Trafficking of JC virus-like particles across the blood-brain barrier.

Hollow viral vectors, such as John Cunningham virus-like particles (JC VLPs), provide a unique opportunity to deliver drug cargo into targeted cells and tissue. Current understanding of the entry of JC virus in brain cells has remained insufficient. In particular, interaction of JC VLPs with the blood-brain barrier (BBB) has not been analyzed in detail. Thus, JC VLPs were produced in this study for investigating the trafficking across the BBB. We performed a carotid artery injection procedure for mouse brain to qualitatively study JC VLPs' in vivo binding and distribution and used in vitro approaches to analyze their uptake and export kinetics in brain endothelial cells. Our results show that clathrin-dependent mechanisms contributed to the entry of VLPs into brain endothelial cells, and exocytosis or transcytosis of VLPs across the BBB was observed in vitro. VLPs were found to interact with sialic acid glycans in mouse brain endothelia. The ability of JC VLPs to cross the BBB can be useful in developing a delivery system for transport of genes and small molecule cargoes to the brain.

Impact of Local Boards of Health on Local Health Department Accreditation, Community Health Assessment, Community Health Improvement Planning, and Strategic Planning.

INTRODUCTION: Local health departments (LHDs) are increasingly using national standards to meet the challenges presented by the complex environments in which these agencies operate. Local boards of health (LBoHs) might play an instrumental role in improving LHDs' engagement in activities to meet these standards. OBJECTIVES: To assess the impact of LBoH performance of governance functions on LHDs having a current (completed within 5 years) community health assessment (CHA), community health improvement plan (CHIP), strategic plan, and level of engagement in the Public Health Accreditation Board (PHAB) accreditation program. METHODS: Binary and multinomial logistic regression models were used to analyze linked data from 329 LHDs participating in both the 2015 Local Board of Health Survey and the 2016 National Profile of LHDs Survey. RESULTS: Higher performance of LBoH governance functions, measured by an overall scale of LBoH taxonomy consisting of 60 items, had a significant positive effect on LHDs having completed CHA (P < .001), CHIP (P = .01), and strategic plan (P < .001). LHDs operating in communities with a higher score on the overall scale of LBoH taxonomy had significantly higher odds (P = .03) of having higher level of participation in the PHAB national voluntary accreditation program-that is, being accredited, having submitted application for accreditation, or being in the e-PHAB system (eg, by submitting a letter of intent). CONCLUSIONS: LBoHs serve as governance bodies for roughly 71% of LHDs and can play a significant role in encouraging LHDs' participation in these practices. That positive influence of LBoHs can be seen more clearly if the complexity and richness of LBoH governance functions and other characteristics are measured appropriately. The study findings suggest that LBoHs are a significant component of the public health system in the United States, having positive influence on LHDs having a CHA, CHIP, strategic plan, and participation in accreditation.

Inborn vs. acquired anxiety in cross-breeding and cross-fostering HAB/LAB mice bred for extremes in anxiety-related behavior.

This study focused on genetically determined versus acquired factors in shaping anxiety-related behavior by combining cross-breeding and cross-fostering approaches. Via cross-breeding of HAB (high anxiety-related behavior) female and LAB (low anxiety-related behavior) male mice, we obtained F1 hybrids with intermediate anxiety levels carrying genetic characteristics of both parental lines. Pups were raised either by their biological HAB (noncross-fostered control) or foster LAB (cross-fostered) mothers. Compared to controls, 6-week-old offspring raised by LAB mothers showed lower levels of anxiety in the elevated plus-maze and open field, but not the light-dark box, tests. No differences were found in the forced swim test reflecting active versus passive coping. The behavioral changes were associated with increased stress-induced concentrations of plasma corticosterone in cross-fostered animals. The expression of the corticotropin-releasing hormone receptor type I and glucocorticoid receptor genes did not differ in limbic and hypothalamic brain areas between cross-fostered and control mice. The data suggest that LAB-typical maternal care may partially shift behavioral and neuroendocrine characteristics of F1 crosses carrying both HAB and LAB alleles from intermediate toward reduced anxiety-related behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.

BACKGROUND: Pathological anxiety originates from a complex interplay of genetic predisposition and environmental factors, acting via epigenetic mechanisms. Epigenetic processes that can counteract detrimental genetic risk towards innate high anxiety are not well characterized. METHODS: We used female mouse lines of selectively bred high (HAB)- vs low (LAB)-innate anxiety-related behavior and performed select environmental and pharmacological manipulations to alter anxiety levels as well as brain-specific manipulations and immunohistochemistry to investigate neuronal mechanisms associated with alterations in anxiety-related behavior. RESULTS: Inborn hyperanxiety of high anxiety-like phenotypes was effectively reduced by environmental enrichment exposure. c-Fos mapping revealed that hyperanxiety in high anxiety-like phenotypes was associated with blunted challenge-induced neuronal activation in the cingulate-cortex, which was normalized by environmental enrichment. Relating this finding with epigenetic modifications, we found that high anxiety-like phenotypes (compared with low-innate anxiety phenotypes) showed reduced acetylation in the hypoactivated cingulate-cortex neurons following a mild emotional challenge, which again was normalized by environmental enrichment. Paralleling the findings using environmental enrichment, systemic administration of histone-deacetylase-inhibitor MS-275 elicited an anxiolytic-like effect, which was correlated with increased acetylated-histone-3 levels within cingulate-cortex. Finally, as a proof-of-principle, local MS-275 injection into cingulate-cortex rescued enhanced innate anxiety and increased acetylated-histone-3 within the cingulate-cortex, suggesting this epigenetic mark as a biomarker for treatment success. CONCLUSIONS: Taken together, the present findings provide the first causal evidence that the attenuation of high innate anxiety-like behavior via environmental/pharmacological manipulations is epigenetically mediated via acetylation changes within the cingulate-cortex. Finally, histone-3 specific histone-deacetylase-inhibitor could be of therapeutic importance in anxiety disorders.

Polymorphism in Tmem132d regulates expression and anxiety-related behavior through binding of RNA polymerase II complex.

TMEM132D is a candidate gene, where risk genotypes have been associated with anxiety severity along with higher mRNA expression in the frontal cortex of panic disorder patients. Concurrently, in a high (HAB) and low (LAB) trait anxiety mouse model, Tmem132d was found to show increased expression in the anterior cingulate cortex (aCC) of HAB as compared to LAB mice. To understand the molecular underpinnings underlying the differential expression, we sequenced the gene and found two single-nucleotide polymorphisms (SNPs) in the promoter differing between both lines which could explain the observed mRNA expression profiles using gene reporter assays. In addition, there was no difference in basal DNA methylation in the CpG Island that encompasses the HAB vs. LAB Tmem132d promoter region. Furthermore, we found significantly higher binding of RNA polymerase II (POLR2A) to the proximal HAB-specific SNP (rs233264624) than the corresponding LAB locus in an oligonucleotide pull-down assay, suggesting increased transcription. Virus mediated overexpression of Tmem132d in the aCC of C57BL/6 J mice could confirm its role in mediating an anxiogenic phenotype. To model gene-environmental interactions, HAB mice exposed to enriched environment (HAB-EE) responded with decreased anxiety levels but, had enhanced Tmem132d mRNA expression as compared to standard-housed HAB (HAB-SH) mice. While LAB mice subjected to unpredictable chronic mild stress (LAB-UCMS) exhibited higher anxiety levels and had lower mRNA expression compared to standard-housed LAB (LAB-SH) mice. Chromatin immunoprecipitation revealed significantly higher binding of POLR2A to rs233264624 in HAB-EE, while LAB-UCMS had lower POLR2A binding at this locus, thus explaining the enhanced or attenuated expression of Tmem132d compared to their respective SH controls. To further investigate gene-environment interactions, DNA methylation was assessed using Illumina 450 K BeadChip in 74 panic disorder patients. Significant methylation differences were observed in two CpGs (cg26322591 and cg03283235) located in TMEM132D depending on the number of positive life events supporting the results of an influence of positive environmental cues on regulation of Tmem132d expression in mice.

Local Boards of Health Characteristics Influencing Support for Health Department Accreditation.

BACKGROUND: Local boards of health (LBoHs) serve as the governance body for 71% of local health departments (LHDs). PURPOSE: To assess the impact of LBoH governance functions and other characteristics on the level of LBoH support of LHD accreditation. METHODS: Data from 394 LHDs that participated in the 2015 Local Boards of Health Survey were used for computing summative scores for LBoHs for domains of taxonomy and performing logistic regression analyses in 2016. RESULTS: Increased odds of an LBoH directing, encouraging, or supporting LHD accreditation activities were significantly associated with (a) a higher overall combined score measuring performance of governance functions and presence of other LBoH characteristics (adjusted odds ratio [AOR] = 1.05; P < .001); (b) a higher combined score for the Governance Functions subscale (AOR = 1.06; P < .01); (c) the "continuous improvement" governance function (AOR = 1.15; P < .001); and (d) characteristics and strengths such as board composition (eg, LBoH size, type of training, elected vs nonelected members), community engagement and input, and the absence of an elected official on the board (AOR = 1.14; P = .02). CONCLUSIONS: LBoHs are evenly split by thirds in their attention to Public Health Accreditation Board accreditation among the following categories: (a) encouraged or supported, (b) discussed but made no recommendations, and (c) did not discuss. This split might indicate that they are depending on the professional leadership of the LHD to make the decision or that there is a lack of awareness. The study findings have policy implications for both LBoHs and initiatives aimed at strengthening efforts to promote LHD accreditation.

Creating a Taxonomy of Local Boards of Health Based on Local Health Departments' Perspectives.

OBJECTIVES: To develop a local board of health (LBoH) classification scheme and empirical definitions to provide a coherent framework for describing variation in the LBoHs. METHODS: This study is based on data from the 2015 Local Board of Health Survey, conducted among a nationally representative sample of local health department administrators, with 394 responses. The classification development consisted of the following steps: (1) theoretically guided initial domain development, (2) mapping of the survey variables to the proposed domains, (3) data reduction using principal component analysis and group consensus, and (4) scale development and testing for internal consistency. RESULTS: The final classification scheme included 60 items across 6 governance function domains and an additional domain-LBoH characteristics and strengths, such as meeting frequency, composition, and diversity of information sources. Application of this classification strongly supports the premise that LBoHs differ in their performance of governance functions and in other characteristics. CONCLUSIONS: The LBoH taxonomy provides an empirically tested standardized tool for classifying LBoHs from the viewpoint of local health department administrators. Future studies can use this taxonomy to better characterize the impact of LBoHs.

Provision of Personal Healthcare Services by Local Health Departments: 2008-2013.

INTRODUCTION: The scope of local health department (LHD) involvement in providing personal healthcare services versus population-based services has been debated for decades. A 2012 IOM report suggests that LHDs should gradually withdraw from providing personal healthcare services. The purpose of this study is to assess the level of LHD involvement in provision of personal healthcare services during 2008-2013 and examine the association between provision of personal healthcare services and per capita public health expenditures. METHODS: Data are from the 2013 survey of LHDs and Area Health Resource Files. The number, ratio, and share of revenue from personal healthcare services were estimated. Both linear and panel fixed effects models were used to examine the association between provision of personal healthcare services and per capita public health expenditures. Data were analyzed in 2014. RESULTS: The mean number of personal healthcare services provided by LHDs did not change significantly in 2008-2013. Overall, personal services constituted 28% of total service items. The share of revenue from personal services increased from 16.8% in 2008 to 20.3% in 2013. Results from the fixed effect panel models show a positive association between personal healthcare services' share of revenue and per capita expenditures (b=0.57, p<0.001). CONCLUSIONS: A lower share of revenue from personal healthcare services is associated with lower per capita expenditures. LHDs, especially those serving <25,000 people, are highly dependent on personal healthcare revenue to sustain per capita expenditures. LHDs may need to consider strategies to replace lost revenue from discontinuing provision of personal healthcare services.

Factors driving the adoption of quality improvement initiatives in local health departments: results from the 2010 profile study.

BACKGROUND: Over the past decade, quality improvement (QI) has become a major focus in advancing the goal of improving performance of local health departments (LHDs). However, limited empirical data exists on the current implementation of QI initiatives in LHDs and factors associated with adoption of QI initiatives. OBJECTIVES: (1) To examine the current implementation of QI implementation initiatives by LHDs and (2) to identify factors contributing to LHDs' decision to implement QI initiatives. METHODS: In this study, a novel theoretical framework based on analysis of QI in medicine was applied to analyze QI by LHDs. LHDs' QI adoption was assessed by the number of formal QI projects reported by LHDs that responded to module 1 of the 2010 National Profile of Local Health Department Study (Profile Study) conducted by the National Association of County & City Health Officials. The Profile Study data were merged with data from the Health Resources and Services Administration's Area Resource Files and the Association of State and Territorial Health Officials' 2010 Survey. Logistic regression analyses were conducted using Stata 11 SVY procedure to account for the complex sampling design. RESULTS: The Profile Study data indicated that about 73% of the LHDs reported implementing 1 or more QI projects. LHDs with large jurisdiction population (>50 000), higher per capita public health expenditure, a designated QI staff member, or prior participation in performance improvement programs were more likely to have undertaken QI initiatives. CONCLUSION: According to the Profile Study, more than a quarter of LHDs surveyed did not report implementing any formal QI projects. Greater investments in QI programs and designation of QI staff can be effective strategies to promote QI adoption. The validity of the definition of a formal QI project needs to be established. More research to identify the barriers to successful QI implementation at LHDs is also needed.

Blunted HPA axis reactivity reveals glucocorticoid system dysbalance in a mouse model of high anxiety-related behavior.

Depression and anxiety disorders are often characterized by altered hypothalamic-pituitary-adrenal (HPA) axis re-/activity. However, the presence of a molecular link between dysbalanced neuroendocrine regulation and psychopathologies is not yet fully established. Earlier, we reported that high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice express divergent anxiety-related and passive/active coping phenotypes. Here, we studied mechanisms that might contribute to the different HPA axis reactivity observed in HAB, NAB and LAB mice and their involvement in the regulation of anxiety-related behavior and passive/active coping style. We found that HAB mice respond with significantly reduced corticosterone (CORT) secretion to an acute stressful stimulus and a blunted response in the Dex/CRH test compared to NAB and LAB mice. At the molecular level, higher expression of the glucocorticoid receptor (GR/Nr3c1) and decreased corticotropin-releasing hormone receptor 1 (CRHR1) expression were observed in the pituitary of HAB mice. We further analyzed whether these stress mediators differed between the HAB, NAB and LAB lines in limbic system-associated brain regions and whether their interplay contributes to the phenotype. Interestingly, not only in the pituitary but also in almost all brain regions investigated, GR expression was significantly higher in HAB mice. In contrast, the amount of CORT in the brain structures analyzed was significantly lower in these animals. The expression of CRHR1 varied in the prefrontal cortex only. Since glucocorticoids regulate both GR and CRHR1, we treated HAB and NAB mice chronically with CORT. After 6 weeks of administration, reduced anxiety- and depression-like behaviors were observed in HAB mice, whereas increased anxiety was found in NABs. In both groups, GR, but not CRHR1, were significantly reduced. Taken together, our study proposes HAB mice as an animal model of simultaneous features of increased anxiety-related and depression-like behaviors with blunted HPA axis reactivity suggesting a dysregulated GR/CORT system as one key mechanism behind their phenotype.

Environmental manipulations generate bidirectional shifts in both behavior and gene regulation in a crossbred mouse model of extremes in trait anxiety.

Although gene-environment interactions are known to significantly influence psychopathology-related disease states, only few animal models cover both the genetic background and environmental manipulations. Therefore, we have taken advantage of the bidirectionally inbred high (HAB) and low (LAB) anxiety-related behavior mouse lines to generate HAB × LAB F1 hybrids that intrinsically carry both lines' genetic characteristics, and subsequently raised them in three different environments-standard, enriched (EE) and chronic mild stress (CMS). Assessing genetic correlates of trait anxiety, we focused on two genes already known to play a role in HAB vs. LAB mice, corticotropin releasing hormone receptor type 1 (Crhr1) and high mobility group nucleosomal binding domain 3 (Hmgn3). While EE F1 mice showed decreased anxiety-related and increased explorative behaviors compared to controls, CMS sparked effects in the opposite direction. However, environmental treatments affected the expression of the two genes in distinct ways. Thus, while expression ratios of Hmgn3 between the HAB- and LAB-specific alleles remained equal, total expression resembled the one observed in HAB vs. LAB mice, i.e., decreased after EE and increased after CMS treatment. On the other hand, while total expression of Crhr1 remained unchanged between the groups, the relative expression of HAB- and LAB-specific alleles showed a clear effect following the environmental modifications. Thus, the environmentally driven bidirectional shift of trait anxiety in this F1 model strongly correlated with Hmgn3 expression, irrespective of allele-specific expression patterns that retained the proportions of basic differential HAB vs. LAB expression, making this gene a match for environment-induced modifications. An involvement of Crhr1 in the bidirectional behavioral shift could, however, rather be due to different effects of the HAB- and LAB-specific alleles described here. Both candidate genes therefore deserve attention in the complex regulation of anxiety-related phenotypes including environment-mediated effects.

The relationship between county-level contextual characteristics and use of diabetes care services.

OBJECTIVES: To examine the relationship between county-level measures of social determinants and use of preventive care among US adults with diagnosed diabetes. To inform future diabetes prevention strategies. METHODS: Data are from the Behavioral Risk Factor Surveillance System (BRFSS) 2004 and 2005 surveys, the National Diabetes Surveillance System, and the Area Resource File. Use of diabetes care services was defined by self-reported receipt of 7 preventive care services. Our study sample included 46 806 respondents with self-reported diagnosed diabetes. Multilevel models were run to assess the association between county-level characteristics and receipt of each of the 7 preventive diabetes care service after controlling for characteristics of individuals. Results were considered significant if P < .05. RESULTS: Controlling for individual-level characteristics, our analyses showed that 7 of the 8 county-level factors examined were significantly associated with use of 1 or more preventive diabetes care services. For example, people with diabetes living in a county with a high uninsurance rate were less likely to have an influenza vaccination, visit a doctor for diabetes care, have an A1c test, or a foot examination; people with diabetes living in a county with a high physician density were more likely to have an A1c test, foot examination, or an eye examination; and people with diabetes living in a county with more people with less than high-school education were less likely to have influenza vaccination, pneumococcal vaccination, or self-care education (all P < .05). CONCLUSIONS: Many of the county-level factors examined in this study were found to be significantly associated with use of preventive diabetes care services. County policy makers may need to consider local circumstances to address the disparities in use of these services.

Local health department activities to ensure access to care.

BACKGROUND: Local health departments (LHDs) can play an important role in linking people to personal health services and ensuring the provision of health care when it is otherwise unavailable. However, the extent to which LHDs are involved in ensuring access to health care in its jurisdictions is not well known. PURPOSE: To provide nationally representative estimates of LHD involvement in specific activities to ensure access to healthcare services and to assess their association with macro-environment/community and LHD capacity and process characteristics. METHODS: Data used were from the 2010 National Profile of Local Health Departments Study, Area Resource Files, and the Association of State and Territorial Health Officials' 2010 Profile of State Public Health Agencies Survey. Data were analyzed in 2012. RESULTS: Approximately 66.0% of LHDs conducted activities to ensure access to medical care, 45.9% to dental care, and 32.0% to behavioral health care. About 28% of LHDs had not conducted activities to ensure access to health care in their jurisdictions in 2010. LHDs with higher per capita expenditures and larger jurisdiction population sizes were more likely to provide access to care services (p <0.05). CONCLUSIONS: There is substantial variation in LHD engagement in activities to ensure access to care. Differences in LHD capacity and the needs of the communities in which they are located may account for this variation. Further research is needed to determine whether this variation is associated with adverse population health outcomes.

Real-time imaging of amygdalar network dynamics in vitro reveals a neurophysiological link to behavior in a mouse model of extremes in trait anxiety.

In humans and numerous other mammalian species, individuals considerably vary in their level of trait anxiety. This well known phenomenon is closely related to the etiology of several psychiatric disorders, but its neurophysiological basis remains poorly understood. Here, we applied voltage-sensitive dye imaging to brain slices from animals of the high (HAB), normal (NAB), and low (LAB) trait anxiety mouse model and investigated whether evoked neuronal activity propagations from the lateral (LA) to the central (CeA) amygdala differ in their relative strength among HAB, NAB, and LAB mice. For this purpose, we divided a real-time measure of neuronal population activity in the CeA by a respective measure obtained for the LA. This calculation yielded the metric "CeA/LA activity." Our data clearly demonstrate a positive correlation between trait anxiety levels evaluated by the elevated plus-maze test and CeA/LA activity. Moreover, we found reduced CeA/LA activity in HAB mice, which responded with decreased anxiety levels to an environmental enrichment and, inversely, detected increased anxiety levels and CeA/LA activity in LAB mice that experienced chronic mild stress. We did not observe differences in the spread of neuronal activity in the motor and visual cortex among HAB, NAB, and LAB animals. Collectively, these findings provide evidence that, in mammals, interindividual variability in trait anxiety is causally linked to individual variations in the physiological constitution of the LA-to-CeA circuitry that give rise to a differential regulation of neuronal signal flow through this fundamental input-output network of the amygdala.

Variation in delivery of the 10 essential public health services by local health departments for obesity control in 2005 and 2008.

OBJECTIVES: To describe and compare the capacity of local health departments (LHDs) to perform 10 essential public health services (EPHS) for obesity control in 2005 and 2008, and explore factors associated with provision of these services. METHODS: The data for this study were drawn from the 2005 and 2008 National Profile of Local Health Department surveys, conducted by the National Association of County and City Health Officials. Data were analyzed in SAS version 9.1 (SAS Institute Inc, Cary, North Carolina). RESULTS: The proportion of LHDs that reported that they do not provide any of the EPHS for obesity control decreased from 27.9% in 2005 to 17.0% in 2008. In both 2005 and 2008, the 2 most frequently provided EPHS for obesity control by LHDs were informing, educating, and empowering the people (EPHS 3) and linking people to needed personal health services (EPHS 7). The 2 least frequently provided services were enforcing laws and regulations (EPHS 6) and conducting research (EPHS 10). On average, LHDs provided 3.05 EPHS in 2005 and 3.69 EPHS in 2008. Multiple logistic regression results show that LHDs with larger jurisdiction population, with a local governance, and those that have completed a community health improvement plan were more likely to provide more of the EPHS for obesity (P < .05). CONCLUSIONS: The provision of the 10 EPHS for obesity control by LHDs remains low. Local health departments need more assistance and resources to expand performance of EPHS for obesity control. Future studies are needed to evaluate and promote LHD capacity to deliver evidence-based strategies for obesity control in local communities.

An instrument for assessing public health system performance: validity in rural settings.

PURPOSE: This study evaluated the validity and utility of the Local Public Health System Assessment Instrument (Local Instrument) of the National Public Health Performance Standards Program in rural settings. METHODS: The study compared the Local Instrument scores of 6 rural local public health systems to external assessments of those public health systems. The 6 public health systems represented 3 states in which 1 of the 2 local jurisdictions had scored well below and the other well above the state median in a pilot test of the Local Instrument. The study design featured a case study approach consisting of an iterative and integrated combination of semistructured individual and focus group interviews along with the collection of archival materials provided by the 6 public health systems. FINDINGS: Despite differences in Local Instrument scores, the representative public health systems in each state provided roughly the same levels of public health services. Sites varied tremendously in the percentage of survey items rated highly or less relevant. CONCLUSIONS: The National Public Health Performance Standards Program Local Instrument can provide a useful structure and process for assessing public health system performance at the local level. Key informants provided several recommendations to improve the Local Instrument, including clarification of difficult terminology and acronyms, and development of multiple instruments structured around subsets of survey items.

The business case for preconception care: methods and issues.

Only a limited number of economic evaluations have addressed the costs and benefits of preconception care. In order to persuade health care providers, payers, or purchasers to become actively involved in promoting preconception care, it is important to demonstrate the value of doing so through development of a "business case". Perceived benefits in terms of organizational reputation and market share can be influential in forming a business case. In addition, it is standard to include an economic analysis of financial costs and benefits from the perspective of the provider practice, payer, or purchaser in a business case. The methods, data needs, and other issues involved with preparing an economic analysis of the likely financial return on investment in preconception care are presented here. This is accompanied by a review or case study of economic evaluations of preconception care for women with recognized diabetes. Although the data are not sufficient to draw firm conclusions, there are indications that such care may yield positive financial benefits to health care organizations through reduction in maternal and infant hospitalizations. More work is needed to establish how costs and economic benefits are distributed among different types of organizations. Also, the optimum methods of delivering preconception care for women with diabetes need to be evaluated. Similar assessments should also be conducted for other forms of preconception care, including comprehensive care.

Public health systems research: setting a national agenda.

The Institute of Medicine has recommended that policy decisions about improvement of national public health systems be guided by sound scientific evidence. However, to date there is no national research agenda to help guide public health systems. The Centers for Disease Control and Prevention was called upon to lead a collaborative consensus-based process to define key research questions and establish a framework to create opportunities to better coordinate, leverage, and identify public health resources, which are increasingly scarce. The public health systems research agenda that emerged from this process has 14 over-arching priority research themes. This national agenda should stimulate and guide research to meet the urgent need to improve the nation's public health systems.