To Fluoresce or Not to Fluoresce: Investigation of Structural and Fluorescence Characteristics of CBI-Dopamine, CBI-Serotonin, and Their Structural Analogs.

Dopamine (DA) and serotonin (5-HT) are neurotransmitters that are vital for proper brain function and are implicated in a wide variety of diseases and disorders. Unfortunately, quantitative analysis of DA and 5-HT is difficult, as they are present at low concentrations in complex biological matrices. The fluorogenic reaction of napththalene-2,3-dicarboxaldehyde (NDA) with a primary amine in the presence of cyanide (CN) creates an N-substituted 1-cyanobenz[f]isoindole (CBI) derivative, whose fluorescence can be sensitively monitored in biological matrices. Given their biological importance, there are surprisingly few reports showing fluorescence of CBI-DA and no prior publications concerning CBI-5-HT. In this work, nuclear magnetic resonance spectroscopy (NMR) was employed to determine the atom connectivity of over 10 CBI-products, including CBI-DA and CBI-5-HT. NMR and fluorescence spectroscopy were applied to CBI-DA, CBI-5-HT, and select structural analogs to determine structural correlations with the observed lack of fluorescence. Experiments with CBI-DA and structural analogs indicated fluorescence was rapidly quenched due to both complexation with the historically employed buffer and oxidation in solution. Fluorescence of CBI-DA was recovered by modifying the derivatization background to prevent complexation and oxidation. In contrast, fluorescence characterization of CBI-5-HT and its structural analogs indicated that 5-HT was acting as a quencher of the CBI-ring. The addition of acid to protonate 5-HT was found to disrupt this interaction and enable the first reported fluorescence detection of CBI-5-HT. In the future, this work will be applied to detect DA and 5-HT in biological systems to gain insight into neurobiological disease states and disorders.

Optimized derivatization of primary amines with the fluorogenic reagent naphthalene-2,3-dicarboxaldehyde toward reproducible quantitative analysis in biological systems.

Primary amines are the target of many bioanalytical analyses, as they are ubiquitous in biological systems and responsible for numerous important processes including neurotransmission and cell signaling. Primary amines can be sensitively detected via fluorescence after their reaction with the fluorogenic reagent naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide through the formation of fluorescent N-substituted 1-cyanobenz[f]isoindole (CBI) derivatives. While fluorogenic reagents such as NDA can be advantageous for sensitive detection, improvements in both long-term stability and speed of reaction are necessary to enable practical and reproducible quantitative analysis. In this work, various CBI-amines were interrogated for their fluorescence characteristics over time under previously reported conditions (75:25 aqueous buffer:acetonitrile). An amine-specific decline in fluorescence and delay to reach maximum fluorescence were observed. Based on structural characteristics, we hypothesized that these effects were due to the solvents employed enabling analyte intermolecular interactions that resulted in fluorescence quenching over time. To mitigate fluorescence-quenching intermolecular interactions, we developed two strategies to improve the fluorescence of the CBI-product over long time periods: (1) the addition of the complexation reagent ß-cyclodextrin to the reaction matrix and (2) the substitution of acetonitrile with dimethyl sulfoxide. Both strategies improved fluorescence stability over time, and the incorporation of dimethyl sulfoxide also enabled more rapid attainment of maximum fluorescence and a higher absolute fluorescence when compared to initial conditions. When employed in combination, these two approaches further improve fluorescence stability over time for the most hydrophobic analytes. In the future, these strategies can be employed for the practical and reproducible quantitative analysis of primary amines in biological systems, including those related to neurological disorders and disease states.

Visible Light-Mediated, Diastereoselective Epimerization of Morpholines and Piperazines to More Stable Isomers.

We report a photocatalyzed epimerization of morpholines and piperazines that proceeds by reversible hydrogen atom transfer (HAT) and provides an efficient strategy for editing the stereochemical configurations of these saturated nitrogen heterocycles, which are prevalent in drugs. The more stable morpholine and piperazine isomers are obtained from the more synthetically accessible but less stable stereoisomers, and a broad scope is demonstrated in terms of substitution patterns and functional group compatibility. The observed distributions of diastereomers correlate well with the relative energies of the diastereomer pairs as determined by density functional theory (DFT) calculations. Mechanistic studies, including luminescence quenching, deuterium labeling reactions, and determination of reversibility support a thiyl radical mediated HAT pathway for the epimerization of morpholines. Investigation of piperazine epimerization established that the mechanism is more complex and led to the development of thiol free conditions for the highly stereoselective epimerization of N,N'-dialkyl piperazines for which a previously unrecognized radical chain HAT mechanism is proposed.

Distribution of contaminants in the environment and wildlife habitat use: a case study with lead and waterfowl on the Upper Texas Coast.

The magnitude and distribution of lead contamination remain unknown in wetland systems. Anthropogenic deposition of lead may be contributing to negative population-level effects in waterfowl and other organisms that depend on dynamic wetland habitats, particularly if they are unable to detect and differentiate levels of environmental contamination by lead. Detection of lead and behavioral response to elevated lead levels by waterfowl is poorly understood, but necessary to characterize the risk of lead-contaminated habitats. We measured the relationship between lead contamination of wetland soils and habitat use by mottled ducks (Anas fulvigula) on the Upper Texas Coast, USA. Mottled ducks have historically experienced disproportionate negative effects from lead exposure, and exhibit a unique nonmigratory life history that increases risk of exposure when inhabiting contaminated areas. We used spatial interpolation to estimate lead in wetland soils of the Texas Chenier Plain National Wildlife Refuge Complex. Soil lead levels varied across the refuge complex (0.01-1085.51 ppm), but greater lead concentrations frequently corresponded to areas with high densities of transmittered mottled ducks. We used soil lead concentration data and MaxENT species distribution models to quantify relationships among various habitat factors and locations of mottled ducks. Use of habitats with greater lead concentration increased during years of a major disturbance. Because mottled ducks use habitats with high concentrations of lead during periods of stress, have greater risk of exposure following major disturbance to the coastal marsh system, and no innate mechanism for avoiding the threat of lead exposure, we suggest the potential presence of an ecological trap of quality habitat that warrants further quantification at a population scale for mottled ducks.

Incorporating Economic Policy Into A 'Health-In-All-Policies' Agenda.

Recognizing the health effects of nonhealth policies, scholars and others seeking to improve Americans' health have advocated the implementation of a culture of health-which would call attention to and prioritize health as a key outcome of policy making across all levels of government and in the private sector. Adopting this "health-in-all-policies" lens, policy makers are paying increasing attention to health impacts as they debate policies in areas such as urban planning, housing, and transportation. Yet the health impacts of economic policies that shape the distribution of income and wealth are often overlooked. Pooling data from all fifty states for the period 1990-2010, we provide a broad portrait of how economic policies affect health. Overall, we found better health outcomes in states that enacted higher tax credits for the poor or higher minimum wage laws and in states without a right-to-work law that limits union power. Notably, these policies focus on increasing the incomes of low-income and working-class families, instead of on shaping the resources available to wealthier individuals. Incorporating these findings into a health-in-all-policies agenda will require leadership from the health sector, including a willingness to step into core and polarizing debates about redistribution.

Party politics and enactment of "Obamacare": a policy-centered analysis of minority party involvement.

The Patient Protection and Affordable Care Act of 2010 (ACA) passed with no Republican votes and was accompanied by intense criticism that the reform was "rammed through" the legislative process by the majority party. By contrast, many Democrats emphasized the extensive yearlong debate over health care reform and argued that the final bill represented a compromise of good ideas from both parties. We undertake a policy-centered analysis to help reconcile these conflicting reports of this legislative episode. Drawing on real-time accounts published in the Capitol Hill newspaper Roll Call, we compare the success of Democratic and Republican Parties' policy proposals in terms of centrality to the policy agenda and inclusion in the enacted legislation. Our findings indicate that Republican-backed proposals were more present on the policy agenda than in the final legislation--although both were dominated by Democratic policy proposals. In this case, the major limit on majority party power seemed to be intraparty conflict, rather than opposition from the minority party.

How the National Prevention Council can overcome key challenges and improve Americans' health.

The Affordable Care Act of 2010 established the first-ever National Prevention, Health Promotion, and Public Health Council out of recognition of the need for a major new national focus on disease prevention. Composed of cabinet-level officials from a range of federal agencies, the council has a clear policy mandate: to coordinate and lead prevention, wellness, and health promotion efforts across the entire federal government and the nation. In its first year, the council developed a comprehensive prevention strategy; but its full implementation is threatened by economic, political, bureaucratic, and institutional challenges. This article examines these challenges and makes recommendations for how to maximize the positive impact of the council through effective cross-agency collaboration aimed at improving Americans' health, including framing prevention as a bipartisan cost containment strategy; distancing the work of the council from the implementation of other aspects of the Affordable Care Act; using dollars from the Prevention and Public Health Fund to incentivize ongoing participation by nonhealth agencies; and providing technical assistance and analytic support to nonhealth agencies willing to broaden attention to the health impacts of their nonhealth policies.

The Impact of Child Care Subsidy Use on Child Care Quality.

In 2008, the federal government allotted $7 billion in child care subsidies to low-income families through the state-administered Child Care and Development Fund (CCDF), now the government's largest child care program (US DHHS, 2008). Although subsidies reduce costs for families and facilitate parental employment, it is unclear how they impact the quality of care families purchase. This study investigates the impact of government subsidization on parents' selection of child care quality using multivariate regression and propensity score matching approaches to account for differential selection into subsidy receipt and care arrangements. Data were drawn from the Child Care Supplement to the Fragile Families and Child Wellbeing Study (CCS-FFCWS), conducted in 2002 and 2003 in 14 of the 20 FFCWS cities when focal children were 3 years old (N = 456). Our results indicate that families who used subsidies chose higher quality care than comparable mothers who did not use subsidies, but only because subsidy recipients were more likely to use center-based care. Subgroup analyses revealed that families using subsidies purchased higher-quality home-based care but lower-quality center-based care than comparable non-recipients. Findings suggest that child care subsidies may serve as more than a work support for low-income families by enhancing the quality of nonmaternal care children experience but that this effect is largely attributable to recipients' using formal child care arrangements (versus kith and kin care) more often than non-recipients.

Federal food policy and childhood obesity: a solution or part of the problem?

Amid growing concern about childhood obesity, the United States spends billions of dollars on food assistance: providing meals and subsidizing food purchases. We examine the relationship between food assistance and body mass index (BMI) for young, low-income children, who are a primary target population for federal food programs and for efforts to prevent childhood obesity. Our findings indicate that food assistance may unintentionally contribute to the childhood obesity problem in cities with high food prices. We also find that subsidized meals at school or day care are beneficial for children's weight status, and we argue that expanding access to subsidized meals may be the most effective tool to use in combating obesity in poor children.

Public values, health inequality, and alternative notions of a "fair" response.

The fact that disadvantaged people generally die younger and suffer more disease than those with more resources is gaining ground as a major policy concern in the United States. Yet we know little about how public values inform public opinion about policy interventions to address these disparities. This article presents findings from an exploratory study of the public's values and priorities as they relate to social inequalities in health. Forty-three subjects were presented with a scenario depicting health inequalities by social class and were given the opportunity to alter the distribution of health outcomes. Participants' responses fell into one of three distributive preferences: (1) prioritize the disadvantaged, (2) equalize health outcomes between advantaged and disadvantaged groups, and (3) equalize health resources between advantaged and disadvantaged groups. These equality preferences were reflected in participants' responses to a second, more complex scenario in which trade-offs with other health-related values - maximizing health and prioritizing the sickest - were introduced. In most cases, participants moderated their distributive preferences to accommodate these other health goals, particularly to prioritize the allocation of resources to the very sick regardless of their socioeconomic status.

Public views on determinants of health, interventions to improve health, and priorities for government.

OBJECTIVE: There is increasing evidence about the importance of factors that impact health beyond health care and individual behavior, yet there is little public and policy discourse about these things in the United States. We surveyed Wisconsin adults to see what they think are the most important factors that affect health. We also examined which interventions they believe would improve health, and whether government should prioritize such interventions. METHODS: A phone survey of a random sample of 1459 Wisconsin adults was conducted between September 2006 and February 2007. RESULTS: The Wisconsin public believes that health practices, access to health care, and health insurance are the most important factors affecting health, and that health insurance is a high government priority. Other broader social and economic determinants of health, such as employment, social support, income, housing, and neighborhood factors are seen as less important to health. Although respondents believe that health practices are important to health, they are less likely to suggest that government prioritize improving individual health practices. Although the public believes the government should prioritize access to health care and health insurance, they are not as likely to support government implementing social or economic policies in order to improve health. CONCLUSION: In light of research demonstrating the importance of social and economic determinants of health, and of ongoing public forums meant to raise awareness of these determinants of health, it will be important to track whether public opinion of Wisconsin adults changes over time to increase attention to the social and economic determinants of health and related policy initiatives.