or tobacco smoke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Volatile organic compounds (VOCs) are airborne toxicants abundant in outdoor and indoor air. High levels of VOCs are also present at various Superfund and other hazardous waste sites; however, little is known about the cardiovascular effects of VOCs. We hypothesized that ambient exposure to VOCs exacerbate cardiovascular disease (CVD) risk by depleting circulating angiogenic cells (CACs)., Approach and Results: In this cross-sectional study, we recruited 603 participants with low-to-high CVD risk and measured 15 subpopulations of CACs by flow cytometry and 16 urinary metabolites of 12 VOCs by LC/MS/MS. Associations between CAC and VOC metabolite levels were examined using generalized linear models in the total sample, and separately in non-smokers. In single pollutant models, metabolites of ethylbenzene/styrene and xylene, were negatively associated with CAC levels in both the total sample, and in non-smokers. The metabolite of acrylonitrile was negatively associated with CD45 dim /CD146 + /CD34 + /AC133 + cells and CD45 + /CD146 + /AC133 + , and the toluene metabolite with AC133 + cells. In analysis of non-smokers (n = 375), multipollutant models showed a negative association with metabolites of ethylbenzene/styrene, benzene, and xylene with CD45 dim /CD146 + /CD34 + cells, independent of other VOC metabolite levels. Cumulative VOC risk score showed a strong negative association with CD45 dim /CD146 + /CD34 + cells, suggesting that total VOC exposure has a cumulative effect on pro-angiogenic cells. We found a non-linear relationship for benzene, which showed an increase in CAC levels at low, but depletion at higher levels of exposure. Sex and race, hypertension, and diabetes significantly modified VOC associated CAC depletion., Conclusion: Low-level ambient exposure to VOCs is associated with CAC depletion, which could compromise endothelial repair and angiogenesis, and exacerbate CVD risk., (Copyright © 2022. Published by Elsevier Inc.)

Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Exposure to air pollution, specifically particulate matter of diameter ≤2.5 μm (PM 2.5 ), is a well-established risk factor for CVD. However, the contribution of gaseous pollutant exposure to CVD risk is less clear., Objective: To examine the vascular effects of exposure to individual volatile organic compounds (VOCs) and mixtures of VOCs., Methods: We measured urinary metabolites of acrolein (CEMA and 3HPMA), 1,3-butadiene (DHBMA and MHBMA3), and crotonaldehyde (HPMMA) in 346 nonsmokers with varying levels of CVD risk. On the day of enrollment, we measured blood pressure (BP), reactive hyperemia index (RHI - a measure of endothelial function), and urinary levels of catecholamines and their metabolites. We used generalized linear models for evaluating the association between individual VOC metabolites and BP, RHI, and catecholamines, and we used Bayesian Kernel Machine Regression (BKMR) to assess exposure to VOC metabolite mixtures and BP., Results: We found that the levels of 3HPMA were positively associated with systolic BP (0.98 mmHg per interquartile range (IQR) of 3HPMA; CI: 0.06, 1.91; P = 0.04). Stratified analysis revealed an increased association with systolic BP in Black participants despite lower levels of urinary 3HPMA. This association was independent of PM 2.5 exposure and BP medications. BKMR analysis confirmed that 3HPMA was the major metabolite associated with higher BP in the presence of other metabolites. We also found that 3HPMA and DHBMA were associated with decreased endothelial function. For each IQR of 3HPMA or DHBMA, there was a -4.4% (CI: -7.2, -0.0; P = 0.03) and a -3.9% (CI: -9.4, -0.0; P = 0.04) difference in RHI, respectively. Although in the entire cohort the levels of several urinary VOC metabolites were weakly associated with urinary catecholamines and their metabolites, in Black participants, DHBMA levels showed strong associations with urinary norepinephrine and normetanephrine levels., Discussion: Exposure to acrolein and 1,3-butadiene is associated with endothelial dysfunction and may contribute to elevated risk of hypertension in participants with increased sympathetic tone, particularly in Black individuals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Age-related deficits in associative processing are well-documented (e.g., Naveh-Benjamin, 2000) and have been assumed to be the result of a general deficit that affects all types of binding. However, recent behavioral research has indicated that the visual configuration of the information that is presented to older adults influences the degree to which this binding deficit is exhibited by older adults (Overman, Dennis et al, 2019; Overman, Dennis, et al., 2018). The purpose of the present study was to further clarify the neural underpinnings of the associative deficit in aging and to examine whether functional activity at encoding differs with respect to the visual configuration and the type of associative being encoded. Using both univariate and multi-voxel pattern analysis, we found differences in both the magnitude of activation and pattern of neural responses associated with the type of association encoded (item-item and item-context). Specifically, our results suggest that, when controlling for stimuli composition, patterns of activation in sensory and frontal regions within the associative encoding network are able to distinguish between different types of associations. With respect to the MTL, multivariate results suggest that only patterns of activation in the PrC in older, but not younger adults, can distinguish between associations types. These findings extend prior work regarding the neural basis of associative memory in young and older adults, and extends the predictions of the binding of item and context model (BIC; Diana, Yonelinas, Ranganath, 2007) to older adults., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background Context: Transforaminal lumbar interbody fusion (TLIF) and dual-approach anteroposterior (AP) are common techniques to achieve circumferential fusion for lumbar spondylolisthesis. It is unclear which approach is more cost-effective., Purpose: Our goal was to determine the incremental cost-effectiveness ratio (ICER) by calculating the cost per quality-adjusted life year (QALY) for each approach., Study Design/setting: This study is a propensity-matched cost-effectiveness comparison., Patient Sample: Patients with lumbar spondylolisthesis undergoing single-level AP fusion or TLIF and enrolled in a prospective observational surgical database were included in this study., Outcome Measures: The outcome measures in this study were the Oswestry Disability Index (ODI) and the Short Form-6D (SF-6D)., Methods: From a prospective surgical database, patients with lumbar spondylolisthesis undergoing single-level AP fusion were propensity matched to a TLIF cohort based on age, gender, body mass index, smoking status, workers compensation, preoperative ODI, and back and leg pain numeric scores. Quality-adjusted life years gained were determined using baseline and 1- and 2-yearpostoperative SF-6D scores. Cost was calculated from actual, direct hospital costs and included subsequent postsurgical costs (epidural spinal injections, spine-related emergency department visits, readmissions, and revision surgery)., Results: Thirty-one cases of AP fusions were identified and propensity matched to 31 TLIF patients. Patients undergoing TLIF had a shorter mean operative time (270 vs. 328 minutes, p=.039) but no difference in estimated blood loss (526 vs. 548 cc, p=.804) or hospital length of stay (4.5 vs. 6.1 days, p=.146). Quality-adjusted life years gained at 2 years were also similar (0.140 vs. 0.130, p=.672). The mean index surgery and the total 2-year costs were lower for TLIF compared with AP (index: $29,428 vs. $31,466; final: $30,684 vs. $331,880). As overall costs were lower and QALYs gained were similar for TLIF compared with AP fusion, TLIF was the dominant intervention with an ICER of $116,327., Conclusions: Under our study parameters, surgical treatment of lumbar spondylolisthesis with TLIF is more cost-effective compared with AP fusion. Because of the short-term follow-up, the longevity of this should be further investigated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVEThe goal of this study was to determine efficacy and cost-effectiveness of Cell Saver in 2- and 3-level lumbar decompression and fusion.METHODSPatients seen at a tertiary care spine center who were undergoing a posterior 2- or 3-level lumbar decompression and fusion were randomized to have Cell Saver used during their surgery (CS group, n = 48) or not used (No Cell Saver [NCS] group, n = 47). Data regarding preoperative and postoperative hemoglobin and hematocrit, estimated blood loss, volume of Cell Saver blood reinfused, number of units and volume of allogeneic blood transfused intraoperatively and postoperatively, complications, and costs were collected. Costs associated with Cell Saver use were calculated based on units of allogeneic blood transfusions averted.RESULTSDemographics and surgical parameters were similar in both groups. The mean estimated blood loss was similar in both groups: 612 ml in the CS group and 742 ml in the NCS group. There were 53 U of allogeneic blood transfused in 29 patients in the NCS group at a total blood product cost of $67,688; and 38 U of allogeneic blood transfused in 16 patients in the CS group at a total blood cost of $113,162, resulting in a cost of $3031 per allogeneic blood transfusion averted using Cell Saver.CONCLUSIONSCell Saver use produced lower rates of allogeneic transfusion but was found to be more expensive than using only allogeneic blood for 2- and 3-level lumbar degenerative fusions. This increased cost may be reasonable to patients who perceive that the risks associated with allogeneic transfusions are unacceptable.■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized controlled trial; evidence: class III.

Background: Anterior cervical discectomy and fusion (ACDF) for cervical degenerative disease is an accepted treatment for symptomatic cervical radiculopathy and myelopathy. One- and two-level fusions are much more common and more widely studied. Outcomes and revision rates for three- and four-level ACDF have not been well described. The purpose of this study is to report on clinical outcomes and revision rates following multilevel ACDF., Methods: Patients who underwent three- or four-level anterior cervical discectomy with plate fixation between 2006 and 2011 from a single-center multi-surgeon practice for symptomatic cervical degenerative disease were identified. Improvements in neck disability index (NDI), neck and arm pain scores two years after surgery and revision rates were analyzed., Results: Forty-six patients with a mean age of 55.9 years were included in the analysis. Twenty-one (46%) were male, 10 (22%) were smokers. Forty-one (89%) underwent three-level fusion and 5 (11%) underwent four-level fusion. NDI improved from 34.46 at baseline to 25.47 at 2 years. Neck pain improved from 7.04 at baseline to 3.95 and arm pain improved from 6.24 to 3.09 at 2 year follow up. Sixteen patients (35%) returned to surgery within 2 years with 11 of these patients (24%) returning for non-union. The average number of days to revision surgery was 750.6±570.3 days., Conclusions: Patients undergoing three- and four-level ACDF for multilevel cervical disease demonstrate substantial improvement in outcomes. However, the two-year revision rate is relatively high at 35% with the majority of these patients returning due to non-union., Competing Interests: Conflicts of Interest: Dr. JL Laratta reports consulting for Evolution Spine and research support from Orthopaedic Science Research Foundation and Norton Healthcare. Dr. LY Carreon reports consulting for AO Spine, trips/travel for Center for Spine Surgery and Research of the University of Southern Denmark and University of Louisville Institutional Review Board, and research support from the Scoliosis Research Society, Orthopedic Educational Research Fund, Integra and Pfizer. Dr. R. Kirk Owens reports consulting for Medtronic, Nuvasive and Alphatec, trips/travel from Depuy Synthes, Medtronic, and Nuvasive, research support from Pfizer and Integra, and fellowship support from Norton Healthcare. The other authors have no conflicts of interest to declare.

OBJECTIVE Patient-reported outcomes (PROs) such as the Oswestry Disability Index (ODI) and EuroQol-5D (EQ-5D) are widely used to evaluate treatment outcomes following spine surgery for degenerative conditions. The goal of this study was to use the Charlson Comorbidity Index (CCMI) as a measure of general health status, for comparison with standard PROs. METHODS The authors examined serial CCMI scores, complications, and PROs in 371 patients treated surgically for degenerative lumbar spine conditions who were enrolled in the Quality and Outcomes Database from a single center. The cohort included 152 males (41%) with a mean age of 58.7 years. Patients with no, minor, or major complications were compared at baseline and at 1 year postoperatively. RESULTS Minor complications were observed in 177 patients (48%), and major complications in 34 (9%). There were no significant differences in preoperative ODI, EQ-5D, or CCMI among the 3 groups. At 1 year, there was a significantly greater deterioration in CCMI in the major complication group (1.03) compared with the minor (0.66) and no complication groups (0.44, p < 0.006), but no significant difference in ODI or EQ-5D. CONCLUSIONS Despite equivalent improvements in PROs, patients with major complications actually had greater deterioration in their general health status, as evidenced by worse CCMI scores. Because CCMI is predictive of medical and surgical risk, patients who sustained a major complication now carry a greater likelihood of adverse outcomes with future interventions, including subsequent spine surgery. Although PRO scores are a key metric, they fail to adequately reflect the potential long-term impact of major perioperative complications.

Background Context: Obesity is a growing problem in health care. Studies have demonstrated similar functional outcomes but higher complication rates after spine surgery in obese patients., Purpose: This study aimed to compare patient-reported outcomes and revision rates 5 years after instrumented posterior lumbar fusion between normal, overweight, and obese patients., Study Design: Propensity matched case control., Patient Sample: Patients who had posterior instrumented lumbar spinal fusion from 2001 to 2008 from a single spine specialty center with complete preoperative and 5-year postoperative outcome measures were identified., Outcome Measures: Oswestry Disability Index (ODI), Back Pain (0-10) and Leg Pain (0-10) Numeric Rating Scales, and Short Form-36 Physical Composite Summary Scores (SF-36 PCS)., Methods: Three comparison groups, one with body mass index (BMI) ≥20-25 kg/m 2 (normal), another with ≥25-<30 kg/m 2 (overweight), and another with ≥30-40 kg/m 2 (obese) were created using propensity matching techniques based on demographics, baseline clinical outcome measures, and surgical characteristics. Five-year postoperative outcome measures and revision rates in the three groups were compared. One-way analysis of variance was used to compare continuous variables, and Fisher exact test was used to compare categorical variables between the groups. Significance was set at p<.01., Results: There were 82 cases matched in each cohort. Estimated blood loss (440 cc vs. 702 cc vs. 798 cc, p=.000) and operative time (234 minutes vs. 263 minutes vs. 275 minutes, p=.003) were significantly greater in the overweight and obese patients. Improvements in ODI (14.2 vs. 9.6 vs. 10.4, p=.226), SF-36 PCS (5.9 vs. 2.9 vs. 3.5, p=.361), back pain (3.0 vs. 2.0 vs. 2.1, p=.028), and leg pain (3.0 vs. 2.3 vs. 2.3, p=.311) scores were similar among the groups. Revision rates (14 vs. 15 vs. 13, p=.917), and time between index and revision surgery (p=.990) were similar among the three groups as well., Conclusion: When considering a subset of patient-reported outcomes and revision surgery after 5 years, patients with an elevated BMI >25 at baseline did not appear to have worse outcomes than those with a normal BMI of 20-25 when undergoing posterior lumbar fusion surgery. Obesity should not be considered a contraindication to surgery in patients with appropriate surgical indications., (Copyright © 2016 Elsevier Inc. All rights reserved.)

OBJECTIVE Studies have shown that anxious or depressed patients may have poorer outcomes after lumbar fusion. These conclusions were drawn from questionnaires specifically designed to measure anxiety and depression. The objective of this study is to determine if responses to the EQ-5D anxiety/depression domain or the items used to calculate the 36-Item Short-Form Health Survey (SF-36) Mental Component Summary (MCS) can predict outcomes after lumbar fusion surgery. METHODS Patients enrolled in the National Neurosurgery Quality and Outcomes Database from a single center with 1-year follow-up were identified. The outcomes collected include the Oswestry Disability Index (ODI), EQ-5D, SF-36, and the back- and leg-pain numeric rating scales (range 0-10). Linear regression modeling was performed to predict the 1-year ODI scores using the EQ-5D anxiety/depression domain and the 14 items used to calculate SF-36 MCS. RESULTS Complete data were available for 312 (88%) of 353 eligible patients. The mean patient age was 58.5 years, 175 (56%) patients were women, and 52 patients were smokers. After controlling for other factors, the item in the SF-36 that asks "Have you felt downhearted and depressed?" is the strongest predictor of the 1-year ODI score (r(2) = 0.191; p = 0.000) and 1-year EQ-5D score (r(2) = 0.205; p = 0.000). Neither the EQ-5D anxiety/depression domain nor the diagnoses of anxiety or depression were predictors of 1-year outcomes. CONCLUSIONS Patient responses to SF-36 item "Have you felt downhearted and depressed?" account for 20% of the variability of the 1-year ODI and EQ-5D scores and can be used by clinicians to screen for anxiety or depression in patients prior to lumbar fusion surgery. Clinicians may offer psychological support to these patients preoperatively in order to improve treatment outcomes.