Solvent-Dependent Emissions Properties of a Model Aurone Enable Use in Biological Applications.

Fluorophores are powerful visualization tools and the development of novel small organic fluorophores are in great demand. Small organic fluorophores have been derived from the aurone skeleton, 2-benzylidenebenzofuran-3(2H)-one. In this study, we have utilized a model aurone derivative with a methoxy group at the 3' position and a hydroxyl group at the 4' position, termed vanillin aurone, to develop a foundational understanding of structural factors impacting aurone fluorescence properties. The fluorescent behaviors of the model aurone were characterized in solvent environments differing in relative polarity and dielectric constant. These data suggested that hydrogen bonding or electrostatic interactions between excited state aurone and solvent directly impact emissions properties such as peak emission wavelength, emission intensity, and Stokes shift. Time-dependent Density Functional Theory (TD-DFT) model calculations suggest that quenched aurone emissions observed in water are a consequence of stabilization of a twisted excited state conformation that disrupts conjugation. In contrast, the calculations indicate that low polarity solvents such as toluene or acetone stabilize a brightly fluorescent planar state. Based on this, additional experiments were performed to demonstrate use as a turn-on probe in an aqueous environment in response to conditions leading to planar excited state stabilization. Vanillin aurone was observed to bind to a model ATP binding protein, YME1L, leading to enhanced emissions intensities with a dissociation equilibrium constant equal to ~ 30 µM. Separately, the aurone was observed to be cell permeable with significant toxicity at doses exceeding 6.25 µM. Taken together, these results suggest that aurones may be broadly useful as turn-on probes in aqueous environments that promote either a change in relative solvent polarity or through direct stabilization of a planar excited state through macromolecular binding.

An Innovative Approach to Using Electronic Health Records Through Health Information Exchange to Build a Chronic Disease Registry in Michigan.

Michigan's CHRONICLE, the Chronic Disease Registry Linking Electronic Health Record Data, is a near-real-time disease monitoring system designed to harness electronic health record (EHR) data and existing health information exchange (HIE) infrastructure for transformative public health surveillance. Strong evidence indicates that using EHR data in chronic disease monitoring will provide rapid insight over time on health care use, outcomes, and public health interventions. We examined the potential of EHR data for chronic disease surveillance through close collaboration with our statewide HIE network and 2 participating health systems. We describe the development of CHRONICLE, the promising findings from its implementation, the identified challenges, and how those challenges will inform the next steps in testing, refining, and expanding the system. By detailing our approach to developing CHRONICLE and the considerations and early steps required to build an innovative, EHR-based chronic disease registry, we aim to inform public health leaders and professionals on the value of EHR data for chronic disease surveillance. With systematic testing, evaluation, and enhancement, our goal for CHRONICLE, as a fully realized and comprehensive surveillance system, is to model how collaborative health information exchange can support evidence-based strategies, resource allocation, and precision in disease monitoring.

Disparities in genetic services utilization in a random sample of young breast cancer survivors.

PURPOSE: Increasing use of genetic services (counseling/testing) among young breast cancer survivors (YBCS) can help decrease breast cancer incidence and mortality. The study examined use of genetic services between Black and White/Other YBCS, attitudes and knowledge of breast cancer risk factors, and reasons for disparities in using genetic services. METHODS: We used baseline data from a randomized control trial including a population-based, stratified random sample of 3000 potentially eligible YBCS, with oversampling of Black YBCS. RESULTS: Among 883 YBCS (353 Black, 530 White/Other) were significant disparities between the two racial groups. More White/Other YBCS had received genetic counseling and had genetic testing than Blacks. Although White/Other YBCS resided farther away from board-certified genetic counseling centers, they had fewer barriers to access these services. Black race, high out-of-pocket costs, older age, and more years since diagnosis were negatively associated with use of genetic services. Black YBCS had lower knowledge of breast cancer risk factors. Higher education and genetic counseling were associated with higher genetic knowledge. CONCLUSION: Racial inequalities of cost-related access to care and education create disparities in genetic services utilization. System-based interventions that reduce socioeconomic disparities and empower YBCS with genetic knowledge, as well as physician referrals, can increase access to genetic services.

Surveillance for cancer recurrence in long-term young breast cancer survivors randomly selected from a statewide cancer registry.

PURPOSE: This study examined clinical breast exam (CBE) and mammography surveillance in long-term young breast cancer survivors (YBCS) and identified barriers and facilitators to cancer surveillance practices. METHODS: Data collected with a self-administered survey from a statewide, randomly selected sample of YBCS diagnosed with invasive breast cancer or ductal carcinoma in situ younger than 45 years old, stratified by race (Black vs. White/Other). Multivariate logistic regression models identified predictors of annual CBEs and mammograms. RESULTS: Among 859 YBCS (n = 340 Black; n = 519 White/Other; mean age = 51.0 ± 5.9; diagnosed 11.0 ± 4.0 years ago), the majority (> 85%) reported an annual CBE and a mammogram. Black YBCS in the study were more likely to report lower rates of annual mammography and more barriers accessing care compared to White/Other YBCS. Having a routine source of care, confidence to use healthcare services, perceived expectations from family members and healthcare providers to engage in cancer surveillance, and motivation to comply with these expectations were significant predictors of having annual CBEs and annual mammograms. Cost-related lack of access to care was a significant barrier to annual mammograms. CONCLUSIONS: Routine source of post-treatment care facilitated breast cancer surveillance above national average rates. Persistent disparities regarding access to mammography surveillance were identified for Black YBCS, primarily due to lack of access to routine source of care and high out-of-pocket costs. IMPLICATIONS: Public health action targeting cancer surveillance in YBCS should ensure routine source of post-treatment care and address cost-related barriers. Clinical Trials Registration Number: NCT01612338.

Recruiting families at risk for hereditary breast and ovarian cancer from a statewide cancer registry: a methodological study.

PURPOSE: Cancer genetic services (counseling/testing) are recommended for women diagnosed with breast cancer younger than 45 years old (young breast cancer survivors-YBCS) and at-risk relatives. We present recruitment of YBCS, identification and recruitment of at-risk relatives, and YBCS willingness to contact their cancer-free, female relatives. METHODS: A random sample of 3,000 YBCS, stratified by race (Black vs. White/Other), was identified through a population-based cancer registry and recruited in a randomized trial designed to increase use of cancer genetic services. Baseline demographic, clinical, and family characteristics, and variables associated with the Theory of Planned Behavior (TPB) were assessed as predictors of YBCS' willingness to contact at-risk relatives. RESULTS: The 883 YBCS (33.2% response rate; 40% Black) who returned a survey had 1,875 at-risk relatives and were willing to contact 1,360 (72.5%). From 853 invited at-risk relatives (up to two relatives per YBCS), 442 responded (51.6% response rate). YBCS with larger families, with a previous diagnosis of depression, and motivated to comply with recommendations from family members were likely to contact a greater number of relatives. Black YBCS were more likely to contact younger relatives and those living further than 50 miles compared to White/Other YBCS. CONCLUSION: It is feasible to recruit diverse families at risk for hereditary cancer from a population-based cancer registry. This recruitment approach can be used as a paradigm for harmonizing processes and increasing internal and external validity of large-scale public health genomic initiatives in the era of precision medicine.

Public awareness of genetic nondiscrimination laws in four states and perceived importance of life insurance protections.

Genetic testing has grown dramatically in the past decade and is becoming an integral part of health care. Genetic nondiscrimination laws have been passed in many states, and the Genetic Information Nondiscrimination Act (GINA) was passed at the federal level in 2008. These laws generally protect individuals from discrimination by health insurers or employers based on genetic information, including test results. In 2010, Connecticut, Michigan, Ohio, and Oregon added four questions to their Behavioral Risk Factor Surveillance System (BRFSS) survey to assess interest in genetic testing, awareness of genetic nondiscrimination laws, concern about genetic discrimination in determining life insurance eligibility and cost, and perceived importance of genetic nondiscrimination laws that address life insurance. Survey results showed that awareness of genetic nondiscrimination laws was low (less than 20 % of the adult population), while perceived importance of these types of laws was high (over 80 % of respondents rated them as very or somewhat important). Over two-thirds of respondents indicated they were very or somewhat concerned about life insurance companies using genetic test results to determine life insurance coverage and costs. Results indicate a need for more public education to raise awareness of protections provided through current genetic nondiscrimination laws. The high rate of concern about life insurance discrimination indicates an additional need for continued dialogue regarding the extent of legal protections in genetic nondiscrimination laws.

Using a state cancer registry to recruit young breast cancer survivors and high-risk relatives: protocol of a randomized trial testing the efficacy of a targeted versus a tailored intervention to increase breast cancer screening.

BACKGROUND: The Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer. METHODS/DESIGN: The study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20-45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors' high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors': a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives' baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention. DISCUSSION: The study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics.

Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers.

BACKGROUND: Heavy drinkers show altered functional magnetic resonance imaging (fMRI) response to alcohol cues. Little is known about alcohol cue reactivity among college age drinkers, who show the greatest rates of alcohol use disorders. Family history of alcoholism (family history positive [FHP]) is a risk factor for problematic drinking, but the impact on alcohol cue reactivity is unclear. We investigated the influence of heavy drinking and family history of alcoholism on alcohol cue-related fMRI response among college students. METHODS: Participants were 19 family history negative (FHN) light drinkers, 11 FHP light drinkers, 25 FHN heavy drinkers, and 10 FHP heavy drinkers, aged 18 to 21. During fMRI scanning, participants viewed alcohol images, nonalcohol beverage images, and degraded control images, with each beverage image presented twice. We characterized blood oxygen level-dependent (BOLD) contrast for alcohol versus nonalcohol images and examined BOLD response to repeated alcohol images to understand exposure effects. RESULTS: Heavy drinkers exhibited greater BOLD response than light drinkers in posterior visual association regions, anterior cingulate, medial frontal cortex, hippocampus, amygdala, and dorsal striatum, and hyperactivation to repeated alcohol images in temporo-parietal, frontal, and insular regions (clusters > 8,127 µl, p < 0.05). FHP individuals showed increased activation to repeated alcohol images in temporo-parietal regions, fusiform, and hippocampus. There were no interactions between family history and drinking group. CONCLUSIONS: Our results parallel findings of hyperactivation to alcohol cues among heavy drinkers in regions subserving visual attention, memory, motivation, and habit. Heavy drinkers demonstrated heightened activation to repeated alcohol images, which could influence continued drinking. Family history of alcoholism was associated with greater response to repeated alcohol images in regions underlying visual attention, recognition, and encoding, which could suggest aspects of alcohol cue reactivity that are independent of personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity.

Public awareness and use of direct-to-consumer personal genomic tests from four state population-based surveys, and implications for clinical and public health practice.

PURPOSE: Direct-to-consumer personal genomic tests are widely available, but population-based data are limited on awareness and use of these tests among the general public in the United States. METHODS: We assessed awareness and use of direct-to-consumer personal genomic tests in Connecticut, Michigan, Oregon, and Utah using the 2009 Behavioral Risk Factor Surveillance System and compared the state results to the 2008 national HealthStyles survey results. RESULTS: Awareness was the highest in Oregon (29.1%) and the lowest in Michigan (15.8%). Factors associated with awareness across all states and nationally were higher education, higher income, and increasing age, except among those 75 years or older. Less than 1% of respondents had used the tests, with about one-half to three-quarters of those sharing the results with a health-care provider. CONCLUSIONS: Awareness of direct-to-consumer genetic tests is greater in this study as compared with a related study conducted in 2006, whereas use is similarly low in both studies. The few respondents who reported using the tests often reported sharing their results with their health-care provider, indicating an important opportunity for health-care providers to offer patient education regarding these tests. Public health agencies have important roles in surveillance, education, and policy development on direct-to-consumer genomic tests.

Food cue reactivity in successful laparoscopic gastric banding: A sham-deflation-controlled pilot study.

Laparoscopic adjustable gastric banding (LAGB) offers a unique opportunity to examine the underlying neuronal mechanisms of surgically assisted weight loss due to its instant, non-invasive, adjustable nature. Six participants with stable excess weight loss (%EWL ≥ 45) completed 2 days of fMRI scanning 1.5-5 years after LAGB surgery. In a within-subject randomized sham-controlled design, participants underwent (sham) removal of ∼ 50% of the band's fluid. Compared to sham-deflation (i.e., normal band constriction) of the band, in the deflation condition (i.e., decreasing restriction) participants showed significantly lower activation in the anterior (para)cingulate, angular gyrus, lateral occipital cortex, and frontal cortex in response to food images (p < 0.05, whole brain TFCE-based FWE corrected). Higher activation in the deflation condition was seen in the fusiform gyrus, inferior temporal gyrus, lingual gyrus, lateral occipital cortex. The findings of this within-subject randomized controlled pilot study suggest that constriction of the stomach through LAGB may indirectly alter brain activation in response to food cues. These neuronal changes may underlie changes in food craving and food preference that support sustained post-surgical weight-loss. Despite the small sample size, this is in agreement with and adds to the growing literature of post-bariatric surgery changes in behavior and control regions.

Functional imaging of cognitive control during acute alcohol intoxication.

BACKGROUND: The anterior cingulate and several other prefrontal and parietal brain regions are implicated in error processing and cognitive control. The effects of different doses of alcohol on activity within these brain regions during a functional magnetic resonance imaging (fMRI) task where errors are frequently committed have not been fully explored. METHODS: This study examined the impact of a placebo [breath alcohol concentration (BrAC) = 0.00%], moderate (BrAC = 0.05%), and high (BrAC = 0.10%) doses of alcohol on brain hemodynamic activity during a functional MRI (fMRI) Go/No-Go task in 38 healthy volunteers. RESULTS: Alcohol increased reaction time and false alarm errors in a dose-dependent manner. fMRI analyses showed alcohol decreased activity in anterior cingulate, lateral prefrontal cortex, insula, and parietal lobe regions during false alarm responses to No-Go stimuli. CONCLUSIONS: These findings indicate that brain regions implicated in error processing are affected by alcohol and might provide a neural basis for alcohol's effects on behavioral performance.

Fast-food consumption and obesity among Michigan adults.

INTRODUCTION: Consumption of meals eaten away from home, especially from fast-food restaurants, has increased in the United States since the 1970s. The main objective of this study was to examine the frequency and characteristics of fast-food consumption among adults in Michigan and obesity prevalence. METHODS: We analyzed data from 12 questions about fast-food consumption that were included on the 2005 Michigan Behavioral Risk Factor Survey, a population-based telephone survey of Michigan adults, using univariate and bivariate analyses and multivariate logistic regression, and compared these data with data on Michigan obesity prevalence. RESULTS: Approximately 80% of Michigan adults went to fast-food restaurants at least once per month and 28% went regularly (≥2 times/wk). Regular fast-food consumption was higher among younger adults (mostly men) but was not significantly associated with household income, education, race, or urbanicity (in a multivariate framework). The prevalence of obesity increased consistently with frequenting fast-food restaurants, from 24% of those going less than once a week to 33% of those going 3 or more times per week. The predominant reason for choosing fast food was convenience. Although hypothetically 68% of adults who go to fast-food restaurants would choose healthier fast-food items when available, only 16% said they ever use nutritional information when ordering. CONCLUSION: The prevalence of fast-food consumption is high in Michigan across education, income, and racial groups and is strongly associated with obesity. Making nutritional information at fast-food restaurants more readily available and easier to use may help consumers to order more healthful or lower-calorie items.

Altered neural activity and emotions following right middle cerebral artery stroke.

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims.

Tool to assess the cost and quality benefits of nursing innovation.

Understanding the economic value of nursing services in a time of unprecedented public sector cuts is a challenge. The economic assessment tool (EAT) (RCN 2011) has been designed by the authors of the article for this purpose and generates return on investment dividends for nursing innovations and services. The EAT, which is built on the discipline of improvement and uses many of its tools and techniques, involves four stages: mapping, costing, calculating and reporting. The nursing profession systematically captures a range of clinical data as part of routine care to which monetary values can be assigned. The EAT exploits these data and provides the profession with the economic evidence it might need to sustain quality nursing services in financially uncertain times.

Sex, drugs, and cognition: effects of marijuana.

Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n=35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana including attention, cognitive flexibility, time estimation, and visuospatial processing. As expected, acute marijuana use impaired performance on selective and divided attention, time estimation, and cognitive flexibility. While there did not appear to be sex differences in marijuana's effects on cognition, women requested to discontinue the smoking session more often than men, likely leading to an underestimation of differences. Further study of psychological differences in marijuana's effects on men and women following both acute and residual effects of marijuana is warranted.

Sex differences in the effects of marijuana on simulated driving performance.

In the United States, one in six teenagers has driven under the influence of marijuana. Driving under the influence of marijuana and alcohol is equally prevalent, despite the fact that marijuana use is less common than alcohol use. Much of the research examining the effects of marijuana on driving performance was conducted in the 1970s and led to equivocal findings. During that time, few studies included women and driving simulators were rudimentary. Further, the potency of marijuana commonly used recreationally has increased. This study examined sex differences in the acute effects of marijuana on driving performance using a realistic, validated driving simulator. Eighty-five subjects (n = 50 males, 35 females) participated in this between-subjects, double-blind, placebo controlled study. In addition to an uneventful, baseline segment of driving, participants were challenged with collision avoidance and distracted driving scenarios. Under the influence of marijuana, participants decreased their speed and failed to show expected practice effects during a distracted drive. No differences were found during the baseline driving segment or collision avoidance scenarios. No differences attributable to sex were observed. This study enhances the current literature by identifying distracted driving and the integration of prior experience as particularly problematic under the influence of marijuana.

Knowledge of tissue plasminogen activator for acute stroke among Michigan adults.

BACKGROUND AND PURPOSE: Although tissue plasminogen activator (tPA) is an effective therapy for acute ischemic stroke, treatment rates remain low. Efforts to address the underuse of tPA include public education to increase the recognition of stroke symptoms and the awareness of tPA treatment. Our objective was to determine the level of knowledge about tPA treatment for acute stroke among a representative sample of Michigan adults. METHODS: The Michigan Behavioral Risk Factor Survey (BRFS) is a random-digit-dial telephone survey of adults conducted annually as part of the national BRFS. Questions regarding tPA treatment for acute stroke were included in the 2004 Michigan BRFS. We examined the prevalence of awareness using chi(2) tests and generated multivariable logistic regression models. RESULTS: Among 4724 respondents, only 32.2% (95% CI=30.8 to 33.8%) were aware of the existence of tPA treatment for acute stroke, of whom 52.7% (50.0 to 55.4%) knew that it needed to be administered within 3 hours of symptom onset. Awareness of tPA was higher among middle aged adults, females, whites, and those with higher education and income. Awareness of the time window for tPA was higher among middle aged adults and whites. CONCLUSIONS: In this population-based survey only a third of the public were aware of tPA as a treatment for stroke, and only 1 in 6 were aware that the treatment exists and needs to be given within 3 hours of symptom onset. Continuing efforts are necessary to increase public knowledge about tPA treatment for acute stroke.

Racial disparities in knowledge of stroke and heart attack risk factors and warning signs among Michigan adults.

OBJECTIVE: To describe the level of knowledge regarding risk factors and warning signs for stroke and heart attack among White and African American adults in Michigan and to quantify racial disparities. METHODS: Knowledge of stroke and heart attack risk factors and warning signs was assessed by using data from the 2004 Michigan Behavioral Risk Factor Survey. Prevalence estimates of knowledge were generated, and statistical differences in knowledge between Whites and African Americans were assessed. Adequate knowledge was defined as knowing 3 correct warning signs or risk factors. Logistic regression models were used to quantify the racial disparity in knowledge while controlling for potential confounding. RESULTS: Whites had substantially higher levels of adequate knowledge of risk factors (stroke: 31.6% vs 13.8%; heart attack: 52.6% vs 24.3%) and warning signs (stroke: 30.0% vs 17.2%; heart attack: 29.3% vs 13.8%) compared with African Americans (all observed differences were significant at P < .05). The odds of adequate knowledge of risk factors (stroke: adjusted odds ratio [AOR] 2.9; heart attack: AOR 3.4) and warning signs (stroke: AOR 2.0; heart attack: AOR 2.4) were significantly higher for Whites than for African Americans. CONCLUSION: A strong racial disparity in the knowledge of stroke and heart attack risk factors and warning signs exists among Michigan adults. Communitywide public education programs in conjunction with targeted interventions for at-risk populations are necessary to produce meaningful improvements in the awareness of stroke and heart attack risk factors and warning signs among Michigan adults.