Systemic considerations with pigmented fundus lesions and retinal pigment epithelium hamartomas in Turcot syndrome.

PURPOSE OF REVIEW: To illustrate retinal pigment epithelium hamartomas (RPEHs) in a patient with known Turcot syndrome and to demonstrate the significance of these lesions in other colonic polyposis syndromes. RECENT FINDINGS: The presence of multiple, bilateral RPEHs is a specific marker for familial adenomatous polyposis (FAP). Recent studies have noted RPEHs in associated syndromes including Gardner and Turcot syndromes. Herein, we illustrate an 18-year-old male patient with known brain medulloblastoma who was documented 7 years later to have asymptomatic RPEHs in both eyes, demonstrating hypo-autofluorescence. SUMMARY: This patient with previous medulloblastoma and known Turcot syndrome was later found to have typical RPEHs, a feature that is important in family screening. Confirmation of RPEHs related to Turcot syndrome was made, and genetic evaluation confirmed germline mutation in the adenomatous polyposis coli (APC) gene. Observation was advised. Due to the fairly rapid progression to colorectal cancer if untreated, ophthalmologists should be aware that RPEHs can be the first extracolonic manifestation of FAP, Gardner syndrome, and Turcot syndrome.

Broader perspective on ecosystem sustainability: consequences for decision making.

Although the concept of ecosystem sustainability has a long-term focus, it is often viewed from a static system perspective. Because most ecosystems are dynamic, we explore sustainability assessments from three additional perspectives: resilient systems; systems where tipping points occur; and systems subject to episodic resetting. Whereas foundations of ecosystem resilience originated in ecology, recent discussions have focused on geophysical attributes, and it is recognized that dynamic system components may not return to their former state following perturbations. Tipping points emerge when chronic changes (typically anthropogenic, but sometimes natural) push ecosystems to thresholds that cause collapse of process and function and may become permanent. Ecosystem resetting occurs when episodic natural disasters breach thresholds with little or no warning, resulting in long-term changes to environmental attributes or ecosystem function. An example of sustainability assessment of ecosystem goods and services along the Gulf Coast (USA) demonstrates the need to include both the resilient and dynamic nature of biogeomorphic components. Mountain road development in northwest Yunnan, China, makes rivers and related habitat vulnerable to tipping points. Ecosystems reset by natural disasters are also presented, emphasizing the need to understand the magnitude frequency and interrelationships among major disturbances, as shown by (i) the 2011 Great East Japan Earthquake and resulting tsunami, including how unsustainable urban development exacerbates geodisaster propagation, and (ii) repeated major earthquakes and associated geomorphic and vegetation disturbances in Papua New Guinea. Although all of these ecosystem perturbations and shifts are individually recognized, they are not embraced in contemporary sustainable decision making.

Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice.

G protein-coupled receptor 119 (GPR119) is a G protein-coupled receptor expressed predominantly in pancreatic ß-cells and gastrointestinal enteroendocrine cells. Metformin is a first-line treatment of type 2 diabetes, with minimal weight loss in humans. In this study, we investigated the effects of GSK2041706 [2-([(1S)-1-(1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl)ethyl]oxy)-5-[4-(methylsulfonyl)phenyl]pyrazine], a GPR119 agonist, and metformin as monotherapy or in combination on body weight in a diet-induced obese (DIO) mouse model. Relative to vehicle controls, 14-day treatment with GSK2041706 (30 mg/kg b.i.d.) or metformin at 30 and 100 mg/kg b.i.d. alone caused a 7.4%, 3.5%, and 4.4% (all P < 0.05) weight loss, respectively. The combination of GSK2041706 with metformin at 30 or 100 mg/kg resulted in a 9.5% and 16.7% weight loss, respectively. The combination of GSK2041706 and metformin at 100 mg/kg caused a significantly greater weight loss than the projected additive weight loss of 11.8%. This body weight effect was predominantly due to a loss of fat. Cumulative food intake was reduced by 17.1% with GSK2041706 alone and 6.6% and 8.7% with metformin at 30 and 100 mg/kg, respectively. The combination of GSK2041706 with metformin caused greater reductions in cumulative food intake (22.2% at 30 mg/kg and 37.5% at 100 mg/kg) and higher fed plasma glucagon-like peptide 1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels compared with their monotherapy groups. In addition, we characterized the effect of GSK2041706 and metformin as monotherapy or in combination on neuronal activation in the appetite regulating centers in fasted DIO mice. In conclusion, our data demonstrate the beneficial effects of combining a GPR119 agonist with metformin in the regulation of body weight in DIO mice.

Polling places, pharmacies, and public health: Vote & Vax 2012.

US national elections, which draw sizable numbers of older voters, take place during flu-shot season and represent an untapped opportunity for large-scale delivery of vaccinations. In 2012, Vote & Vax deployed a total of 1585 clinics in 48 states; Washington, DC; Guam; Puerto Rico; and the US Virgin Islands. Approximately 934 clinics were located in pharmacies, and 651 were near polling places. Polling place clinics delivered significantly more vaccines than did pharmacies (5710 vs 3669). The delivery of vaccines was estimated at 9379, and approximately 45% of the recipients identified their race/ethnicity as African American or Hispanic. More than half of the White Vote & Vax recipients and more than two thirds of the non-White recipients were not regular flu shot recipients.

Strategic priorities to increase use of clinical preventive services among older US adults.

The objective of this project was to obtain professionals' perceptions of system-level strategies with potential to increase use of clinical preventive services (CPS) among adults aged 50 years or older through community settings. Public health, aging services, and medical professionals participated in guided discussions and a modified Delphi process. Priority strategies, determined on the basis of a 70% or higher a priori agreement level, included enhancing community capacity; promoting the design of health information technologies to exchange data between clinical and community settings; promoting care coordination; broadening scope of practice; providing incentives to employers; and eliminating cost-sharing. Findings provide insights about preferences for system-level strategies that align with national and state initiatives to increase CPS use.

Clinical predictors of the optimal spectacle correction for comfort performing desktop tasks.

BACKGROUND: The best strategy for spectacle correction of presbyopia for near tasks has not been determined. METHODS: Thirty volunteers over the age of 40 years were tested for subjective accommodative amplitude, pupillary size, fusional vergence, interpupillary distance, arm length, preferred working distance, near and far visual acuity and preferred reading correction in the phoropter and trial frames. Subjects performed near tasks (reading, writing and counting change) using various spectacle correction strengths. Predictors of the correction maximising near task comfort were determined by multivariable linear regression. RESULTS: The mean age was 54.9 years (range 43 to 71) and 40 per cent had diabetes. Significant predictors of the most comfortable addition in univariate analyses were age (p<0.001), interpupillary distance (p=0.02), fusional vergence amplitude (p=0.02), distance visual acuity in the worse eye (p=0.01), vision at 40 cm in the worse eye with distance correction (p=0.01), duration of diabetes (p=0.01), and the preferred correction to read at 40 cm with the phoropter (p=0.002) or trial frames (p<0.001). Target distance selected wearing trial frames (in dioptres), arm length, and accommodative amplitude were not significant predictors (p>0.15). The preferred addition wearing trial frames holding a reading target at a distance selected by the patient was the only independent predictor. Excluding this variable, distance visual acuity was predictive independent of age or near vision wearing distance correction. The distance selected for task performance was predicted by vision wearing distance correction at near and at distance. CONCLUSIONS: Multivariable linear regression can be used to generate tables based on distance visual acuity and age or near vision wearing distance correction to determine tentative near spectacle addition. Final spectacle correction for desktop tasks can be estimated by subjective refraction with trial frames.

Expanding the delivery of clinical preventive services through community collaboration: the SPARC model.

BACKGROUND: Population-based rates of adult vaccinations and cancer screenings are low, with less than 40% of older adults up to date with routinely recommended prevention services. Delivery rates are lower still in poor and minority communities. CONTEXT: During the past 10 years, Sickness Prevention Achieved through Regional Collaboration (SPARC), a New England-based nonprofit agency, has developed a promising model for increasing community-wide delivery of prevention services. However, the SPARC model has not been tested in communities elsewhere. In 2006, the Centers for Disease Control and Prevention facilitated a partnership between SPARC and the Aging Services division of the Atlanta Regional Commission to evaluate the program's replicability. METHODS: SPARC coalitions involving local public health agencies, hospitals, social service organizations, and advocacy groups were established in two counties of the region, with the Atlanta Regional Commission providing regional coordination. Using the SPARC model, the coalitions planned, marketed, and implemented community-based activities to deliver adult screenings and vaccinations. CONSEQUENCES: During a 3-week pilot phase, SPARC clinics were held in central Atlanta at three senior housing facilities, a local fire station, and a charter middle school, delivering 353 prevention services to 314 residents. In Fayette County, 634 people received influenza vaccinations on Election Day at SPARC clinics located near 10 polling places. INTERPRETATION: The SPARC model provides a practical framework for improving the community-wide delivery of disease prevention services. The model can galvanize local health services providers to develop successful locally tailored interventions, and the approach is applicable in communities outside of SPARC's home region.

Disaster preparedness and the chronic disease needs of vulnerable older adults.

About 80% of older adults have at least one chronic condition that makes them more vulnerable than healthy people during a disaster. These chronic conditions - combined with the physiological, sensory, and cognitive changes experienced as part of aging - result in frail older adults having special needs during emergencies. Planning and coordination among public health and emergency preparedness professionals and professionals who provide services for the aging are essential to meet these special needs. Several tools and strategies already exist to help prepare these professionals to protect and assist older adults during a disaster. These include having professionals from diverse fields work and train in coalitions, ensuring that advocates for older adults participate in community-wide emergency preparedness, and using community mapping data to identify areas where many older adults live.

Representing causal knowledge in environmental policy interventions: Advantages and opportunities for qualitative influence diagram applications.

This article develops and explores a methodology for using qualitative influence diagrams in environmental policy and management to support decision-making efforts that minimize risk and increase resiliency. Influence diagrams are representations of the conditional aspects of a problem domain. Their graphical properties are useful for structuring causal knowledge relevant to policy interventions and can be used to enhance inference and inclusivity of multiple viewpoints. Qualitative components of influence diagrams are beneficial tools for identifying and examining the interactions among the critical variables in complex policy development and implementation. Policy interventions on social-environmental systems can be intuitively diagrammed for representing knowledge of critical relationships among economic, environmental, and social attributes. Examples relevant to coastal resiliency issues in the US Gulf Coast region are developed to illustrate model structures for developing qualitative influence diagrams useful for clarifying important policy intervention issues and enhancing transparency in decision making. Integr Environ Assess Manag 2018;14:381-394. Published 2018. This article is a US Government work and is in the public domain in the USA.

Representing causal knowledge in environmental policy interventions: Advantages and opportunities for qualitative influence diagram applications.

This article develops and explores a methodology for using qualitative influence diagrams in environmental policy and management to support decision making efforts that minimize risk and increase resiliency. Influence diagrams are representations of the conditional aspects of a problem domain. Their graphical properties are useful for structuring causal knowledge relevant to policy interventions and can be used to enhance inference and inclusivity of multiple viewpoints. Qualitative components of influence diagrams are beneficial tools for identifying and examining the interactions among the critical variables in complex policy development and implementation. Policy interventions on social-environmental systems can be intuitively diagrammed for representing knowledge of critical relationships among economic, environmental, and social attributes. Examples relevant to coastal resiliency issues in the U.S. Gulf Coast region are developed to illustrate model structures for developing qualitative influence diagrams useful for clarifying important policy intervention issues and enhancing transparency in decision making. This article is protected by copyright. All rights reserved.

Tumor-immune profiling of murine syngeneic tumor models as a framework to guide mechanistic studies and predict therapy response in distinct tumor microenvironments.

Mouse syngeneic tumor models are widely used tools to demonstrate activity of novel anti-cancer immunotherapies. Despite their widespread use, a comprehensive view of their tumor-immune compositions and their relevance to human tumors has only begun to emerge. We propose each model possesses a unique tumor-immune infiltrate profile that can be probed with immunotherapies to inform on anti-tumor mechanisms and treatment strategies in human tumors with similar profiles. In support of this endeavor, we characterized the tumor microenvironment of four commonly used models and demonstrate they encompass a range of immunogenicities, from highly immune infiltrated RENCA tumors to poorly infiltrated B16F10 tumors. Tumor cell lines for each model exhibit different intrinsic factors in vitro that likely influence immune infiltration upon subcutaneous implantation. Similarly, solid tumors in vivo for each model are unique, each enriched in distinct features ranging from pathogen response elements to antigen presentation machinery. As RENCA tumors progress in size, all major T cell populations diminish while myeloid-derived suppressor cells become more enriched, possibly driving immune suppression and tumor progression. In CT26 tumors, CD8 T cells paradoxically increase in density yet are restrained as tumor volume increases. Finally, immunotherapy treatment across these different tumor-immune landscapes segregate into responders and non-responders based on features partially dependent on pre-existing immune infiltrates. Overall, these studies provide an important resource to enhance our translation of syngeneic models to human tumors. Future mechanistic studies paired with this resource will help identify responsive patient populations and improve strategies where immunotherapies are predicted to be ineffective.

U.S. Environmental Protection Agency's activities to prepare for regulatory and risk assessment applications of genomics information.

Genomics is expected to have significant implications for risk assessment and regulatory decision making. Since 2002, the U.S. Environmental Protection Agency (EPA) has undertaken a number of cross-agency activities to further prepare itself to receive, interpret, and apply genomics information for risk assessment and regulatory purposes. These activities include: (1) the issuance of an Interim Genomics Policy on the use of genomics information in risk assessments and decision making, (2) the release of the 2004 Genomics White Paper, which outlines potential applications and implications of genomics for EPA, and (3) the recent release of the external review draft of the Interim Guidance on Microarray-Based Assays, which outlines data submission, quality, analysis, management, and training considerations for such data. This manuscript discusses these activities and more recent follow-up activities with the aim of further communicating these efforts to the broader scientific and stakeholder community.

One health-Transdisciplinary opportunities for SETAC leadership in integrating and improving the health of people, animals, and the environment.

One Health is a collaborative, transdisciplinary effort working locally, nationally, and globally to improve health for people, animals, plants, and the environment. The term is relatively new (from ∼2003), and it is increasingly common to see One Health included by name in interinstitutional research partnerships, conferences, communications, and organizational frameworks, particularly those championed by the human health and veterinary medical communities. Environmental quality is arguably the least developed component within the One Health framework, but can be guided by expertise within the Society of Environmental Toxicology and Chemistry (SETAC). Despite SETAC's long history of tripartite (academic, government, business) interdisciplinary environmental science activities, the term "One Health" is seldom used in SETAC communications (i.e., many of SETAC's activities are guided by One Health, but it is called by other names in SETAC's journals, newsletters, and presentations). Accordingly, the objective of this Focus article is to introduce the One Health concept to the SETAC membership. The article discusses the origins, evolution, and utility of the One Health approach as an organizational framework and provides key examples of ways in which SETAC expertise can benefit the One Health community. The authors assert that One Health needs SETAC and, to be most effective, SETAC needs One Health. Given that One Health to date has focused too little on the environment, on ecosystems, and on contaminants, SETAC's constructive involvement in One Health presents an opportunity to accelerate actions that will ultimately better protect human and ecosystem health. Environ Toxicol Chem 2016;35:2383-2391. © 2016 SETAC.

Aging and public health: partnerships that can affect cardiovascular health programs.

Cardiovascular health programs face a growing and not often recognized challenge--the aging of the American population. During this century, all states will experience a dramatic rise in the number of older adults. By 2030, approximately 20% of Americans will be over the age of 65. This article describes the prevalence of cardiovascular disease among older adults, the public health and aging services networks, selected results and recommendations from the Aging States Project, and examples of ongoing aging activities relevant to cardiovascular health programs being promoted by the U.S. Centers for Disease Control and Prevention (CDC). State health departments (SHDs) and state units on aging (SUAs) bring different resources, approaches, and partners to address older adult health but many aspects are complementary. The aging services network is extensive, and in one form or another, can reach older adults in virtually every community in the country. Based on a survey of SHDs and SUAs, which was part of the Aging States Project, respondents identified cardiovascular disease as the most common health concern (57% of SHDs and 55% of SUAs). However, fewer than half of those responding reported having cardiovascular health programs directed at older adults (37% of SHDs and 40% of SUAs). Initial activities are described in the arenas of strategic partnerships, data for action, and capacity building based on recommendations from the survey findings. These examples are provided as potential models for current and future state cardiovascular health programs wanting to enhance their reach to older adults.

Bone from an orbital floor fracture causing an intraocular foreign body.

PURPOSE: To describe the ophthalmoscopic and radiologic findings of a patient who sustained blunt orbital trauma. A piece of bone from the fractured orbital wall caused an intraocular foreign body. DESIGN: Case report. METHODS: An 18-year-old man underwent full ophthalmoscopic examination 1 week after sustaining blunt ocular trauma to the right eye while playing basketball. B-scan ultrasonography and computed tomography of the orbits were also performed. RESULTS: Visual acuity, intraocular pressure, and anterior segment examination were normal. Funduscopic examination revealed a fragment of bone that had penetrated the sclera, choroid, and retina. A hole in the sclera was visible. No treatment was performed. Three months later, the patient had no ocular complaints or complications as a result of this injury. CONCLUSION: Bone from a patient's orbit may cause an intraocular foreign body that may be followed conservatively in certain circumstances.

Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system.

The nuclear oxysterol receptors liver X receptor-alpha [LXRalpha (NR1H3)] and LXRbeta (NR1H2) coordinately regulate genes involved in cholesterol homeostasis. Although both LXR subtypes are expressed in the brain, their roles in this tissue remain largely unexplored. In this report, we show that LXR agonists have marked effects on gene expression in murine brain tissue both in vitro and in vivo. In primary astrocyte cultures, LXR agonists regulated several established LXR target genes, including ATP binding cassette transporter A1, and enhanced cholesterol efflux. In contrast, little or no effect on gene expression or cholesterol efflux was detected in primary neuronal cultures. Treatment of mice with a selective LXR agonist resulted in the induction of several LXR target genes related to cholesterol homeostasis in the cerebellum and hippocampus. These data provide the first evidence that the LXRs regulate cholesterol homeostasis in the central nervous system. Because dysregulation of cholesterol balance is implicated in central nervous system diseases such as Alzheimer's and Niemann-Pick disease, pharmacological manipulation of the LXRs may prove beneficial in the treatment of these disorders.

Relationship between ethinylestradiol-mediated changes in endocrine function and reproductive impairment in Japanese medaka (Oryzias latipes).

Many biochemical endpoints currently are used to describe endocrine function in fish; however, the sensitivity of these parameters as biomarkers of impaired reproduction or sexual development is not well understood. In the present study, adult Japanese medaka (Oryzias latipes) were assessed for reproductive output and endocrine function, including circulating steroid concentrations, ex vivo steroidogenesis from the gonads, aromatase activity, hepatic estrogen receptor (ER), and plasma vitellogenin (VTG) after exposure to 0, 0.2, 5, 500, and 2,000 ng/L of 17alpha-ethinylestradiol (EE) for 14 d. The EE altered these biochemical responses at various sites along the hypothalamus-pituitary-gonadal axis at concentrations as low as 0.2 ng/L, but it only depressed reproductive function at concentrations of 500 ng/L or greater. Offspring also had reduced ability to hatch at 500 ng/L of EE, but this concentration did not produce any other observed changes in development or sexual phenotype. The reproductive parameters correlated well with VTG, ER, and gonadosomatic index (GSI) in both sexes of adult medaka, which could be indicative of the ER-mediated mode of action for EE. Vitellogenin and ER were elevated at higher concentrations of EE in both sexes, whereas GSI was decreased. Overall, most biochemical endpoints were more sensitive than reproduction or development to exposure, indicating that reproductive function may be relatively protected.

Infrared imaging enhances retinal crystals in Bietti's crystalline dystrophy.

Infrared imaging dramatically increased the number of crystalline deposits visualized compared with clinical examination, standard color fundus photography, and red free imaging in patients with Bietti's crystalline dystrophy. We believe that this imaging modality significantly improves the sensitivity with which these lesions are detected, facilitating earlier diagnosis and may potentially serve as a prognostic indicator when examined over time.

Sustainable watersheds: integrating ecosystem services and public health.

Sustainable management of aquatic ecosystems is a worldwide priority; the integrity of these systems depends, in turn, on the integrity of the watersheds (catchments) in which they are embedded. In this article, we present the concepts, background, and scientific foundations for assessing, both nationally and at finer scales, the relationships between ecosystem services, human health, and socioeconomic values in the context of water quality, water quantity, landscapes, the condition of watersheds, and the connectivity of waters, from headwaters to estuaries and the coastal ocean. These assessments will be a foundation for what we have termed "watershed epidemiology," through which the connections between ecosystems and human health can be explored over broad spatial and temporal scales. Understanding and communicating these relationships should lead to greater awareness of the roles watersheds play in human well-being, and hence to better management and stewardship of water resources. The U.S. Environmental Protection Agency is developing the research, models, and planning tools to support operational national assessments of watershed sustainability, building upon ongoing assessments of aquatic resources in streams, rivers, lakes, wetlands and estuaries.

Mental health disorders among an invisible minority: depression and dementia among american Indian and alaska native elders.

According to the 2010 Census, 5.2 million people identified themselves as American Indian or Alaska Native (AIAN) in the United States. This was an increase of 39% from the prior Census, making AIANs one of the nation's fastest growing populations. The health and social programs reaching them, however, have experienced documented devastating shortfalls. Decades of inadequate resources have resulted in significant health and socioeconomic disparities. AIANs are often considered an "invisible minority." In 2012, there were 266,000 AIAN elders 65 or older who claimed one race alone. That number is projected to almost triple by 2030-when the nation's baby boomers move into the ranks of the older population. This article provides an overview of two primary mental health issues-depression and dementia-that will confront this emerging AIAN elder population. Although other health and social issues exist, this article addresses depression and dementia because they are hidden from the community and from health care agencies. This paper focuses both on the unique characteristics of the AIAN population and why it is important to address depression and dementia. The conclusion explores pragmatic policy recommendations for improving the health and long-term mental health care status of AIAN elders.