Distilling the Fundamentals of Evidence-Based Public Health Policy.

Public health policy interventions are associated with many important public health achievements. To provide public health practitioners and decision makers with practical approaches for examining and employing evidence-based public health (EBPH) policy interventions, we describe the characteristics and benefits that distinguish EBPH policy interventions from programmatic interventions. These characteristics include focusing on health at a population level, focusing on upstream drivers of health, and involving less individual action than programmatic interventions. The benefits of EBPH policy interventions include more sustained effects on health than many programs and an enhanced ability to address health inequities. Early childhood education and universal preschool provide a case example that illustrates the distinction between EBPH policy and programmatic interventions. This review serves as the foundation for 3 concepts that support the effective use of public health policy interventions: applying core component thinking to understand the population health effects of EBPH policy interventions; understanding the influence of existing policies, policy supports, and the context in which a particular policy is implemented on the effectiveness of that policy; and employing a systems thinking approach to identify leverage points where policy implementation can have a meaningful effect.

Advancing Evidence-Based Public Health Policy: How Core Component Thinking Can Illuminate the Multilevel Nature of Public Health Policy.

A growing body of literature uses the concept of core components to better understand small-scale programmatic interventions. Instead of interventions being viewed as unitary "black boxes," interventions are viewed as configurations of core components, which are the parts of interventions that carry their causal potential and therefore need to be reproduced with fidelity to produce the intended effect. To date, the concept of core components has not been as widely applied to public health policy interventions as it has to programmatic interventions. The purpose of this topical review is to familiarize public health practitioners and policy makers with the concept of core components as applied to public health policy interventions. Raising the profile of core component thinking can foster mindful adaptation and implementation of public health policy interventions while encouraging further research to enhance the supporting evidence base. We present 3 types of multilevel interactions in which the core components of a public health policy intervention produce effects at the population level by (1) seeking to directly affect individual behavior, (2) facilitating adoption of programmatic interventions by intermediaries, and (3) encouraging intermediaries to take action that can shape changes in upstream drivers of population health. Changing the unit of analysis from whole policies to core components can provide a basis for understanding how policies work and for facilitating novel evidence-generating strategies and rapid evidence reviews that can inform future adaptation efforts.

A Narrative Review of Literature Examining Studies Researching the Impact of Law on Health and Economic Outcomes.

CONTEXT: Public health policy can play an important role in improving public health outcomes. Accordingly, there has been an increasing emphasis by policy makers on identifying and implementing evidence-informed public health policy interventions. PROGRAM OR POLICY: Growth and refinement of the field of research assessing the impact of legal interventions on health outcomes, known as legal epidemiology, prompted this review of studies on the relationship between laws and health or economic outcomes. IMPLEMENTATION: Authors systematically searched 8 major literature databases for all English language journal articles that assessed the effect of a law on health and economic outcomes published between January 1, 2009, and September 18, 2019. This search generated 12 570 unique articles 177 of which met inclusion criteria. The team conducting the systematic review was a multidisciplinary team that included health economists and public health policy researchers, as well as public health lawyers with expertise in legal epidemiological research methods. The authors identified and assessed the types of methods used to measure the laws' health impact. EVALUATION: In this review, the authors examine how legal epidemiological research methods have been described in the literature as well as trends among the studies. Overall, 3 major themes emerged from this study: (1) limited variability in the sources of the health data across the studies, (2) limited differences in the methodological approaches used to connect law to health outcomes, and (3) lack of transparency surrounding the source and quality of the legal data relied upon. DISCUSSION: Through highlighting public health law research methodologies, this systematic review may inform researchers, practitioners, and lawmakers on how to better examine and understand the impacts of legal interventions on health and economic outcomes. Findings may serve as a source of suggested practices in conducting legal epidemiological outcomes research and identifying conceptual and method-related gaps in the literature.

Domains of Excellence: A CDC Framework for Developing High-Quality, Impact-Driven Public Health Science Publications.

CONTEXT: The Centers for Disease Control and Prevention (CDC) has a long history of using high-quality science to drive public health action that has improved the health, safety, and well-being of people in the United States and globally. To ensure scientific quality, manuscripts authored by CDC staff are required to undergo an internal review and approval process known as clearance. During 2022, CDC launched a scientific clearance transformation initiative to improve the efficiency of the clearance process while ensuring scientific quality. PROGRAM: As part of the scientific clearance transformation initiative, a group of senior scientists across CDC developed a framework called the Domains of Excellence for High-Quality Publications (DOE framework). The framework includes 7 areas ("domains") that authors can consider for developing high-quality and impactful scientific manuscripts: Clarity, Scientific Rigor, Public Health Relevance, Policy Content, Ethical Standards, Collaboration, and Health Equity. Each domain includes multiple quality elements, highlighting specific key considerations within. IMPLEMENTATION: CDC scientists are expected to use the DOE framework when conceptualizing, developing, revising, and reviewing scientific products to support collaboration and to ensure the quality and impact of their scientific manuscripts. DISCUSSION: The DOE framework sets expectations for a consistent standard for scientific manuscripts across CDC and promotes collaboration among authors, partners, and other subject matter experts. Many aspects have broad applicability to the public health field at large and might be relevant for others developing high-quality manuscripts in public health science. The framework can serve as a useful reference document for CDC authors and others in the public health community as they prepare scientific manuscripts for publication and dissemination.

Anti-poverty policy and health: Attributes and diffusion of state earned income tax credits across U.S. states from 1980 to 2020.

PURPOSE: The U.S. federal Earned Income Tax Credit (EITC) is often considered the most effective antipoverty program for families in the U.S., leading to a variety of improved outcomes such as educational attainment, work incentives, economic activity, income, and health benefits for mothers, infants and children. State EITC supplements to the federal credit can significantly enhance the magnitude of this intervention. In this paper we advance EITC and health research by: 1) describing the diffusion of state EITC policies over 40 years, 2) presenting patterns in important EITC policy dimensions across space and time, and 3) disseminating a robust data set to advance future research by policy analysts and scientists. METHODS: We used current public health law research methods to systematically collect, conduct textual legal analysis, and numerically code all EITC legislative changes from 1980 through 2020 in the 50 states and Washington, D.C. RESULTS: First, the pattern of diffusion across states and time shows initial introductions during the 1990s in the Midwest, then spreading to the Northeast, with more recent expansions in the West and South. Second, differences by state and time of important policy dimensions are evident, including size of credit and refundability. Third, state EITC benefits vary considerably by household structure. CONCLUSION: Continued research on health outcomes is warranted to capture the full range of potential beneficial effects of EITCs on family and child wellbeing. Lawyers and policy analysts can collaborate with epidemiologists and economists on other high-quality empirical studies to assess the many dimensions of policy and law that potentially affect the social determinants of health.

Illawarra Born cross-generational health study: feasibility of a multi-generational birth cohort study.

BACKGROUND: There is a strong interest in the concept of developmental origins of health and disease and their influence on various factors "from cradle to grave". Despite the increasing appreciation of this lifelong legacy across the human life course, many gaps remain in the scientific understanding of mechanisms influencing these formative phases. Cross-generational susceptibility to health problems is emerging as a focus of research in the context of birth cohort studies.The primary aim of the Illawarra Born study is to make scientific discoveries associated with improving health and wellbeing across the lifespan, with a particular focus on preventable chronic diseases, especially mental health. This birth cohort study will follow and collect data from three cohorts representing different stages across the lifespan: infants, adults (parents) and older adults (grandparents). The multi-generational, cross-sectional and longitudinal design of this birth cohort study supports a focus on the contributions of genetics, environment and lifestyle on health and wellbeing. The feasibility of conducting a multi-generational longitudinal birth cohort project was conducted through a small pilot study. METHODS/DESIGN: The purpose of this paper is to report on the feasibility and acceptability of the research protocol for a collaborative cross-generation health study in the community and test recruitment and outcome measures for the main study. This feasibility study included pregnant women who were intending to give birth in the Illawarra-Shoalhaven region in Eastern Australia. The area includes a large, regional referral hospital, with capacity to treat specialist and complex cases. Pregnant women were asked to participate in five data collection waves beginning at 22 weeks gestation and ending with a 6-month post-partum appointment. Recruitment was then extended, via the pregnant women, to also include fathers and maternal grandmothers. DISCUSSION: This feasibility study focused on the perinatal period and collected data across three multi-disciplinary domains including mental health, diet, exposures to toxins and the role of these in maternal and infant outcomes. Forty-one families participated in extensive data collection from 22 weeks gestation to 6-months post-partum. Factors impacting on viability and feasibility including recruitment solutions provide the basis for a large-scale study.

Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: A new paradigm for cardiovascular compromise in the preterm newborn.

OBJECTIVE: H2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition. METHODS: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H2 S, was determined by high-performance liquid chromatography. Real-time H2 S production was assessed using a microrespiration system in fetal and postnatal (10, 24 hours) skin and heart samples. CSE contribution was investigated by inhibition via propargylglycine. RESULTS: In preterm animals, postnatal H2 S production capacity in peripheral vasculature increased significantly and was significantly reduced by the inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood flow and capacity of the vasculature to produce H2 S. H2 S produced via CSE did not correlate directly with microvascular blood flow. CONCLUSIONS: In preterm neonates, H2 S production increases during fetal-to-neonatal transition and CSE contribution to total H2 S increases postnatally. CSE-dependent mechanisms may therefore underpin the increase in H2 S production over the first 72 hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability.

Evaluating the Effect of Phosphorylation on the Structure and Dynamics of Hsp27 Dimers by Means of Ion Mobility Mass Spectrometry.

The quaternary structure and dynamics of the human small heat-shock protein Hsp27 are linked to its molecular chaperone function and influenced by post-translational modifications, including phosphorylation. Phosphorylation of Hsp27 promotes oligomer dissociation and can enhance chaperone activity. This study explored the impact of phosphorylation on the quaternary structure and dynamics of Hsp27. Using mutations that mimic phosphorylation, and ion mobility mass spectrometry, we show that successive substitutions result in an increase in the conformational heterogeneity of Hsp27 dimers. In contrast, we did not detect any changes in the structure of an Hsp27 12-mer, representative of larger Hsp27 oligomers. Our data suggest that oligomer dissociation and increased flexibility of the dimer contribute to the enhanced chaperone activity of phosphorylated Hsp27. Thus, post-translational modifications such as phosphorylation play a crucial role in modulating both the tertiary and quaternary structure of Hsp27, which is pivotal to its function as a key component of the proteostasis network in cells. Our data demonstrate the utility of ion mobility mass spectrometry for probing the structure and dynamics of heterogeneous proteins.

The Preschool Activity, Technology, Health, Adiposity, Behaviour and Cognition (PATH-ABC) cohort study: rationale and design.

BACKGROUND: Prevalence estimates internationally suggest that many preschool-aged children (3-5 years) are insufficiently physically active and engage in high levels of screen-based entertainment. Early childhood is the developmental period for which we know the least about the effects of physical activity on development and health. Likewise, rapid technological advancements in mobile electronic media have made screen-based forms of entertainment for young children ubiquitous, and research demonstrating the impacts on cognition, psychosocial well-being, and health has lagged behind the rate of adoption of these technologies. The purpose of the Preschool Activity, Technology, Health, Adiposity, Behaviour and Cognition (PATH-ABC) study is to investigate if physical activity and screen-based entertainment are independently associated with cognitive and psychosocial development, and health outcomes in young children, and if so, how much and which types of these behaviours might be most influential. METHODS: The PATH-ABC study is a prospective cohort, aiming to recruit 430 3-5 year-old children. Children are recruited through and complete initial assessments at their Early Childhood Education and Care (ECEC) centre, and then 12-months later at their centre or school. Direct assessments are made of children's habitual physical activity using accelerometry, cognitive (executive function) and language development (expressive vocabulary), psychosocial development (emotional understanding, Theory of Mind, empathy, and heart rate variability), adiposity (body mass index and waist circumference), and cardiovascular health (blood pressure and retinal micro- vasculature). Educators report on children's psychological strengths and difficulties and self-regulation. Parents report on children's habitual use of electronic media and other child, parent and household characteristics. DISCUSSION: The PATH-ABC study aims to provide evidence to enhance understanding of how much and which types of physical activity and screen-based media influence development and health in preschool-aged children. This information would benefit parents, educators, health professionals and governments seeking to develop strategies and policies to give young children the best start in life by promoting healthy levels of physical activity and electronic media use.

Interactions of the gasotransmitters contribute to microvascular tone (dys)regulation in the preterm neonate.

BACKGROUND & AIMS: Hydrogen sulphide (H2S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow. METHODS: 90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions. RESULTS: No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented. CONCLUSIONS: The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.

Phosphomimics destabilize Hsp27 oligomeric assemblies and enhance chaperone activity.

Serine phosphorylation of the mammalian small heat-shock protein Hsp27 at residues 15, 78, and 82 is thought to regulate its structure and chaperone function; however, the site-specific impact has not been established. We used mass spectrometry to assess the combinatorial effect of mutations that mimic phosphorylation upon the oligomeric state of Hsp27. Comprehensive dimerization yielded a relatively uncrowded spectrum, composed solely of even-sized oligomers. Modification at one or two serines decreased the average oligomeric size, while the triple mutant was predominantly a dimer. These changes were reflected in a greater propensity for oligomers to dissociate upon increased modification. The ability of Hsp27 to prevent amorphous or fibrillar aggregation of target proteins was enhanced and correlated with the amount of dissociated species present. We propose that, in vivo, phosphorylation promotes oligomer dissociation, thereby enhancing chaperone activity. Our data support a model in which dimers are the chaperone-active component of Hsp27.

Diet fatty acid profile, membrane composition and lifespan: an experimental study using the blowfly (Calliphora stygia).

The membrane pacemaker theory of ageing proposes that the polyunsaturated fatty acid (PUFA) composition of membrane lipids of a species is an important determinant of its maximum lifespan. We report three experiments using the blowfly Calliphora stygia, where this theory was tested by manipulation of dietary fat profile. Although the fat profile of the larval diet resulted in small alterations of individual membrane fatty acids, it had no effect on the peroxidation index (PI) of membrane lipids and furthermore had no effect on maximum lifespan. Similarly, manipulation of the fat profile of the adult diet resulted in small changes in individual fatty acids, but had no effect on the PI of membrane lipids. There was a small increase in maximum lifespan when adult diet was supplemented with PUFA in form of vegetable oils but no effect when diet was supplemented with pure PUFA. This difference is possibly due to antioxidant content of vegetable oils. The relative refractoriness of membrane PI to dramatic changes in response to diet is similar to the situation in the rat. These results also indicate the blowfly is unable to convert 18-carbon PUFA to more highly polyunsaturated 20- and 22-carbon PUFA.

Polyunsaturated fats, membrane lipids and animal longevity.

Fatty acids are essential for life because they are essential components of cellular membranes. Lower animals can synthesize all four classes of fatty acids from non-lipid sources, but both omega-6 and omega-3 cannot be synthesized de novo by 'higher' animals and are therefore essential components of their diet. The relationship between normal variation in diet fatty acid composition and membrane fatty acid composition is little investigated. Studies in the rat show that, with respect to the general classes of fatty acids (saturated, monounsaturated and polyunsaturated) membrane fatty acid composition is homeostatically regulated despite diet variation. This is not the case for fatty acid composition of storage lipids, which responds to diet variation. Polyunsaturated fatty acids are important determinants of physical and chemical properties of membranes. They are the substrates for lipid peroxidation and it is possible to calculate a peroxidation index (PI) for a particular membrane composition. Membrane PI appears to be homeostatically regulated with respect to diet PI. Membrane fatty acid composition varies among species and membrane PI is inversely correlated to longevity in mammals, birds, bivalve molluscs, honeybees and the nematode Caenorhabditis elegans.

Effect of temperature on the rate of ageing: an experimental study of the blowfly Calliphora stygia.

All organisms age, the rate of which can be measured by demographic analysis of mortality rates. The rate of ageing is thermally sensitive in ectothermic invertebrates and we examined the effects of temperature on both demographic rates of ageing and on cellular senescence in the blowfly, Calliphora stygia. The short lifespan of these flies is advantageous for demographic measurements while their large body size permits individual-based biochemical characterisation. Blowflies maintained at temperatures from 12°C to 34°C had a five to six-fold decrease in maximum and average longevity, respectively. Mortality rates were best described by a two-phase Gompertz relation, which revealed the first-phase of ageing to be much more temperature sensitive than the second stage. Flies held at low temperatures had both a slower first-phase rate of ageing and a delayed onset of second-phase ageing, which significantly extended their longevity compared with those at high temperatures. Blowflies that were transferred from 29°C to 15°C had higher first-phase mortality rates than those of flies held at constant 15°C, but their onset of second-phase ageing was deferred beyond that of flies held constantly at this temperature. The accumulation of fluorescent AGE pigment, a measure of cellular oxidative damage, increased steadily over time in all blowflies, irrespective of the temporal pattern of mortality. Pigment accumulated steadily during periods of 'negligible senescence', as measured by minimal rate of mortality, and the rate of accumulation was significantly affected by temperature. Thus accumulation of AGE pigment is more representative of chronological age than a reflection of biological age or a cause of mortality.