E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.

BACKGROUND: Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage. OBJECTIVE: We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype. METHODS: Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed. RESULTS: Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls. CONCLUSIONS: The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.

Epidemiology of Anterior and Lateral Basilar Skull Fractures With CSF Leak: A National Trauma Data Bank Analysis.

OBJECTIVE: Cerebrospinal fluid (CSF) leaks are a complication from dural violations that can occur in the setting of skull base fractures. No prior study provides a nationwide epidemiological analysis of traumatic CSF leaks. The objective of this report is to characterize patient demographics, injury-related variables, and operative management. METHODS: The national trauma data bank was queried for both anterior and lateral skull base fracture cases between 2008 and 2016. Clinical data were extracted. RESULTS: A total of 242 skull base fractures with CSF leak were identified. Most patients were male (84.3%), and the median patient age was 39.7±17.6 years old. Glasgow Coma Scale was 14.0 [interquartile range (IQR): 6.5-10.6] for lateral fractures, 13.0 (IQR: 3.0-10.0) for anterior fractures, and severe range for combined fractures at 7.0 (IQR: 5.0-9.0) (analysis of variance, P =0.122). Common mechanisms of injury were motor vehicle accidents (107, 44.2%), followed by falls and firearms (65, 26.9% and 20, 8.3%, respectively). The median length of stay was 2 weeks, with a median of 14 days (IQR: 10-25) for the anterior fractures and 10 days (IQR 5-19) among the lateral fractures ( P =0.592). Patients were most commonly discharged home in both the anterior (43.8%) and lateral (49.2%) groups. CONCLUSIONS: The prototypical patient tends to be a young adult male presenting with moderate-to-severe range neurological dysfunction after a vehicular accident. The overall prognosis of skull base fractures with CSF leak remains encouraging, with nearly half of these patients being discharged home within 2 weeks.

Restrictive eating across a spectrum from healthy to unhealthy: behavioral and neural mechanisms.

BACKGROUND: Restriction of food intake is a central feature of anorexia nervosa (AN) and other eating disorders, yet also occurs in the absence of psychopathology. The neural mechanisms of restrictive eating in health and disease are unclear. METHODS: This study examined behavioral and neural mechanisms associated with restrictive eating among individuals with and without eating disorders. Dietary restriction was examined in four groups of women (n = 110): healthy controls, dieting healthy controls, patients with subthreshold (non-low weight) AN, and patients with AN. A Food Choice Task was administered during fMRI scanning to examine neural activation associated with food choices, and a laboratory meal was conducted. RESULTS: Behavioral findings distinguished between healthy and ill participants. Healthy individuals, both dieting and non-dieting, chose significantly more high-fat foods than patients with AN or subthreshold AN. Among healthy individuals, choice was primarily influenced by tastiness, whereas, among both patient groups, healthiness played a larger role. Dorsal striatal activation associated with choice was most pronounced among individuals with AN and was significantly associated with selecting fewer high-fat choices in the task and lower caloric intake in the meal the following day. CONCLUSIONS: A continuous spectrum of behavior was suggested by the increasing amount of weight loss across groups. Yet, data from this Food Choice Task with fMRI suggest there is a behavioral distinction between illness and health, and that the neural mechanisms underlying food choice in AN are distinct. These behavioral and neural mechanisms of restrictive eating may be useful targets for treatment development.

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness.

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases.

Pure tone audiometry as assessed by a commercially-available mobile phone application compared to formal audiometry.

PURPOSE: Comparison of audiometric measurements of commercially available smartphone audiogram application thresholds as compared to gold standard audiometric evaluation. MATERIALS AND METHODS: A single-institution, original contribution. Ninety consecutive adult patients presenting to a tertiary care auditory clinic with auditory complaints were evaluated using standard audiometric testing and an application-based hearing test. Correlation between app results and standard audiogram for air conduction pure tone thresholds was evaluated. RESULTS: Mimi™ (Berlin, Germany) results for audiometric thresholds were moderately correlated with standard audiogram (r = 0.51-0.68) depending on severity. The percentage of patients whose hearing loss severity on formal audiometry results were accurately reflected in the Mimi™ (app-based hearing test: ABHT)1 results ranged from 18.2 to 80 %. Among patients whose results were at the extremes of hearing performance, app and standard audiogram results were similar. ABHT yielded an overall sensitivity of 35.5 % and specificity of 97.1 % for normal hearing, and an overall sensitivity of 80 % and specificity of 96 % for severe hearing loss. CONCLUSIONS: Results from an audiometric smart phone application showed accurate categorization of hearing loss at the high and extremes as compared to standard audiometry. However, correlation of pure tone values was more variable and dependent on hearing level.

Chronic difficulties are associated with poorer psychosocial functioning in the first year post-diagnosis in epithelial ovarian cancer patients.

OBJECTIVE: Ovarian cancer is characterized by poor prognosis, high levels of distress, disturbed sleep, and compromised quality of life (QOL). Although life stressors have been shown to significantly impact physical and psychological health in cancer populations, no studies have used a high-resolution stress assessment to differentiate effects of acute versus chronic stressors among women with ovarian cancer. We addressed this issue in the present prospective longitudinal study by examining how acute and chronic stress exposure in the year pre-diagnosis relate to depressive symptoms, sleep quality, and QOL over the first year post-diagnosis in women with ovarian cancer. METHODS: One hundred thirty-seven women completed the Life Events and Difficulties Schedule within a month of initial treatment for suspected ovarian cancer. Depressive symptoms, sleep, and QOL were measured pre-treatment, at six months, and one-year post-diagnosis. Mixed models were used to examine associations of acute and chronic stress pre-diagnosis with (a) change in psychosocial outcomes over the first year post-diagnosis and (b) levels of psychosocial outcomes across all time points. RESULTS: Both the number and severity of chronic difficulties (but not acute life events) were related to significantly greater depression, and poorer sleep quality and QOL, across all time-points. In contrast, these stress indices were unrelated to changes in psychosocial functioning over time. CONCLUSIONS: Chronic but not acute stress exposure predicted average levels of depression, sleep, and QOL in the first year post-diagnosis among women with ovarian cancer. Assessing stressors and designing interventions for reducing stress may thus be beneficial for ovarian cancer patients.

Initial Results from Mobile Low-Dose Computerized Tomographic Lung Cancer Screening Unit: Improved Outcomes for Underserved Populations.

INTRODUCTION: The National Lung Screening Trial (NLST) demonstrated that screening high-risk patients with low-dose computed tomography (CT) of the chest reduces lung cancer mortality compared with screening with chest x-ray. Uninsured and Medicaid patients usually lack access to this hospital-based screening test because of geographic and socioeconomic factors. We hypothesized that a mobile screening unit would improve access and confer the benefits demonstrated by the NLST to this underserved group, which is most at risk of lung cancer deaths. PATIENTS AND METHODS: We created a mobile unit by building a Samsung BodyTom portable 32-slice low-dose CT scanner into a 35-foot coach; it delivers high-quality images for both soft tissue and bone and includes a waiting area and high-speed wireless internet connection for fast image transfer. The unit was extensively tested to show robustness and stability of mobile equipment. This project was designed to screen uninsured and underinsured patients, otherwise with eligibility criteria identical to that of the National Lung Screening Trial, with the only difference being exclusion of patients eligible for Medicare (which provides financial coverage for CT-based lung cancer screening). RESULTS: We screened 550 patients (20% black, 3% Hispanic, 70% rural) with a male-to-female ratio of 1.1:1, median age 61 years (range, 55-64), and found 12 lung cancers at initial screen (2.2%), including 6 at stage I-II (58% of total lung cancers early stage) and 38 Lung-RADS 4 (highly suspicious) lesions that are being followed closely. Incidental findings included nonlung cancers and coronary artery disease. DISCUSSION: In this initial pilot study, using the first mobile low-dose whole body CT screening unit in the U.S., the initial cancer detection rate is comparable to that reported in the NLST, despite excluding patients over the age of 64 years who have Medicare coverage, but with marked improvement of screening rates specifically in underserved sociodemographic, racial, and ethnic groups and with better outcomes than conventionally found in the underserved and at lower cost per case. IMPLICATIONS FOR PRACTICE: This study shows clearly that a mobile low-dose CT scanning unit allows effective lung cancer screening for underserved populations, such as impoverished African Americans, Hispanics, Native Americans, or isolated rural groups, and has a pick-up rate of 1% for early stage disease. If confirmed in a planned randomized trial, this will be policy changing, as these groups usually present with advanced disease; this approach will produce better survival data at lower cost per case.

Habits are stronger with longer duration of illness and greater severity in anorexia nervosa.

OBJECTIVE: The aim of this study was to examine the relationship between habit strength and clinical features of anorexia nervosa (AN). Habit strength, separate from intention, relates to the persistence of behavior, and is measured by the Self-Report Habit Index (SRHI). We hypothesized that habit strength would be greater among individuals with AN than healthy controls (HC) and that habit strength would be associated with duration and severity of illness. METHOD: Participants were 116 women with AN (n = 69) and HC (n = 47) who completed the SRHI, the Eating Disorder Examination-Questionnaire (EDE-Q), and a multi-item laboratory meal. The SRHI assessed four domains and these subscales were averaged for the total score. RESULTS: Individuals with AN demonstrated significantly greater habit strength than HC in the total score (t114 = 7.00, p < .01), and within each domain (restrictive eating, compensatory behavior, delay of eating, and rituals). Total SRHI score was significantly associated with EDE-Q scores for both AN and HC groups (rAN = .59, pAN = <.001; rHC = .32, pHC = .030). Among patients, there was a significant association between SRHI and duration of illness (r = .38, p = .001). There was no significant association between SRHI and caloric intake (rAN = -.20, pAN = .10; rHC = -.25, pHC = .09). DISCUSSION: Habit strength was related to chronicity and severity of AN, suggesting that habit formation may play an important role in illness. These data suggest avenues for mechanism research and treatment development.

Inhibition of immunothrombosis does not affect pathogen capture and does not promote bacterial dissemination in a mouse model of sepsis.

After infection, neutrophils release neutrophil extracellular traps (NETs), decondensed DNA fibers decorated with both nuclear proteins and proteins derived from intracellular granules. These structures have a fundamental role in the development of immunothrombosis; a physiological process mediated by immune cells and molecules from the coagulation system that facilitates the recognition, containment, and destruction of pathogens. Although NETs and immunothrombi are widely hypothesized to be key host defense responses responsible for limiting bacterial dissemination, their actual role in this process has not been formally assessed within the context of a bloodstream infection. Mice were first treated with LPS to generate inflammation (NETs and immunothrombi) and then bacteria dissemination was analyzed by intravital microscopy and colony-forming units (CFU) assay. Blocking NETs or coagulation by the administration of DNase or Argatroban (thrombin inhibitor), respectively, did not modify the percentage of bacteria capture by Kupffer cells, neutrophils or platelets. Moreover, both inhibitors reduced the number of bacteria in the spleen, without modifying CFUs in the liver or lung. In conclusion, we demonstrate that immunothrombi are not necessary to limit the dissemination of bloodstream bacterial infections.

Leg Length Discrepancy: The Natural History (And What Do We Really Know).

BACKGROUND: The long-term effects of small limb length discrepancies have been poorly documented in the literature. References to low back pain, hip pathology, knee pathology, and foot problems abound in the popular literature. Health care providers frequently recommend the use of lifts for structural and functional limb length discrepancies, yet the natural history of limb length inequality as well as the effectiveness of treatments that may be recommended are obscure. The purpose of this paper is to document and evaluate the literature associated with small limb length discrepancies. METHODS: A search of the English literature was carried out using PubMed to identify papers dealing with the effects of limb length discrepancies. Papers reporting only expert opinion or case reports were excluded. RESULTS: Papers dealing with the natural history of limb length discrepancy as well as studies in which gait analysis was performed in patients with limb length discrepancy were identified. Only 10% of the population has exactly equal lower limb lengths. Approximately 90% of the population has a limb length discrepancy <1.0 cm. Hip and knee pathology is present in an increased number of patients with limb length discrepancies over 5 mm. Hip pathology is more often present in the long leg, knee pathology has been reported in various studies to be more common in either the long or short leg. Low back problems seem to be more common on the short side in patients with limb length discrepancies. A number of different compensatory mechanisms for limb length discrepancy have been identified during gait analysis. CONCLUSIONS: There seems to be a consensus that limb length discrepancies >2.0 cm are frequently a problem. There is some evidence that limb length discrepancies as little as 5 mm can lead to long-term pathology.

Benchmarking Psychosocial Skills Important for Talent Development.

How can high potential in childhood be transformed into outstanding adult accomplishment? Research indicates that individuals who become outstanding performers and producers have more than just raw talent in the domain or opportunities to develop their talent-they have the will, drive, and focus to take advantage of the opportunities with which they are presented, and the capacity to persist through failures even as the bar for success gets higher. Despite the importance of these psychosocial facilitators, they are among the least well understood in the field of gifted and talented research. In this study, we reviewed existing literature in order to build comprehensive list of the psychosocial variables associated with talent development across domains (visual art, dance, sports, academics, music, acting, medicine, and software engineering). With the help of psychologists with expertise in these domains, we completed an initial categorization of these skills and asked the experts to indicate at which of the three stages in talent development-the transition of abilities into competencies, competencies into expertise, and expertise to creative productivity or eminence-each psychosocial skill was important. We found promising general patterns of commonality as well as variation by domain and stage of talent development, and discuss the implications of this study on future research into psychosocial skill development.

Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer.

BACKGROUND: Patients with ovarian cancer often report elevated anxiety at diagnosis that decreases posttreatment. However, a minority of patients experience sustained anxiety. Few studies have examined risk factors for persistent anxiety or its physiologic sequelae in ovarian cancer. Therefore, the authors investigated associations between prior life events, anxiety, inflammation (plasma levels of interleukin-6), and diurnal cortisol profiles in patients with ovarian cancer during the first year postdiagnosis. METHODS: Participants (n = 337) completed surveys and had blood and salivary sampling prediagnosis, postchemotherapy (6 months), and 12 months after diagnosis. The Life Events and Difficulties Schedule was administered to a patient subset (n = 127) within 1 month of diagnosis. Linear mixed-effects models were used to analyze relations between anxiety and biologic variables over time. Linear regression models assessed whether anxiety trajectories mediated associations between prior stress exposure and biologic variables. Age, chemotherapy at 1 year, and cancer stage were covariates. RESULTS: Decreased anxiety was associated with a more normalized cortisol slope over time (ß = 0.092; P = .047). Early life adversity was related to flatter cortisol slopes over time (ß = -0.763; P = .002); this relation was partially mediated by anxiety trajectory (P = .046). More danger-related events prediagnosis were associated with sustained anxiety (ß = 0.537; P = .019) and flatter cortisol slopes over time (ß = -0.243; P = .047); anxiety partially mediated the relation between danger and cortisol slope (P = .037). Neither anxiety nor prior stress exposure was related to levels of interleukin-6. CONCLUSIONS: Because dysregulated cortisol has been related to fatigue, poorer quality of life, and shorter survival in patients with ovarian cancer, those who have prior life events and chronic anxiety during the first year postdiagnosis may be at risk for more negative outcomes. Cancer 2018. © 2018 American Cancer Society.

Changes in spiritual well-being and psychological outcomes in ovarian cancer survivors.

OBJECTIVE: Because of the poor prognosis of ovarian cancer and concomitant distress, understanding contributors to positive well-being is critical. This study examines spiritual growth as a domain of posttraumatic growth and its contribution to longitudinal emotional outcomes in ovarian cancer. METHODS: Ovarian cancer patients (N = 241) completed measures assessing spirituality (Functional Assessment of Chronic Illness Therapy-Spiritual Well-being-12; subscales: faith, meaning, and peace), depression (Center for Epidemiologic Studies Depression Scale), cancer-specific anxiety (Impact of Event Scale), and total mood disturbance (TMD; Profile of Mood States) prior to surgery and 1-year postsurgery. Stressful life events in the year after diagnosis were measured at 1-year postsurgery. Regressions examined the association between changes in spirituality and depression, anxiety, and TMD at 1-year postsurgery. Additionally, spiritual change was examined as a moderator of the effect of recent life events on mood. RESULTS: Increases in peace were related to lower depression (ß = -.40, P < .001), anxiety (ß = -.20, P = .004), and TMD (ß = -.41, P < .001) at 1 year. Changes in meaning and faith were unrelated to all outcomes. Additionally, changes in peace moderated the effect of stressful life events on depression (ß = -.14, P = .027), anxiety (ß = -.16, P = .05), and TMD (ß = -.17, P = .01), such that those with a high number of life events paired with a decrease in peace experienced the worst psychological outcomes at 1 year. CONCLUSION: These findings suggest that the quality of peace may be the most adaptive facet of spiritual growth in cancer patients. Furthermore, changes in peace appear to moderate the effect of life events on psychological well-being.

Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma.

Normal cell growth is characterized by a regulated epigenetic program that drives cellular activities such as gene transcription, DNA replication, and DNA damage repair. Perturbation of this epigenetic program can lead to events such as mis-regulation of gene transcription and diseases such as cancer. To begin to understand the epigenetic program correlated to the development of melanoma, we performed a novel quantitative mass spectrometric analysis of histone post-translational modifications mis-regulated in melanoma cell culture as well as patient tumors. Aggressive melanoma cell lines as well as metastatic melanoma were found to have elevated histone H3 Lys(27) trimethylation (H3K27me3) accompanied by overexpressed methyltransferase EZH2 that adds the specific modification. The altered epigenetic program that led to elevated H3K27me3 in melanoma cell culture was found to directly silence transcription of the tumor suppressor genes RUNX3 and E-cadherin. The EZH2-mediated silencing of RUNX3 and E-cadherin transcription was also validated in advanced stage human melanoma tissues. This is the first study focusing on the detailed epigenetic mechanisms leading to EZH2-mediated silencing of RUNX3 and E-cadherin tumor suppressors in melanoma. This study underscores the utility of using high resolution mass spectrometry to identify mis-regulated epigenetic programs in diseases such as cancer, which could ultimately lead to the identification of biological markers for diagnostic and prognostic applications.

Knee Pain and Activity Outcomes After Femoral Derotation Osteotomy for Excessive Femoral Anteversion.

BACKGROUND: Excessive femoral anteversion is a developmental condition that can become symptomatic into adolescence and manifest as anterior knee pain, tripping, and or problems with sports. Femoral derotational osteotomy about an antegrade intramedullary nail (IMN) is an accepted option to treat this condition. This is the first report of the clinical and functional outcomes of treatment of excessive anteversion with femoral derotational osteotomy stabilized with an IMN. METHODS: We prospectively enrolled 28 consecutive patients between 2013 and 2014 who underwent derotational osteotomy. Physical examination measures were used to calculate the amount of angular correction with focus on internal and external rotation of the hip, as well as the trochanteric prominence angle test of femoral anteversion. The International Knee Documentation Committee-9, Marx, and Tegner activity scales were 3 patient-reported outcomes recorded. RESULTS: After femoral derotation osteotomy over an IMN, femoral anteversion, as measured by the trochanteric prominence angle, improved an average of 29 degrees (P<0.0001). At 1-year minimum follow-up, 22 of 28 subjects (78.5%) demonstrated a mean significant improvement of 13 points for International Knee Documentation Committee-9 (SD=15.4, P=0.0007), which surpassed the level of minimal clinically important change. Furthermore, the Tegner inventory scores for the cohort improved by an average of 1.9 activity levels (SD=2.4, P=0.0012). CONCLUSIONS: For adolescents with symptomatic excessive femoral anteversion, derotational osteotomy over an IMN offers a reliable surgical option that provides predictable deformity correction and significant improvements in both function and pain scales. LEVELS OF EVIDENCE: Level II-prospective, consecutive, nonrandomized, internally controlled cohort study.

Kynurenine Signaling Increases DNA Polymerase Kappa Expression and Promotes Genomic Instability in Glioblastoma Cells.

Overexpression of the translesion synthesis polymerase hpol κ in glioblastomas has been linked to poor patient prognosis; however, the mechanism promoting higher expression in these tumors remains unknown. We determined that activation of the aryl hydrocarbon receptor (AhR) pathway in glioblastoma cells leads to increased hpol κ mRNA and protein levels. We blocked nuclear translocation and DNA binding by AhR in glioblastoma cells using a small-molecule and observed decreased hpol κ expression. Pharmacological inhibition of tryptophan-2,3-dioxygenase (TDO), the enzyme largely responsible for activating AhR in glioblastoma, led to a decrease in the endogenous AhR agonist kynurenine and a corresponding decrease in hpol κ protein levels. Importantly, we discovered that inhibiting TDO activity, AhR signaling, or suppressing hpol κ expression with RNA interference led to decreased chromosomal damage in glioblastoma cells. Epistasis assays further supported the idea that TDO activity, activation of AhR signaling, and the resulting overexpression of hpol κ function primarily in the same pathway to increase endogenous DNA damage. These findings indicate that upregulation of hpol κ through glioblastoma-specific TDO activity and activation of AhR signaling likely contributes to the high levels of replication stress and genomic instability observed in these tumors.

Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer.

BACKGROUND: The impact of psychological well-being on the physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, the authors examined how 2 different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in patients with ovarian cancer. METHODS: A total of 365 women with suspected ovarian cancer completed psychosocial assessments before surgery and clinical information was obtained from medical records. Study inclusion was confirmed after histological diagnosis. Tumor NE was measured in frozen tissue samples using high-performance liquid chromatography with electrochemical detection. Confirmatory factor analysis was used to model eudaimonic well-being, positive affect, and psychological distress, and structural equation modeling was used to examine associations between these factors and tumor NE. RESULTS: Eudaimonic well-being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (ie, compared with unitary or 2-factor models) (root mean square error of approximation, 0.048; comparative fit index, 0.982; and standardized root-mean-squared residual, 0.035). Structural equation modeling analysis that included physical well-being, stage of disease, histology, psychological treatment history, beta-blocker use, and caffeine use as covariates was found to have good model fit (root mean square error of approximation, 0.052; comparative fit index, 0.955; and standardized root-mean-squared residual, 0.036) and demonstrated that eudaimonic well-being was related to lower tumor NE (ß = -.24 [P = .045]). In contrast, no effects were found for positive affect or psychological distress. CONCLUSIONS: Eudaimonic well-being was found to be associated with lower tumor NE, independent of positive affect and psychological distress. Because adrenergic signaling is implicated in tumor progression, increasing eudaimonic well-being may improve both psychological and physiologic resilience in patients with ovarian cancer.

The dynamics of proactive and reactive cognitive control processes in the human brain.

In this study, we leveraged the high temporal resolution of EEG to examine the neural mechanisms underlying the flexible regulation of cognitive control that unfolds over different timescales. We measured behavioral and neural effects of color-word incongruency, as different groups of participants performed three different versions of color-word Stroop tasks in which the relative timing of the color and word features varied from trial to trial. For this purpose, we used a standard Stroop color identification task with equal congruent-to-incongruent proportions (50%/50%), along with two versions of the "Reverse Stroop" word identification tasks, for which we manipulated the incongruency proportion (50%/50% and 80%/20%). Two canonical ERP markers of neural processing of stimulus incongruency, the frontocentral negative polarity incongruency wave (NINC) and the late positive component (LPC), were evoked across the various conditions. Results indicated that color-word incongruency interacted with the relative feature timing, producing greater neural and behavioral effects when the task-irrelevant stimulus preceded the target, but still significant effects when it followed. Additionally, both behavioral and neural incongruency effects were reduced by nearly half in the word identification task (Reverse Stroop 50/50) relative to the color identification task (Stroop 50/50), with these effects essentially fully recovering when incongruent trials appeared only infrequently (Reverse Stroop 80/20). Across the conditions, NINC amplitudes closely paralleled RTs, indicating this component is sensitive to the overall level of stimulus conflict. In contrast, LPC amplitudes were largest with infrequent incongruent trials, suggesting a possible readjustment role when proactive control is reduced. These findings thus unveil distinct control mechanisms that unfold over time in response to conflicting stimulus input under different contexts.

Data-driven analyses to quantify information seeking behaviour for women with uterine fibroids.

Uterine fibroids (UF) are noncancerous growths of the uterus and impact the livelihood of over 26 million women in the United States. Although UF may not have accompanying symptoms, for some women their presence leads to surgical treatment, which can be a difficult decision-making process. Web-scraping of online media is used to identify information-seeking behavior of women searching for UF treatment options. We synthesize the data to describe trends in UF treatment, including the identification of gaps between the information individuals are seeking (demand) and information that is publicly available as a resource (supply), which contributes to this study's creation of the term "information desert." We perform statistical analysis to understand information-seeking behavior, determine the gap between information supply and information demand, and determine the correlation between a doctor's treatment recommendation and a patient's treatment decision as a function of age, symptoms, and knowledge obtained about specific types of treatment.