Exercise: Just What the Doctor Ordered, But Why? Elucidating Mechanisms for Women's Increased High-Density Lipoprotein Benefit From Exercise and for the Health ABC Study.

High-density lipoprotein (HDL) is protective against cardiovascular disease. Exercise can increase HDL concentration, and some evidence suggests that this effect occurs more strongly in women than in men. Both HDL and exercise are associated with inflammation. We hypothesized a sex-by-exercise interaction on HDL level, whereby women would benefit from exercise more strongly than men, and tumor necrosis factor alpha and serum soluble tumor necrosis factor receptor-2 would mediate this relationship. This study included 2,957 older adult participants (1,520 women; 41% Black, 59% White; 73.6-years-old) from the Health, Aging, and Body Composition study. Regression models revealed a positive exercise-HDL relationship in women only (sex-by-exercise interaction: ß = 0.09, p = .013; exercise on HDL in women: ß = 0.07, p = .015), mediated by TNFα (axb = 0.15; CI: 0.01, 0.30), suggesting that exercise may increase HDL levels in women through reduced inflammation. Given that vascular risk contributes to Alzheimer's disease risk, findings have implications for sex differences in AD risk factors.

Effects of Perceived Discrimination on Behavioral Health Outcomes in People Aging With Traumatic Brain Injury.

OBJECTIVE: To evaluate major and everyday experiences of discrimination (MED and EED, respectively) in relation to behavioral health outcomes in people with traumatic brain injury (PwTBI). SETTING: Outpatient research laboratory. PARTICIPANTS: Adults, 50 years or older, with a chronic (1+ year) history of moderate or severe TBI ( N = 118). DESIGN: Cross-sectional observational study. MAIN MEASURES: MED and EED (primary measures of interest) and behavioral health outcomes: global cognition, psychological symptoms, neurobehavioral symptoms, societal participation, and health-related quality of life (HRQoL). In participants with available geodata ( N = 28), neighborhood socioeconomic deprivation (ND) was examined as a potential contributor to MED, EED, and measured outcomes. RESULTS: EED and MED were significantly associated with psychological symptoms, neurobehavioral symptoms, and HRQoL after correction for multiple comparisons. Counter to expectations, EED were related to higher societal participation. MED and EED were unrelated to cognition. When MED and EED were entered together in hierarchical regressions, only EED made significant contributions beyond demographic and injury-related covariates to each outcome. Sensitivity analyses revealed that most of these relationships were not solely accounted for by disability-related discrimination. ND showed negligible associations with discrimination but moderate effect sizes for cognition and participation. Race was not significantly related to discrimination and was not a significant predictor in regression models but was strongly associated with ND. CONCLUSION: The current data provide preliminary support for perceived discrimination as an important factor in neurobehavioral and psychosocial health, but not cognitive performance, after TBI. These relationships appear to be driven by daily experiences of discriminatory treatment versus single major instances of injustice. Measured outcomes may also reflect socioeconomic challenges and structural discrimination faced by diverse PwTBI, although more work in this area is urgently needed. Multiple sources of marginalization and disenfranchisement and their functional effects should be considered in TBI rehabilitation and outcome monitoring.

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial.

BACKGROUND: Catheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation. METHODS AND FINDINGS: We investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children's Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = -1.138, 95% CI = -2.062, -0.214, p = 0.002) and superior mFPC (MD = -0.999, 95% CI = -1.961, -0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = -0.342, 95% CI = -0.680, -0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = -0.092, 95% CI = -0.680, -0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers. CONCLUSIONS: We observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02703090.

The neuroinflammatory marker sTNFR2 relates to worse cognition and tau in women across the Alzheimer's disease spectrum.

Introduction: Despite women showing greater Alzheimer's disease (AD) prevalence, tau burden, and immune/neuroinflammatory response, whether neuroinflammation impacts cognition differently in women versus men and the biological basis of this impact remain unknown. We examined sex differences in how cerebrospinal fluid (CSF) neuroinflammation relates to cognition across the aging-mild cognitive impairment (MCI)-AD continuum and the mediating role of phosphorylated tau (p-tau) versus other AD biomarkers. Methods: Participants included 284 individuals from the Alzheimer's Disease Neuroimaging Initiative study. CSF neuroinflammatory markers included interleukin-6, tumor necrosis factor α, soluble tumor necrosis factor receptor 2 (sTNFR2), and chitinase-3-like protein 1. AD biomarkers were CSF p-tau181 and amyloid beta1-42 levels and magnetic resonance imaging measures of hippocampal and white matter hyperintensity volumes. Results: We found a sex-by-sTNFR2 interaction on Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Higher levels of sTNFR2 related to poorer cognition in women only. Among biomarkers, only p-tau181 eliminated the female-specific relationships between neuroinflammation and cognition. Discussion: Women may be more susceptible than men to the adverse effects of sTNFR2 on cognition with a potential etiological link with tau to these effects.

The Characterization of Postoperative Mechanical Respiratory Requirement in Neonates and Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass in a Single Tertiary Institution.

OBJECTIVES: Although neonates and infants undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at high risk of developing perioperative morbidity and mortality, including lung injury, the intraoperative profile of lung injury in this cohort is not well-described. Given that the postoperative course of patients in the pediatric cardiac surgical arena has become increasingly expedited, the objective of this study was to characterize the profiles of postoperative mechanical ventilatory support in neonates and infants undergoing cardiac surgery on CPB and to examine the characteristics of lung mechanics and lung injury in this patient population who are potentially amendable to early postoperative recovery in a single tertiary pediatric institution. DESIGN: A retrospective data analysis of neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. SETTING: A single-center, university teaching hospital. PARTICIPANTS: The study included 328 neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. INTERVENTIONS: A subset of 128 patients were studied: 58 patients undergoing ventricular septal defect (VSD) repair, 36 patients undergoing complete atrioventricular canal (CAVC) repair, and 34 patients undergoing bidirectional Glenn (BDG) shunt surgery. MEASUREMENTS AND MAIN RESULTS: Of the entire cohort, 3.7% experienced in-hospital mortality. Among all surgical procedures, VSD repair (17.7%) was the most common, followed by CAVC repair (11.0%) and BDG shunt surgery (10.4%). Of patients who underwent VSD repair, CAVC repair, and BDG shunt surgery, 65.5%, 41.7%, and 67.6% were off mechanical ventilatory support within 24 hours postoperatively, respectively. In all three of the surgical repairs, lung compliance decreased after CPB compared to pre-CPB phase. Sixty point three percent of patients with VSD repair and 77.8% of patients with CAVC repair showed a PaO2/FIO2 (P/F) ratio of <300 after CPB. Post- CPB P/F ratios of 120 for VSD patients and 100 for CAVC patients were considered as optimal cutoff values to highly predict prolonged (>24 hours) postoperative mechanical ventilatory support. A higher volume of transfused platelets also was associated with postoperative ventilatory support ≥24 hours in patients undergoing VSD repair, CAVC repair, and BDG shunt surgery. CONCLUSIONS: There was a high incidence of lung injury after CPB in neonates and infants, even in surgeries amendable for early recovery. Given that CPB-related factors (CPB duration, crossclamp time) and volume of transfused platelet were significantly associated with prolonged postoperative ventilatory support, the underlying cause of cardiac surgery-related lung injury can be multi-factorial.

The Evaluation of a Noninvasive Respiratory Volume Monitor in Mechanically Ventilated Neonates and Infants.

BACKGROUND: The respiratory volume monitor (RVM) (ExSpiron, Respiratory Motion Inc, Watertown, MA) uses thoracic impedance technology to noninvasively and continuously measure tidal volume (TV), respiratory rate (RR), and minute ventilation (MV). We aimed to validate the accuracy of the RVM to assess ventilation in neonates and infants by comparing it to spirometry. METHODS: We used the RVM and Respironics NM3 spirometer (Respironics NM3 Respiratory Profile Monitor, Philips Healthcare, Amsterdam, the Netherlands) to record simultaneous and continuous measurements of MV, TV, and RR. The RVM measurements, with and without external calibration, were compared to the Respironics NM3 spirometer using Bland-Altman analysis. The relative errors (Bland-Altman) between RVM and Respironics NM3 were calculated and used to compute individual patient bias, precision, and accuracy as the mean error, the standard deviation (SD) of the error, and the root mean square error. Bland-Altman limits of agreement (LoA) were computed, and equivalence tests were performed. RESULTS: Forty patients were studied to compare the RVM and Respironics NM3 measurements. The mean difference (ie, bias) for MV was 1.8% with 95% LoA, defined as mean ± 1.96 SD, in the range of -12.1% to 15.7%. Similarly, the mean difference (ie, bias) for TV and RR was 1.2% (95% LoA, -11.0% to 13.5%) and 0.6% (95% LoA, -3.7% to 5.0%), respectively. The mean measurement precision of the RVM relative to the Respironics NM3 for MV, TV, and RR was 10.8%, 8.9%, and 8.4%, respectively. The mean measurement accuracy for MV, TV, and RR across patients was 11.0%, 9.7%, and 7.1%, respectively. CONCLUSIONS: The data demonstrate that the RVM measures TV and MV in this cohort with an average relative error of 11% when using patient calibration and 16.9% without patient calibration. The average relative error of RR was 7.1%. The RVM provides accurate measurement of RR, TV, and MV in mechanically ventilated neonates and infants.

Cognitive Reserve in Individuals Aging With Traumatic Brain Injury: Independent and Interactive Effects on Cognitive Functioning.

OBJECTIVE: To examine the influence of 2 temporal factors-age and injury chronicity-on the relationship between cognitive reserve (CR) and cognitive functioning in older adults with chronic traumatic brain injury (TBI). SETTING: Outpatient research laboratory. PARTICIPANTS: Adults, 50 years or older, with a 1- to 45-year history of moderate or severe TBI (N = 108). DESIGN: Cross-sectional observational study. MAIN MEASURES: CR was estimated using demographically corrected performance on a word-reading test (an approximation of premorbid IQ). Injury chronicity was operationalized as number of years since the date of injury. Composite cognitive scores were computed from performances on neuropsychological tests of processing speed, executive functioning, and memory. RESULTS: CR was positively and significantly related to all cognitive performances independent of age, injury chronicity, and injury severity. Greater injury chronicity significantly attenuated the effect of CR on processing speed such that individuals more distal from their injury date evidenced a weaker positive relationship between CR and performance. CONCLUSION: Temporal factors may modify associations between CR and cognition. Findings suggest that the protective effects of CR are temporally delimited, potentially contending with declines in brain reserve. The prognostic value of traditional outcome determinants should be considered in the context of injury chronicity.

Perceived discrimination and blood pressure in individuals aging with traumatic brain injury.

Purpose/Objective: Older adults with a history of traumatic brain injury (TBI) remain an understudied population, resulting in a paucity of geriatric-specific guidelines. Given an increased vascular risk among older adults with TBI, we aimed to examine distal predictors of vascular health in this population. Specifically, we sought to compare levels of perceived discrimination in Black and White older adults with a history of complicated mild, moderate, or severe TBI, and to examine the relationship between levels of discrimination and pulse pressure, a measure of vascular health. Research Method/Design: Self-report measures of everyday discrimination (ED) and major experiences of discrimination (MED) were completed by 106 individuals aging with TBI (27 identified as Black, 79 identified as White). Resting blood pressure was collected during the assessment. Results: MED, but not ED, was significantly higher among Black individuals versus White individuals aging with TBI. Greater MED was significantly associated with higher pulse pressure independent of race and antihypertensive medication status. There was a marginally significant race by MED interaction, where the association between MED and pulse pressure was observed in Black individuals but not White individuals. Injury severity was not associated with pulse pressure, nor were there significant severity by discrimination interactions on pulse pressure. Conclusions/Implications: Discrimination, which may arise from multiple sources of bias (e.g., related to race, disability), is associated with vascular burden. These findings suggest that patients' experiences of discrimination should be addressed as a factor that contributes to health and well-being in brain injury rehabilitation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment.

BACKGROUND: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined. OBJECTIVE: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). METHODS: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1-42 (Aß42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. RESULTS: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aß42 (B = -1.01, p = 0.02); greater inflammation was associated with higher levels of Aß42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s < 0.05). CONCLUSION: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.

Race and ethnicity considerations in traumatic brain injury research: Incidence, reporting, and outcome.

PRIMARY OBJECTIVE: This study has three goals: to determine whether there is a higher rate of traumatic brain injury (TBI) for people of color (POC), whether TBI studies report racial/ethnic demographics, and whether there is a discrepancy in discharge destinations between Whites and POC. We examined whether 1) a higher percentage of POC would sustain head injuries than expected, 2) the majority of TBI studies examined (>50%) would not include racial/ethnic demographics, and 3) Whites would be discharged to further treatment over POC. RESEARCH DESIGN: Retrospective study and literature review. METHODS AND PROCEDURES: Data from the Pennsylvania Trauma System Foundation was used to determine the number of POC with TBI using X2 analysis, as well as where patients with TBI were being discharged using a configural frequency analysis. PubMed was used for the literature search to examine the frequency of reporting race/ethnicity in TBI literature. MAIN OUTCOMES AND RESULTS: Results demonstrated that Blacks sustain more TBIs than would be expected (p < .05), the majority of scientific studies (78%) do not report racial/ethnic demographic information, and Whites are discharged to further care more often than POC. CONCLUSIONS: These findings highlight differences in incidence and treatment of TBI between White individuals and POC, raising important considerations for providers and researchers.

Traumatic brain injury and frontal lobe plasticity.

Over 1.4 million people in the United States experience traumatic brain injury (TBI) each year and approximately 52,000 people die annually due to complications related to TBI. Traditionally, TBI has been viewed as a static injury with significant consequences for frontal lobe functioning that plateaus after some window of recovery, remaining relatively stable thereafter. However, over the past decade there has been growing consensus that the consequences of TBI are dynamic, with unique characteristics expressed at the individual level and over the life span. This chapter first discusses the pathophysiology of TBI in order to understand its dynamic process and then describes the behavioral changes that are the result of injury with focus on frontal lobe functions. It integrates a historical perspective on structural and functional brain-imaging approaches used to understand how TBI impacts the frontal lobes, as well as more recent approaches to examine large-scale network changes after TBI. The factors most useful for outcome prediction are surveyed, along with how the theoretical frameworks used to predict recovery have developed over time. In this chapter, the authors argue for the need to understand outcome after TBI as a dynamic process with individual trajectories, taking a network theory perspective to understand the consequences of disrupting frontal systems in TBI. Within this framework, understanding frontal lobe dysfunction within a larger coordinated neural network to study TBI may provide a novel perspective in outcome prediction and in developing individualized treatments.

Enhanced default mode connectivity predicts metacognitive accuracy in traumatic brain injury.

OBJECTIVE: To examine the role that intrinsic functional networks, specifically the default mode network, have on metacognitive accuracy for individuals with moderate to severe traumatic brain injury (TBI). METHOD: A sample of 44 individuals (TBI, n = 21; healthy controls [HCs], n = 23) were included in the study. All participants underwent an MRI scan and completed neuropsychological testing. Metacognitive accuracy was defined as participants' ability to correctly judge their item-by-item performance on an abstract reasoning task. Metacognitive values were calculated using the signal detection theory approach of area under the receiver operating characteristic curve. Large-scale subnetworks were created using Power's 264 Functional Atlas. The graph theory metric of network strength was calculated for six subsystem networks to measure functional connectivity. RESULTS: There were significant interactions between head injury status (TBI or HC) and internetwork connectivity between the anterior default mode network (DMN) and salience network on metacognitive accuracy (R2 = 0.13, p = .047) and between the posterior DMN and salience network on metacognitive accuracy (R2 = 0.15, p = .038). There was an interpretable interaction between head injury status and internetwork connectivity between the attention network and salience network on metacognitive accuracy (R2 = 0.13, p = .067). In all interactions, higher connectivity predicted better metacognitive accuracy in the TBI group, but this relationship was reversed for the HC group. CONCLUSION: Enhanced connectivity to both anterior and posterior regions within the DMN facilitates metacognitive accuracy postinjury. These findings are integrated into a larger literature examining network plasticity in TBI. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Validation of a Second-Generation Near-Infrared Spectroscopy Monitor in Children With Congenital Heart Disease.

BACKGROUND: Cerebral oximetry using near-infrared spectroscopy is a noninvasive optical technology to detect cerebral hypoxia-ischemia and develop interventions to prevent and ameliorate hypoxic brain injury. Cerebral oximeters are calibrated and validated by comparison of the near-infrared spectroscopy-measured cerebral O2 saturation (SctO2) to a "field" or reference O2 saturation (REF CX) calculated as a weighted average from arterial and jugular bulb oxygen saturations. In this study, we calibrated and validated the second-generation, 5 wavelength, FORE-SIGHT Elite with the medium sensor (source-detector separation 12 and 40 mm) for measurement of SctO2 in children with congenital heart disease. METHODS: After institutional review board approval and written informed consent, 63 children older than 1 month and ≥2.5 kg scheduled for cardiac catheterization were enrolled. Self-adhesive FORE-SIGHT Elite medium sensors were placed on the right and left sides of the forehead. Blood samples for calculation of REF CX were drawn simultaneously from the aorta or femoral artery and the jugular bulb before (T1) and shortly after (T2) baseline hemodynamic measurements. FORE-SIGHT Elite SctO2 measurements were compared to the REF CX (REF CX = [0.3 SaO2] + [0.7 SjbO2]) using Deming regression, least squares linear regression, and Bland-Altman analysis. RESULTS: Sixty-one subjects (4.5 [standard deviation 4.4] years of age; 17 [standard deviation 13] kg, male 56%) completed the study protocol. Arterial oxygen saturation ranged from 64.7% to 99.1% (median 96.0%), jugular bulb venous oxygen saturation from 34.1% to 88.1% (median 68.2%), the REF CX from 43.8% to 91.4% (median 76.9%), and the SctO2 from 47.8% to 90.8% (median 76.3%). There was a high degree of correlation in SctO2 between the right and left sensors at a given time point (within subject between sensor correlation r = 0.91 and 95% confidence interval [CI], 0.85-0.94) or between T1 and T2 for the right and left sensors (replicates, within subject between time point correlation r = 0.95 and 95% CI, 0.92-0.96). By Deming regression, the estimated slope was 0.966 (95% CI, 0.786-1.147; P = .706 for testing against null hypothesis of slope = 1) with a y intercept of 2.776 (95% CI, -11.102 to 16.654; P = .689). The concordance correlation coefficient was 0.873 (95% CI, 0.798-0.922). Bland-Altman analysis for agreement between SctO2 and REF CX that accounted for repeated measures (both in times and sensors) found a bias of -0.30% (95% limits of agreement: -10.56% to 9.95%). CONCLUSIONS: This study calibrated and validated the FORE-SIGHT Elite tissue oximeter to accurately measure SctO2 in pediatric patients with the medium sensor.

Volatile Anesthetic Attenuates Phagocyte Function and Worsens Bacterial Loads in Wounds.

BACKGROUND: Previously we have shown that volatile anesthetic isoflurane attenuated neutrophil recruitment and phagocytosis in mouse sepsis and skin inflammation models. The objectives of this study were to test ex vivo function of neutrophils in patients who underwent cardiac catheterization under volatile anesthesia versus intravenous anesthesia (IA), and also to assess the effect of anesthesia on surgical site infections (SSIs) using mouse model to understand the clinical relevance of anesthesia-induced immunomodulation. METHODS: Whole blood from patients who underwent cardiac catheterization procedures either by volatile anesthesia or IA was collected and subjected to phagocytosis assay and a lipopolysaccharide-induced tumor necrosis factor-α assay. Mouse SSI with Staphylococcus aureus USA300 was created, and the effect of isoflurane and propofol exposure (short or long exposure) on bacterial loads was tested. RESULTS: Neutrophil phagocytosis was significantly attenuated after the induction of volatile anesthesia in patients, but not by IA. Monocyte phagocytosis was not affected by the anesthesia regimen. Bacterial loads following SSIs were significantly higher in mice receiving long, but not short, isoflurane exposure. Propofol exposure did not affect bacterial loads. DISCUSSION: Neutrophil phagocytosis can be affected by the type of anesthesia, and preclinical model of SSIs showed potential clinical relevance. The effects of anesthesia regimen on SSIs in patients needs to be studied extensively in the future.

Correction: The evolution of cost-efficiency in neural networks during recovery from traumatic brain injury.

[This corrects the article DOI: 10.1371/journal.pone.0170541.].

Diminished neural network dynamics after moderate and severe traumatic brain injury.

Over the past decade there has been increasing enthusiasm in the cognitive neurosciences around using network science to understand the system-level changes associated with brain disorders. A growing literature has used whole-brain fMRI analysis to examine changes in the brain's subnetworks following traumatic brain injury (TBI). Much of network modeling in this literature has focused on static network mapping, which provides a window into gross inter-nodal relationships, but is insensitive to more subtle fluctuations in network dynamics, which may be an important predictor of neural network plasticity. In this study, we examine the dynamic connectivity with focus on state-level connectivity (state) and evaluate the reliability of dynamic network states over the course of two runs of intermittent task and resting data. The goal was to examine the dynamic properties of neural networks engaged periodically with task stimulation in order to determine: 1) the reliability of inter-nodal and network-level characteristics over time and 2) the transitions between distinct network states after traumatic brain injury. To do so, we enrolled 23 individuals with moderate and severe TBI at least 1-year post injury and 19 age- and education-matched healthy adults using functional MRI methods, dynamic connectivity modeling, and graph theory. The results reveal several distinct network "states" that were reliably evident when comparing runs; the overall frequency of dynamic network states are highly reproducible (r-values>0.8) for both samples. Analysis of movement between states resulted in fewer state transitions in the TBI sample and, in a few cases, brain injury resulted in the appearance of states not exhibited by the healthy control (HC) sample. Overall, the findings presented here demonstrate the reliability of observable dynamic mental states during periods of on-task performance and support emerging evidence that brain injury may result in diminished network dynamics.

Prefrontal gray matter volume predicts metacognitive accuracy following traumatic brain injury.

OBJECTIVE: To examine metacognitive ability (MC) following moderate to severe traumatic brain injury (TBI) using an empirical assessment approach and to determine the relationship between alterations in gray matter volume (GMV) and MC. METHOD: A sample of 62 individuals (TBI n = 34; healthy control [HC] n = 28) were included in the study. Neuroimaging and neuropsychological data were collected for all participants during the same visit. MC was quantified using an approach borrowed from signal detection theory (Type II area under the receiver operating characteristic curve calculation) to evaluate judgments during a modified version of the 3rd edition of the Wechsler Adult Intelligence Scale's Matrix Reasoning subtest where half of the items were presented randomly and half were presented in the order of increasing difficulty. Retrospective confidence judgments were collected on an item-by-item basis. Brain volumetric analyses were conducted using FreeSurfer software. RESULTS: Analyses of the modified Matrix Reasoning task data demonstrated that HCs significantly outperformed TBIs (ordered: d = .63; random: d = .58). There was a significant difference between groups for MC for the randomly presented stimuli (d = .54) but not the ordered stimuli. There was an association between GMV and MC in the TBI group between the right orbital region and MC (R2 = .11). In the HC group, there were associations between the left posterior (R2 = .17), left orbital (R2 = .29), and left dorsolateral (R2 = .21) regions and MC. CONCLUSIONS: These results are consistent with those of previous research on MC in the cognitive neurosciences, but this study demonstrates that injury may moderate the regional contributions to MC. (PsycINFO Database Record

Diminished neural network dynamics in amnestic mild cognitive impairment.

Mild cognitive impairment (MCI) is widely regarded as an intermediate stage between typical aging and dementia, with nearly 50% of patients with amnestic MCI (aMCI) converting to Alzheimer's dementia (AD) within 30 months of follow-up (Fischer et al., 2007). The growing literature using resting-state functional magnetic resonance imaging reveals both increased and decreased connectivity in individuals with MCI and connectivity loss between the anterior and posterior components of the default mode network (DMN) throughout the course of the disease progression (Hillary et al., 2015; Sheline & Raichle, 2013; Tijms et al., 2013). In this paper, we use dynamic connectivity modeling and graph theory to identify unique brain "states," or temporal patterns of connectivity across distributed networks, to distinguish individuals with aMCI from healthy older adults (HOAs). We enrolled 44 individuals diagnosed with aMCI and 33 HOAs of comparable age and education. Our results indicated that individuals with aMCI spent significantly more time in one state in particular, whereas neural network analysis in the HOA sample revealed approximately equivalent representation across four distinct states. Among individuals with aMCI, spending a higher proportion of time in the dominant state relative to a state where participants exhibited high cost (a measure combining connectivity and distance), predicted better language performance and less perseveration. This is the first report to examine neural network dynamics in individuals with aMCI.

Inclusion of non-English-speaking patients in research: A single institution experience.

BACKGROUND: Considering the recent increase in medical care provided to patients from foreign countries and the diversity of languages spoken by families living within the United States, it is important to determine whether non-English-speaking patients have access to participate in clinical research from which they may benefit. AIMS: We aimed to determine the number of non-English-speaking patients presenting to Boston Children's Hospital for medical care between 2011 and 2016, the number of clinical research protocols active within the Department of Anesthesiology, Critical Care and Pain Medicine approved to enroll non-English-speaking patients, as well as the number of both non-English- and English-speaking patients approached and enrolled in these studies. Furthermore, we attempted to determine barriers that may have prevented non-English-speaking patients from inclusion in clinical research. METHODS: We conducted a retrospective review of various data sources during a 5-year period. Data included the number of non-English-speaking patients presenting to Boston Children's Hospital for care as well as the number of English- and non-English-speaking patients approached for studies at the Department of Anesthesiology each year. Additionally, we reviewed data from the IRB which included the justification that research teams provided when opting to exclude non-English-speaking participants. In addition, we attempted to determine the barriers that may have prevented these patients from inclusion in research protocols. RESULTS: We found that the number of non-English-speaking patients presenting to Boston Children's Hospital increased over time. However, the number of studies approved to enroll non-English-speaking patients within the Department of Anesthesiology and the rate of enrollment of these patients did not increase at the same rate. CONCLUSION: In order to increase the number of non-English-speaking patients approached to participate in research, we must improve cultural awareness and provide investigators with resources for interpreter and translation services.

Preoperative Thromboelastographic Profile of Patients with Congenital Heart Disease: Association of Hypercoagulability and Decreased Heparin Response.

OBJECTIVE: To describe the demographic and thromboelastographic characteristics of patients with congenital heart disease presenting with decreased heparin response before cardiac surgery. DESIGN: Retrospective, observational study. SETTING: Single institution, tertiary, academic, university hospital. PARTICIPANTS: The study comprised 496 pediatric and adult patients undergoing cardiac surgery for congenital heart disease. INTERVENTIONS: Retrospective review of medical records. MEASUREMENTS AND MAIN RESULTS: Data on preoperative thromboelastography (TEG), demographics, and response to heparin were collected retrospectively. Logistic regression analysis was used to study the association between TEG and response to heparin. Decreased heparin response (defined as activated clotting time <480 s initial bolus of 300 U/kg heparin) was observed in 23.6% of patients presenting for surgery. Age distribution and preoperative coagulation profiles were similar for both nonresponders and responders to heparin. Preoperatively, nonresponders demonstrated all thromboelastrographic characteristics consistent with a hypercoagulable profile (shorter reaction time, K value, wider angle, and maximum amplitude). Univariate logistic regression identified all TEG variables significantly associated with decreased heparin response. After adjustment for age, procedure type, and the presence of cyanosis, a multivariate logistic regression model identified the TEG variable K (≤1.3 min) as being significantly associated with decreased heparin response (odds ratio 3.7; confidence interval 2.3-5.8; p < 0.0001). CONCLUSIONS: Decreased response to heparin before cardiac surgery in patients with congenital heart disease is associated with preoperative hypercoagulability identified using a viscoelastic test. Additional studies are needed to better understand the etiology of decreased heparin response and potential clinical strategies to improve anticoagulation management.