Using Plasma Vitellogenin in Loggerhead Sea Turtles to Assess Reproductive Maturation and Estrogen-Like Contaminant Exposure.

Vitellogenin (VTG), an egg yolk precursor, is abnormally produced by male and juvenile oviparous species after exposure to estrogens. Plasma VTG in loggerhead sea turtles (Caretta caretta) helped us understand their reproductive maturation and investigate it as a biomarker of contaminant exposure. The presence of VTG was screened in plasma from 404 loggerheads from the northwestern Atlantic Ocean using a freshwater turtle antibody in western blots. The concentrations of VTG were semiquantified using band intensities calibrated to results from a loggerhead antibody enzyme-linked immunoassay. The detection and concentrations of VTG were in (from highest to lowest): nesting females, in-water adult females, subadult females, smaller females, unknown sex, and males. Loggerheads from this region begin vitellogenesis at ≅77 cm straight carapace length. We classified VTG expression as abnormal in nine male or juvenile turtles. Organochlorine contaminant (OC) concentrations were measured in blood and/or fat biopsies of some turtles. One abnormal VTG female had the second highest fat polychlorinated biphenyl (PCB) and 4,4'-dichlorodiphenyldichloroethylene concentrations compared among 43 VTG-negative juveniles. The nine VTG-abnormal turtles had average blood PCB concentrations 8.5% higher, but not significantly different, than 46 VTG-negative juveniles (p = 0.453). In turtles less than 77 cm, blood PCB concentrations were significantly, but weakly, correlated with semiquantified VTG concentrations (tau = 0.1, p = 0.004). Greater blood OC concentrations were found in adult females than in males, which motivated the creation of a conceptual model of OC, VTG, and hormone concentrations across a reproductive cycle. A decision tree is also provided incorporating VTG as a sexing tool. Abnormal VTG expression cannot conclusively be linked to endocrine disruption caused by these OC concentrations. Studies should further investigate causes of abnormal VTG expression in wild sea turtles. Environ Toxicol Chem 2023;42:1309-1325. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Evaluating Partnerships for Practice Change in the Prevention, Identification, and Treatment of Fetal Alcohol Spectrum Disorders.

Background: In 2014, the Centers for Disease Control and Prevention funded a four-year partnership effort between university and health care professional associations (HCPAs) to reach health care providers (HCPs) nationally in six health disciplines and engage them to adopt evidence-based practices for the prevention, identification, and treatment of fetal alcohol spectrum disorders (FASDs). The aim of this project was to evaluate partnerships for their (1) structure and formation, (2) collaboration process, and (3) outcomes with regard to resources and strategies developed for FASD prevention and management. Methods: We used quantitative and qualitative data from quarterly progress reports, a semi-annual collaboration survey, and annual interviews with each discipline's members. Results: Partnerships in each discipline varied in the number of members and organizations, expertise in the discipline, and access to HCPs. Assigned partnerships with limited researchers' expertise in the discipline or the inability of HCPAs to reach priority audiences created challenges in the development and dissemination of resources. Two partnerships showed challenges in the collaboration process regarding understanding respective responsibilities, sharing similar ideas, and resolving disagreements despite efforts at facilitated discussion. Messaging and resource dissemination by HCPAs and the use of provider champions developed through HCPAs' national network emerged as promising approaches to engage HCPs. Conclusion: Circumstances under which partnerships are formed can facilitate or challenge collaboration and outcome efforts. Discipline-specific partnerships between researchers and HCPAs provide a model for evidence-based resources to be developed and disseminated widely for adoption by HCPs in their practice.

Core procedural skills competencies and the maintenance of procedural skills for medical students: a Delphi study.

BACKGROUND: It is well recognised that medical students need to acquire certain procedural skills during their medical training, however, agreement on the level and acquisition of competency to be achieved in these skills is under debate. Further, the maintenance of competency of procedural skills across medical curricula is often not considered. The purpose of this study was to identify core procedural skills competencies for Australian medical students and to establish the importance of the maintenance of such skills. METHODS: A three-round, online Delphi method was used to identify consensus on competencies of procedural skills for graduating medical students in Australia. In Round 1, an initial structured questionnaire was developed using content identified from the literature. Respondents were thirty-six experts representing medical education and multidisciplinary clinicians involved with medical students undertaking procedural skills, invited to rate their agreement on the inclusion of teaching 74 procedural skills and 11 suggested additional procedures. In Round 2, experts re-appraised the importance of 85 skills and rated the importance of maintenance of competency (i.e., Not at all important to Extremely important). In Round 3, experts rated the level of maintenance of competence (i.e., Observer, Novice, Competent, Proficient) in 46 procedures achieving consensus. RESULTS: Consensus, defined as > 80% agreement, was established with 46 procedural skills across ten categories: cardiovascular, diagnostic/measurement, gastrointestinal, injections/intravenous, ophthalmic/ENT, respiratory, surgical, trauma, women's health and urogenital procedures. The procedural skills that established consensus with the highest level of agreement included cardiopulmonary resuscitation, airway management, asepsis and surgical scrub, gown and gloving. The importance for medical students to demonstrate maintenance of competency in all procedural skills was assessed on the 6-point Likert scale with a mean of 5.03. CONCLUSIONS: The findings from the Delphi study provide critical information about procedural skills for the Clinical Practice domain of Australian medical curricula. The inclusion of experts from medical faculty and clinicians enabled opportunities to capture a range of experience independent of medical speciality. These findings demonstrate the importance of maintenance of competency of procedural skills and provides the groundwork for further investigations into monitoring medical students' skills prior to graduation.

Teaching brief motivational interviewing to medical students using a pedagogical framework.

OBJECTIVE: Medical schools are charged with assisting medical students to acquire the confidence, knowledge and skills for behavior change conversations in primary healthcare. The present study evaluated teaching brief motivational interviewing (MI) to pre-clinical medical students. METHODS: Forty-six students participated in an educational intervention premised on the Learn, See, Practice, Prove, Do, Maintain pedagogical framework, comprising 2 × 2-h lectures, a 2-h role-play triad session, and 3 × 2-h small group simulated patient encounters supported by scaffolding strategies. Measures of brief MI knowledge (MI Knowledge and Attitudes Test & Multiple-Choice Knowledge Test) and confidence (MI Confidence Scale) were taken at baseline, post-training, and 3-month follow-up, and skills (Behavior Change Counseling Index) were assessed at three intervals during simulated patient encounters. RESULTS: Students who received brief MI training improved in knowledge and confidence from baseline to post-training and gains remained at 3-months. Brief MI skills improved across the simulation sessions. CONCLUSION: Pre-clinical medical students can attain knowledge, confidence and skills in brief MI after participation in a short intervention and improvements are sustainable. PRACTICE IMPLICATIONS: Our results support the use of an evidence-based pedagogical framework for teaching brief MI in pre-clinical years of medical curricula and our scaffolding strategy affords promise.

Alcohol Screening and Brief Intervention: Office-Based Primary Care Physicians, U.S., 2015-2016.

INTRODUCTION: In 2013, the U.S. Preventive Services Task Force again recommended alcohol misuse screening and provision of brief behavioral counseling interventions to those engaged in risky drinking for all adults aged ≥18 years in primary care. This report presents national estimates of the provision of alcohol screening and brief intervention by U.S. primary care physicians, the screening methods, and the resources they identified as helpful in implementing alcohol/substance screening and intervention in primary care settings. METHODS: Data included 876 self-identified primary care physicians from the Physician Induction Interview portion of the 2015-2016 National Ambulatory Medical Care Survey, an annual nationally representative sample survey of nonfederal, office-based physicians in the U.S., encompassing all the 50 states and the District of Columbia. Descriptive estimates (annualized percentages) of alcohol misuse screening were generated for selected primary care physician characteristics. Estimates of how primary care physicians reported screening, the frequency of brief intervention, and resources identified as helpful in the implementation of screening/intervention procedures were also generated. Two-tailed significance tests were used to determine the differences between the compared groups. Data analyses were conducted in 2019-2021. RESULTS: In total, 71.7% of office-based primary care physicians reported screening patients for alcohol misuse. Statistically significant differences in screening were observed geographically and by provider specialty. CONCLUSIONS: Less than 40% of primary care physicians who screened patients for alcohol misuse reported always intervening with patients who screened positive for risky alcohol use. Collection of data on resources that primary care physicians report as being helpful for alcohol/substance screening and intervention implementation may be useful in continuous improvement efforts.

CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

[Figure: see text].

Crude Oil and Dispersant Cause Acute Clinicopathological Abnormalities in Hatchling Loggerhead Sea Turtles (Caretta caretta).

Following the explosion of the Deepwater Horizon MC252 oil rig in 2010, 319 live sea turtles exposed to crude oil and oil-dispersant (Corexit) combinations were admitted to rehabilitation centers for decontamination and treatment. Treatment of oiled sea turtles was guided by expected physiological and pathological effects of crude oil exposure extrapolated from studies in other species and from a single loggerhead sea turtle (Caretta caretta) study. While invaluable starting points, inherent limitations to extrapolation, and small sample size of the experimental exposure study, reduce their utility for clinical guidance and for assessing oil spill impacts. Effects of dispersants were not included in the previous experimental exposure study, and cannot be effectively isolated in the analysis of field data from actual spills. A terminal study of pivotal temperature of sex determination using eggs salvaged from doomed loggerhead nests provided an opportunity for an ancillary exposure study to investigate the acute effects of crude oil, dispersant, and a crude oil/dispersant combination in sea turtle hatchlings. Eggs were incubated at 27.2-30.8°C, and hatchlings were randomly assigned to control, oil, dispersant, and combined oil/dispersant exposures for 1 or 4 days. Contaminant exposures were started after a 3 day post-hatching period simulating nest emergence. Turtles were placed in individual glass bowls containing aged seawater and exposed to oil (Gulf Coast-Mixed Crude Oil Sweet, CAS #8002-05-9, 0.833 mL/L) and/or dispersant (Corexit 9500A, 0.083 mL/L), replicating concentrations encountered during oil spills and subsequent response. Statistically significant differences between treatments and non-exposed controls were detected for PCV, AST, uric acid, glucose, calcium, phosphorus, total protein, albumin, globulin, potassium, and sodium. The principal dyscrasias reflected acute osmolar, electrolyte and hydration challenges that were more numerous and greater in combined oil/dispersant exposures at 4 days. Clinicopathological findings were supported by a failure to gain weight (associated with normal hatchling hydration in seawater) in dispersant and combination exposed hatchlings. These findings can help guide clinical response for sea turtles exposed to crude oil and crude oil/dispersant combinations, and indicate potential impacts on wildlife to consider when deploying dispersants in an oil spill response.

NMR Metabolomic Analysis of Skeletal Muscle, Heart, and Liver of Hatchling Loggerhead Sea Turtles (Caretta caretta) Experimentally Exposed to Crude Oil and/or Corexit.

We used nuclear magnetic spectroscopy (NMR) to evaluate the metabolic impacts of crude oil, Corexit 5900A, a dispersant, and a crude oil Corexit 5900A mixture exposure on skeletal muscle, heart, and liver physiology of hatchling loggerhead sea turtles (Caretta caretta). Tissue samples were obtained from 22 seven-day-old hatchlings after a four day cutaneous exposure to environmentally relevant concentrations of crude oil, Corexit 5900A, a combination of crude oil and Corexit 9500A, or a seawater control. We identified 38 metabolites in the aqueous extracts of the liver, and 30 metabolites in both the skeletal and heart muscle aqueous extracts, including organic acids/osmolytes, energy compounds, amino acids, ketone bodies, nucleosides, and nucleotides. Skeletal muscle lactate, creatines, and taurine concentrations were significantly lower in hatchlings exposed to crude oil than in control hatchlings. Lactate, taurine, and cholines appeared to be the basis of some variation in hatchling heart samples, and liver inosine, uracil, and uridine appeared to be influenced by Corexit and crude oil exposure. Observed decreases in concentrations of lactate and creatines may reflect energy depletion in skeletal muscle of oil-exposed animals, while decreased taurine concentrations in these animals may reflect higher oxidative stress.

LRP1 Controls TNF Release via the TIMP-3/ADAM17 Axis in Endotoxin-Activated Macrophages.

The metalloproteinase ADAM17 plays a pivotal role in initiating inflammation by releasing TNF from its precursor. Prolonged TNF release causes many chronic inflammatory diseases, indicating that tight regulation of ADAM17 activity is essential for resolution of inflammation. In this study, we report that the endogenous ADAM17 inhibitor TIMP-3 inhibits ADAM17 activity only when it is bound to the cell surface and that cell surface levels of TIMP-3 in endotoxin-activated human macrophages are dynamically controlled by the endocytic receptor LRP1. Pharmacological blockade of LRP1 inhibited endocytic clearance of TIMP-3, leading to an increase in cell surface levels of the inhibitor that blocked TNF release. Following LPS stimulation, TIMP-3 levels on the surface of macrophages increased 4-fold within 4 h and continued to accumulate at 6 h, before a return to baseline levels at 8 h. This dynamic regulation of cell surface TIMP-3 levels was independent of changes in TIMP-3 mRNA levels, but correlated with shedding of LRP1. These results shed light on the basic mechanisms that maintain a regulated inflammatory response and ensure its timely resolution.

Placental Abnormalities Associated With Childbirth.

Pathologists are faced with a variety of problems when considering placental tissue in cases of stillbirth. It is recognized that there are changes which occur following fetal demise and which can complicate the assessment and may coexist with other morphological changes. It is recognized that up to 25% of stillbirths may have a recognizable abnormality causing fetal demise. A systematic review of placental tissue allows many of these disorders to be identified. This review considers macroscopic and microscopic features of placental pathology in stillbirth together with clinicopathological correlation. Stillbirth definitions, general aspects of macroscopic assessment of placentas, placental changes after fetal demise, and some recognizable causes of fetal demise are considered.

Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity.

Aims: Atherosclerosis is characterized by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Methods and results: Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks. Single-cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE-/- mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell, and innate lymphoid cell (ILC) populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C-), pDC, and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2. Conclusions: A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE-/- mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire toward inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis.

Alcohol Screening and Brief Intervention: A Potential Role in Cancer Prevention for Young Adults.

Excessive or risky alcohol use is a preventable cause of significant morbidity and mortality in the U.S. and worldwide. Alcohol use is a common preventable cancer risk factor among young adults; it is associated with increased risk of developing at least six types of cancer. Alcohol consumed during early adulthood may pose a higher risk of female breast cancer than alcohol consumed later in life. Reducing alcohol use may help prevent cancer. Alcohol misuse screening and brief counseling or intervention (also called alcohol screening and brief intervention among other designations) is known to reduce excessive alcohol use, and the U.S. Preventive Services Task Force recommends that it be implemented for all adults aged ≥18 years in primary healthcare settings. Because the prevalence of excessive alcohol use, particularly binge drinking, peaks among young adults, this time of life may present a unique window of opportunity to talk about the cancer risk associated with alcohol use and how to reduce that risk by reducing excessive drinking or misuse. This article briefly describes alcohol screening and brief intervention, including the Centers for Disease Control and Prevention's recommended approach, and suggests a role for it in the context of cancer prevention. The article also briefly discusses how the Centers for Disease Control and Prevention is working to make alcohol screening and brief intervention a routine element of health care in all primary care settings to identify and help young adults who drink too much.

Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.

BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models. First, atherosclerotic lesion development in hyperlipidemic apolipoprotein E-deficient (ApoE-/-) mice and ApoE-/- mice with a genetic deletion of IRF5 (ApoE-/-Irf5-/-) was compared and then lesion development was assessed in a model of shear stress-modulated vulnerable plaque formation. RESULTS: Both lesion and necrotic core size were significantly reduced in ApoE-/-Irf5-/- mice compared with IRF5-competent ApoE-/- mice. Necrotic core size was also reduced in the model of shear stress-modulated vulnerable plaque formation. A significant loss of CD11c+ macrophages was evident in ApoE-/-Irf5-/- mice in the aorta, draining lymph nodes, and bone marrow cell cultures, indicating that IRF5 maintains CD11c+ macrophages in atherosclerosis. Moreover, we revealed that the CD11c gene is a direct target of IRF5 in macrophages. In the absence of IRF5, CD11c- macrophages displayed a significant increase in expression of the efferocytosis-regulating integrin-ß3 and its ligand milk fat globule-epidermal growth factor 8 protein and enhanced efferocytosis in vitro and in situ. CONCLUSIONS: IRF5 is detrimental in atherosclerosis by promoting the maintenance of proinflammatory CD11c+ macrophages within lesions and controlling the expansion of the necrotic core by impairing efferocytosis.

1H-NMR metabolomic study of whole blood from hatchling loggerhead sea turtles (Caretta caretta) exposed to crude oil and/or Corexit.

We used proton nuclear magnetic resonance spectroscopy (1H-NMR) to evaluate metabolic impacts of environmentally relevant crude oil and Corexit exposures on the physiology of hatchling loggerhead sea turtles (Caretta caretta). Sample extraction and data acquisition methods for very small volume whole blood samples and sources of variation between individual hatchlings were assessed. Sixteen unclotted, whole blood samples were obtained from 7-day-old hatchlings after a 4-day cutaneous exposure to either control seawater, crude oil, Corexit 9500A or a combination of crude oil and Corexit 9500A. After extraction, one- and two-dimensional 1H-NMR spectra of the samples were obtained, and 17 metabolites were identified and confirmed in the whole blood spectra. Variation among samples due to the concentrations of metabolites 3-hydroxybutyrate, lactate, trimethylamine oxide and propylene glycol did not statistically correlate with treatment group. However, the characterization of the hatchling loggerhead whole blood metabolome provides a foundation for future metabolomic research with sea turtles and a basis for the study of tissues from exposed hatchling sea turtles.

Applying positioning theory to examine interactions between simulated patients and medical students: a narrative analysis.

In their journey to becoming doctors, students engage with a range of teachers and trainers. Among these are simulated patients (SPs), who, through role-playing, assist students to develop their communication and physical examination skills, in contexts of formative and summative assessments. This paper explores the teaching and learning relationship between medical students and SPs, and considers how this might affect feedback and assessment. 14 SPs were interviewed on the subject of medical students' professional identity development in 2014. Data were examined using narrative analysis in conjunction with positioning theory to identify the positions that SPs assigned to themselves and to students. Narrative analysis yielded three interpretative positioning themes: Occupational, familial and cultural and discursive and embodied positioning. The interview process revealed that SPs adopt different positions intra-and interpersonally. SPs appear to hold dissonant perceptions of students in terms relating to their emerging professional identities, which may confound assessment and feedback. Training should include reflections on the SP/student relationship to uncover potential biases and positions, giving SPs the opportunity to reflect on and manage their individual and occupational selves.

Vital Signs: Alcohol-Exposed Pregnancies--United States, 2011-2013.

BACKGROUND: Alcohol is a teratogen.* Prenatal alcohol exposure is associated with a range of adverse reproductive outcomes and can cause fetal alcohol spectrum disorders (FASDs) characterized by lifelong physical, behavioral, and intellectual disabilities. FASDs are completely preventable if a woman does not drink alcohol while pregnant. METHODS: CDC analyzed data from the 2011-2013 National Survey of Family Growth to generate U.S. prevalence estimates of risk for an alcohol-exposed pregnancy for 4,303 nonpregnant, nonsterile women aged 15-44 years, by selected demographic and behavioral factors. A woman was considered at risk for an alcohol-exposed pregnancy during the past month if she had sex with a male, drank any alcohol, and did not (and her partner did not with her) use contraception in the past month; was not sterile; and had a partner (or partners) not known to be sterile. RESULTS: The weighted prevalence of alcohol-exposed pregnancy risk among U.S. women aged 15-44 years was 7.3%. During a 1-month period, approximately 3.3 million women in the United States were at risk for an alcohol-exposed pregnancy. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Alcohol use in pregnancy is associated with low birthweight, preterm birth, birth defects, and developmental disabilities. Women of reproductive age should be informed of the risks of alcohol use during pregnancy, and contraception should be recommended, as appropriate, for women who do not want to become pregnant. Women wanting a pregnancy should be advised to stop drinking at the same time contraception is discontinued. Health care providers should advise women not to drink at all if they are pregnant or there is any chance they might be pregnant. Alcohol misuse screening and behavioral counseling (also known as alcohol screening and brief intervention) is recommended for all adults in primary care, including reproductive-aged and pregnant women, as an evidenced-based approach to reducing alcohol consumption among persons who consume alcohol in excess of the recommended guidelines.

Self-Reported Prevalence of Alcohol Screening Among U.S. Adults.

INTRODUCTION: The U.S. Preventive Services Task Force recommends for adults alcohol screening and brief behavioral counseling interventions in primary care settings. However, there is a paucity of population-based data on the prevalence of alcohol screening. This study examines adherence to this U.S. Preventive Services Task Force recommendation by estimating the prevalence of alcohol screening by demographic characteristics and binge drinking. METHODS: A cross-sectional analysis was conducted in 2013 and 2014 on data from the 2013 fall wave of the ConsumerStyles survey. ConsumerStyles is drawn from an Internet panel randomly recruited by probability-based sampling to be representative of the U.S. POPULATION: Data from 2,592 adult respondents who visited primary care physicians in the last year were analyzed to determine the prevalence of alcohol screening. RESULTS: Only 24.7% of respondents reported receiving alcohol screening. The prevalence of screening was similar among women (24.9%) and men (24.5%). Black non-Hispanics reported a significantly lower prevalence of screening than white non-Hispanics (16.2% vs 26.9%, prevalence ratio=0.60, 95% CI=0.40, 0.90). College graduates reported a significantly higher prevalence of screening than respondents with a high school degree or less (28.1% vs 20.8%, prevalence ratio=1.35, 95% CI=1.08, 1.69). CONCLUSIONS: Only about one in four respondents who visited a primary care physician in the last year reported being screened for alcohol misuse. Therefore, many men and women who misuse alcohol are unlikely to be identified. Increased screening may help reduce alcohol misuse and related negative health outcomes.

Indoleamine 2,3-dioxygenase-1 is protective in atherosclerosis and its metabolites provide new opportunities for drug development.

Atherosclerosis is the major cause of cardiovascular disease (CVD), the leading cause of death worldwide. Despite much focus on lipid abnormalities in atherosclerosis, it is clear that the immune system also has important pro- and antiatherogenic functions. The enzyme indoleamine-2,3-dioxygenase (IDO) catalyses degradation of the essential amino acid tryptophan into immunomodulatory metabolites. How IDO deficiency affects immune responses during atherogenesis is unknown and we explored potential mechanisms in models of murine and human atherosclerosis. IDO deficiency in hypercholesterolemic ApoE(-/-) mice caused a significant increase in lesion size and surrogate markers of plaque vulnerability. No significant changes in cholesterol levels were observed but decreases in IL-10 production were found in the peripheral blood, spleen and lymph node B cells of IDO-deficient compared with IDO-competent ApoE(-/-) mice. 3,4,-Dimethoxycinnamoyl anthranilic acid (3,4-DAA), an orally active synthetic derivative of the tryptophan metabolite anthranilic acid, but not l-kynurenine, enhanced production of IL-10 in cultured splenic B cells. Finally, 3,4-DAA treatment reduced lesion formation and inflammation after collar-induced arterial injury in ApoE(-/-) mice, and reduced cytokine and chemokine production in ex vivo human atheroma cell cultures. Our data demonstrate that endogenous production of tryptophan metabolites via IDO is an essential feedback loop that controls atherogenesis and athero-inflammation. We show that the IDO pathway induces production of IL-10 in B cells in vivo and in vitro, suggesting that IDO may induce immunoregulatory functions of B cells in atherosclerosis. The favorable effects of anthranilic acid derivatives in atherosclerosis indicate a novel approach toward therapy of CVD.