Publications by authors named "C Herbert Pratt"

940 Publications

Integration of genomic sequencing into the response to the Ebola virus outbreak in Nord Kivu, Democratic Republic of the Congo.

Nat Med 2021 Apr 12. Epub 2021 Apr 12.

Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

On 1 August 2018, the Democratic Republic of the Congo (DRC) declared its tenth Ebola virus disease (EVD) outbreak. To aid the epidemiologic response, the Institut National de Recherche Biomédicale (INRB) implemented an end-to-end genomic surveillance system, including sequencing, bioinformatic analysis and dissemination of genomic epidemiologic results to frontline public health workers. We report 744 new genomes sampled between 27 July 2018 and 27 April 2020 generated by this surveillance effort. Together with previously available sequence data (n = 48 genomes), these data represent almost 24% of all laboratory-confirmed Ebola virus (EBOV) infections in DRC in the period analyzed. We inferred spatiotemporal transmission dynamics from the genomic data as new sequences were generated, and disseminated the results to support epidemiologic response efforts. Here we provide an overview of how this genomic surveillance system functioned, present a full phylodynamic analysis of 792 Ebola genomes from the Nord Kivu outbreak and discuss how the genomic surveillance data informed response efforts and public health decision making.
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http://dx.doi.org/10.1038/s41591-021-01302-zDOI Listing
April 2021

Genome Analysis for Sequence Variants in SARS-CoV-2 Among Asymptomatic Individuals in a Long-term Care Facility.

JAMA Netw Open 2021 04 1;4(4):e217939. Epub 2021 Apr 1.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.7939DOI Listing
April 2021

Use of Stay-at-Home Orders and Mask Mandates to Control COVID-19 Transmission - Blackfeet Tribal Reservation, Montana, June-December 2020.

MMWR Morb Mortal Wkly Rep 2021 Apr 9;70(14):514-518. Epub 2021 Apr 9.

COVID-19 has disproportionately affected persons who identify as non-Hispanic American Indian or Alaska Native (AI/AN) (1). The Blackfeet Tribal Reservation, the northern Montana home of the sovereign Blackfeet Nation, with an estimated population of 10,629 (2), detected the first COVID-19 case in the community on June 16, 2020. Following CDC guidance,* and with free testing widely available, the Indian Health Service and Blackfeet Tribal Health Department began investigating all confirmed cases and their contacts on June 25. The relationship between three community mitigation resolutions passed and enforced by the Blackfeet Tribal Business Council and changes in the daily COVID-19 incidence and in the distributions of new cases was assessed. After the September 28 issuance of a strictly enforced stay-at-home order and adoption of a mask use resolution, COVID-19 incidence in the Blackfeet Tribal Reservation decreased by a factor of 33 from its peak of 6.40 cases per 1,000 residents per day on October 5 to 0.19 on November 7. Other mitigation measures the Blackfeet Tribal Reservation used included closing the east gate of Glacier National Park for the summer tourism season, instituting remote learning for public school students throughout the fall semester, and providing a Thanksgiving meal to every household to reduce trips to grocery stores. CDC has recommended use of routine public health interventions for infectious diseases, including case investigation with prompt isolation, contact tracing, and immediate quarantine after exposure to prevent and control transmission of SARS-CoV-2, the virus that causes COVID-19 (3). Stay-at-home orders, physical distancing, and mask wearing indoors, outdoors when physical distancing is not possible, or when in close contact with infected or exposed persons are also recommended as nonpharmaceutical community mitigation measures (3,4). Implementation and strict enforcement of stay-at-home orders and a mask use mandate likely helped reduce the spread of COVID-19 in the Blackfeet Tribal Reservation.
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http://dx.doi.org/10.15585/mmwr.mm7014a3DOI Listing
April 2021

Experiences of peer support specialists supervised by nonpeer supervisors.

Psychiatr Rehabil J 2021 Apr 1. Epub 2021 Apr 1.

Department of Psychiatric Rehabilitation and Counseling Professions, School of Health Professions, Rutgers the State University.

Objective: This article reports on a qualitative study examining the experiences of peer support specialists (PSS) supervised by nonpeer supervisors (NPS) in adult community mental health settings.

Method: Potential participants completed a demographic survey designed to address inclusionary criteria. From those eligible, a random number generator selected participants to be interviewed using a semistructured interview guide. The critical incident technique was used to elicit memorable experiences of supervision. Data were analyzed thematically. Twenty interviews were completed before saturation was reached.

Results: Thematic analysis revealed eight major themes including supervisor attitudes, role integration, trauma-informed supervisory techniques, facilitative/supportive environment, perspective-taking, mutual learning, opportunities for peer networking, and the desire for a supervisor who was a more experienced peer support worker.

Conclusions And Implications For Practice: PSS are integrating into a mental health service system transitioning from a medical model to a recovery-oriented model of care. NPS are the necessary guides who assist the PSS in navigating a system not yet aligned with peer values. If the mental health system is going to successfully become recovery oriented, NPS need a unique skill set to support those with lived experience whose recovery can help point the way. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/prj0000475DOI Listing
April 2021

Ebola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease.

N Engl J Med 2021 04;384(13):1240-1247

From the Institut National de Recherche Biomédicale (P.M.-K., A.N.-N., E.K.-L., A.A., D.M., N.B., D.K., B.N., M.A., O.T., S.M, S.A.-M., J.-J.M.T.), the University of Kinshasa (P.M.-K., A.N.-N., F.M., F.E., M.M., J.B.B., S.A.-M., J.-J.M.T.), and Ministère de la Santé (F.B., V.E., E.S.-P., Y.T.T.N.) - all in Kinshasa, Democratic Republic of Congo; the University of Nebraska Medical Center, Omaha (C.P., B.W., M.R.W.); International Medical Corps (M.M.-R.) and the University of California, Los Angeles (A.W.R., M.A.S.), Los Angeles, and the Scripps Research Institute, La Jolla (M.G.P., K.G., E.S., A.T., K.G.A.) - all in California; the Fred Hutchinson Cancer Research Center, Seattle (A.B., J.H., T.B.); the Institut Pasteur de Dakar, Dakar, Senegal (M.F., M.M.D., O.F., A.S.); the Vaccine Research Center, National Institutes of Health, Bethesda (J.M., A.P., N.J.S.), and the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research (I.C.), and the Integrated Research Facility at Fort Detrick, National Institutes of Health (L.H.), Frederick - all in Maryland; the World Health Organization, Geneva (B.D., M.K., M.R.D.B., I.S.F., A.Y.); and the University of Edinburgh, Edinburgh, United Kingdom (A.R.).

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).
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http://dx.doi.org/10.1056/NEJMoa2024670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888312PMC
April 2021

The rise of artificial soil carbon inputs: Reviewing microplastic pollution effects in the soil environment.

Sci Total Environ 2021 Mar 19;780:146569. Epub 2021 Mar 19.

School of Environment and Science/Australian Rivers Institute, Griffith University, Nathan Campus, QLD 4111, Australia. Electronic address:

The surge in the use of plastic materials, its poor handling and disposal have led to an increase in microplastic pollution in terrestrial environments. Microplastic pollution in soils is of concern due to potential influences on soil properties which play a critical role in plant growth and soil fertility. Moreover, the soil environment is a key nexus linking the atmosphere, hydrosphere, biosphere and lithosphere, and thus represents a crucial conduit for pollutant migration from the anthroposphere. In this review we evaluate the effects of microplastics in the soil environment with a specific focus on physical properties and biological function in the rhizosphere. Our review reveals that agricultural sources, particularly plastic mulches and waste applications, represent the main source of soil microplastic inputs. Once in the soil environment, microplastic effects on soil properties are highly variable depending mainly on soil type and microplastic characteristics. Soil properties relating to erosion-risk (i.e., bulk density), structural integrity (i.e., aggregate stability, particularly micro-aggregate stability), and water-storage capacity (i.e., evaporation rate, desiccation) are generally adversely impacted by soil microplastic inputs. Soil microplastic effects on rhizosphere function (i.e., plant health and microbial activity) are remarkably varied with some studies revealing positive impacts, such as enhanced plant-symbiotic fungi associations, from soil plastic additions. However, all identified publications reported at least one detrimental MP-induced impact on plant responses. Finally, our review revealed associations between microplastic properties and soil functional parameters - in particular, polymer size and morphology control soil water-holding properties whereas polymer type influences plant response. These associations will be helpful in targeting future research directions on this important topic that intersects all of the Earth's spheres.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146569DOI Listing
March 2021

Childhood obesity prevention across borders: A National Institutes of Health commentary.

Obes Rev 2021 Mar 19:e13243. Epub 2021 Mar 19.

Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA.

In response to the increasing rates of childhood obesity, the United States and countries across Latin America have invested in research that tests innovative strategies and interventions. Despite this, progress has been slow, uneven, and sporadic, calling for increased knowledge exchange and research collaboration that accelerate the adaptation and implementation of promising childhood obesity interventions. To share research results, challenges, and proven intervention strategies among Latin American and US researchers, particularly those working with Latino and Latin American populations, the National Institutes of Health (NIH) convened researchers from the United States and Latin America to highlight synergies between research conducted in Latin America and among Latino populations in the United States with the goal of catalyzing new relationships and identifying common research questions and strategies. This article highlights the NIH's research and priorities in childhood obesity prevention as well as areas for future direction, including overarching NIH plans and NIH institutes, centers, and offices investments in specific areas related to childhood obesity prevention in Latin America and/or among Latino populations in the United States.
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http://dx.doi.org/10.1111/obr.13243DOI Listing
March 2021

The Mafb cleft-associated variant H131Q is not required for palatogenesis in the mouse.

Dev Dyn 2021 Mar 14. Epub 2021 Mar 14.

Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, Iowa, USA.

Background: Orofacial clefts (OFCs) are common birth defects with complex etiology. Genome wide association studies for OFC have identified SNPs in and near MAFB. MAFB is a transcription factor critical for structural development of digits, kidneys, skin, and brain. MAFB is also expressed in the craniofacial region. Previous sequencing of MAFB in a Filipino population revealed a novel missense variant significantly associated with an increased risk for OFC. This MAFB variant, leading to the amino acid change H131Q, was knocked into the mouse Mafb, resulting in the Mafb allele. The Mafb construct was engineered to allow for deletion of Mafb ("Mafb ").

Results: Mafb animals died shortly after birth. Conversely, Mafb mice survived into adulthood at Mendelian ratios. Mafb and Mafb heads exhibited normal macroscopic and histological appearance at all embryonic time points evaluated. The periderm was intact based on expression of keratin 6, p63, and E-cadherin. Despite no effect on craniofacial morphogenesis, H131Q inhibited the Mafb-dependent promoter activation of Arhgap29 in palatal mesenchymal, but not ectodermal-derived epithelial cells in a luciferase assay.

Conclusions: Mafb is dispensable for murine palatogenesis in vivo, and the cleft-associated variant H131Q, despite its lack of morphogenic effect, altered the expression of Arhgap29 in a cell-dependent context.
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http://dx.doi.org/10.1002/dvdy.327DOI Listing
March 2021

Understanding Users' Perspectives of Psychosocial Mechanisms Underpinning Peer Support Work in Chile.

Community Ment Health J 2021 Mar 1. Epub 2021 Mar 1.

New York State Psychiatric Institute, New York, NY, USA.

This study explores the beliefs and attitudes about the psychosocial mechanisms of peer support work among users who participated in Critical Time Intervention-Task Shifting (CTI-TS), which tested the acceptability and feasibility of a peer support work model to improve community-based mental health care for individuals with psychosis in Latin America. We conducted a secondary analysis of 15 in-depth interviews with CTI-TS participants in Chile, using the framework method and defined the framework domains based on five major mechanisms of peer support work identified by a recent literature review. The analysis revealed that users' perceptions of peer support work mechanisms were strongly shaped by personal motivations, beliefs about professional hierarchies, familial support, and the Chilean mental health system's incipient recovery orientation. The findings underscore the importance of adopting culturally tailored strategies to promote peer support work, such as involving mental health professionals and fostering equal-powered relationships between PSWs and users.
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http://dx.doi.org/10.1007/s10597-021-00800-1DOI Listing
March 2021

News from NHLBI: Nutrition Research at the National Heart, Lung, and Blood Institute and Future Opportunities.

J Nutr 2021 Mar;151(3):598-604

Clinical Applications and Preventions Branch, Division of Cardiovascular Science, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.

Background: Nutrition plays a major role in the prevention and treatment of cardiovascular and other chronic diseases; hence, nutrition research is a priority for the National Heart, Lung, and Blood Institute (NHLBI). The purpose of this analysis is to describe the scope of NHLBI-funded extramural nutrition research grants over the past decade and offer insights into future opportunities for nutrition research relevant to NHLBI's mission.

Methods: Data were extracted using the Research, Condition, and Disease Categorization spending categories from the publicly available NIH Research Portfolio Online Reporting Tool Expenditures and Results. New 2018 and 2019 grants were coded into categories and mapped to the 2016 NHLBI Strategic Vision priorities.

Results: Approximately 90% of nutrition research funds supported extramural grants, particularly through investigator-initiated R series grants (69.6%). Of these, 19.8% were classified as clinical trials. Consistent nutrition-related topics, including physical activity, weight loss, fatty acids, metabolic syndrome, childhood obesity, and other topics such as gut microbiota, arterial stiffness, sleep duration, and meal timing, emerged in 2014-2019.  Mapping of the NHLBI Strategic Vision objectives revealed that 32% of newly funded grants focused on pathobiological mechanisms important to the onset and progression of heart, lung, blood, and sleep disorders, with opportunities including developing novel diagnostic and therapeutic strategies and clinical and implementation science research.

Discussion: The findings show the breadth of NHLBI-funded nutrition research and highlight potential research opportunities for nutrition scientists.
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http://dx.doi.org/10.1093/jn/nxaa413DOI Listing
March 2021

"Super-Spreaders" and Person-to-Person Transmission of Andes Virus in Argentina.

N Engl J Med 2020 12;383(23):2230-2241

From Laboratorio Nacional de Referencia de Hantavirus (V.P.M., D.O.A., C.M.B., A.A.I., R.M.C., N.P.) and Plataforma Genomica (B.L., D.C., J.C.), Instituto Nacional de Enfermedades Infecciosas, and Unidad Operativa Centro de Contención Biológica (A.E.), Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán (C.P.), Secretaría de Gobierno de Salud (M.I.B., M.K., A.R.), Área Programática Esquel (J.D., E.B.), and Hospital Zonal de Esquel (L.L., C.A., C.P.O., E.L.), Ministerio de Salud de Chubut, Esquel, and Argentina Ministerio de Salud de Chubut, Rawson (T.S.), Chubut, and Hospital Zonal de Bariloche Dr. Ramón Carrillo, Ministerio de Salud de Río Negro, San Carlos de Bariloche, Río Negro (F.P.) - all in Argentina; the Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases (N.D.P., U.P.-S., P.A.L., E.R.N., J.A.C., C.B.P., J.R.K., M.S.-L., G.P.), and the Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health (H.S., B.D.-K., J.H.K.), Fort Detrick, Frederick, MD; and the College of Public Health (C.B.P.) and Department of Pathology and Microbiology (M.S.-L.), University of Nebraska Medical Center, Omaha.

Background: From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions.

Methods: Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events.

Results: After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission.

Conclusions: Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission. (Funded by the Ministerio de Salud y Desarrollo Social de la Nación Argentina and others.).
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http://dx.doi.org/10.1056/NEJMoa2009040DOI Listing
December 2020

Novel Rickettsia Species Infecting Dogs, United States.

Emerg Infect Dis 2020 12;26(12):3011-3015

In 2018 and 2019, spotted fever was suspected in 3 dogs in 3 US states. The dogs had fever and hematological abnormalities; blood samples were Rickettsia seroreactive. Identical Rickettsia DNA sequences were amplified from the samples. Multilocus phylogenetic analysis showed the dogs were infected with a novel Rickettsia species related to human Rickettsia pathogens.
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http://dx.doi.org/10.3201/eid2612.200272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706976PMC
December 2020

Which behavioral health screening tool should you use-and when?

J Fam Pract 2020 Nov;69(9):454-460

Robert J. Dole VA Medical Center, Wichita, KS, USA.

This review focuses on screens to assess everything from mood and substance use to pain and cognition. It also offers an algorithm to aid with clinical decision making.
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November 2020

Ultrasonic mapping of hybrid additively manufactured 420 stainless steel.

Ultrasonics 2021 Feb 7;110:106269. Epub 2020 Oct 7.

Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA. Electronic address:

Metal hybrid additive manufacturing (AM) processes are suitable to create complex structures that advance engineering performance. Hybrid AM can be used to create functionally graded materials for which the variation in microstructure and material properties across the domain is created through a synergized combination of fully-coupled manufacturing processes and/or energy sources. This expansion in the engineering design and manufacturing spaces presents challenges for nondestructive evaluation, including the assessment of the sensitivity of nondestructive measurements to functional gradients. To address this problem, linear ultrasound measurements are used to interrogate 420 stainless steel coupons from three manufacturing methods: wrought, AM, and hybrid AM (directed energy deposition + laser peening). Wave speed, attenuation, and diffuse backscatter results are compared with microhardness measurements along the build/axial direction of the coupons, while microstructure images are used for qualitative verification. The ultrasound measurements compare well with the destructive measurements without any substantial loss in resolution. Furthermore, ultrasonic methods are shown to be effective for identification of the gradient and cyclic nature of the elastic properties and microstructure on the hybrid AM coupon. These results highlight the potential of ultrasound as an efficient and accessible nondestructive characterization method for hybrid AM samples and inform further nondestructive evaluation decisions in AM.
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http://dx.doi.org/10.1016/j.ultras.2020.106269DOI Listing
February 2021

Dietary patterns and associations with BMI in low-income, ethnic minority youth in the USA according to baseline data from four randomised controlled trials.

Br J Nutr 2020 Sep 30:1-11. Epub 2020 Sep 30.

Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC27599, USA.

Few studies have derived data-driven dietary patterns in youth in the USA. This study examined data-driven dietary patterns and their associations with BMI measures in predominantly low-income, racial/ethnic minority US youth. Data were from baseline assessments of the four Childhood Obesity Prevention and Treatment Research (COPTR) Consortium trials: NET-Works (534 2-4-year-olds), GROW (610 3-5-year-olds), GOALS (241 7-11-year-olds) and IMPACT (360 10-13-year-olds). Weight and height were measured. Children/adult proxies completed three 24-h dietary recalls. Dietary patterns were derived for each site from twenty-four food/beverage groups using k-means cluster analysis. Multivariable linear regression models examined associations of dietary patterns with BMI and percentage of the 95th BMI percentile. Healthy (produce and whole grains) and Unhealthy (fried food, savoury snacks and desserts) patterns were found in NET-Works and GROW. GROW additionally had a dairy- and sugar-sweetened beverage-based pattern. GOALS had a similar Healthy pattern and a pattern resembling a traditional Mexican diet. Associations between dietary patterns and BMI were only observed in IMPACT. In IMPACT, youth in the Sandwich (cold cuts, refined grains, cheese and miscellaneous) compared with Mixed (whole grains and desserts) cluster had significantly higher BMI (β = 0·99 (95 % CI 0·01, 1·97)) and percentage of the 95th BMI percentile (β = 4·17 (95 % CI 0·11, 8·24)). Healthy and Unhealthy patterns were the most common dietary patterns in COPTR youth, but diets may differ according to age, race/ethnicity or geographic location. Public health messages focused on healthy dietary substitutions may help youth mimic a dietary pattern associated with lower BMI.
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http://dx.doi.org/10.1017/S0007114520003852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007675PMC
September 2020

Applying the Behavior Change Technique Taxonomy to Four Multicomponent Childhood Obesity Interventions.

West J Nurs Res 2021 May 10;43(5):468-477. Epub 2020 Sep 10.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Applying the Behavior Change Technique Taxonomy has the potential to facilitate identification of effective childhood obesity intervention components. This article evaluates the feasibility of coding Childhood Obesity Prevention and Treatment Consortium interventions and compares reliability between external taxonomy-familiar coders and internal intervention-familiar coders. After training, coder pairs independently coded prespecified portions of intervention materials. An adjudication process was used to explore coding discrepancies. Reliability between internal and external coders was moderate (prevalence and bias-adjusted kappa .38 to .55). Reliability for specific target behaviors varied with substantial agreement for physical activity (.63 to .76) and moderate for dietary intake (.44 to .63). Applying the taxonomy to these interventions was feasible, but agreement was modest. Coding discrepancies highlight the importance of refining coding to capture the complexities of childhood obesity interventions, which often engage multiple recipients (e.g., parents and/or children) and address multiple behaviors (e.g., diet, physical activity, screen time).
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http://dx.doi.org/10.1177/0193945920954782DOI Listing
May 2021

Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.

PLoS One 2020 20;15(7):e0235295. Epub 2020 Jul 20.

The Jackson Laboratory, Bar Harbor, ME, United States of America.

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235295PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371178PMC
September 2020

Healthier Food and Beverage Interventions in Schools: Four Community Guide Systematic Reviews.

Am J Prev Med 2020 07;59(1):e15-e26

Perelman School of Medicine and School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania.

Context: Healthy eating during childhood is important for optimal growth and helps reduce the risk of obesity, which has potentially serious health consequences. Changing the school food environment may offer one way to improve students' dietary intake. This manuscript reports 4 Community Guide systematic reviews examining the effectiveness of interventions in schools promoting healthy eating and weight.

Evidence Acquisition: School obesity prevention programs aiming to improve diet were identified from a 2013 Agency for Health Care Research and Quality systematic review and an updated search (August 2012-January 4, 2017). In 2017-2018, Community Guide systematic review methods were used to assess effectiveness as determined by dietary behavior and weight changes.

Evidence Synthesis: Interventions improving school meals or offering fruits and vegetables (n=27 studies) are considered effective. Evidence is insufficient to determine the effectiveness of interventions supporting healthier snack foods and beverages outside of school meal programs given inconsistent findings (n=13 studies). Multicomponent interventions to increase availability of healthier foods and beverages are considered effective. These interventions must include 1 component from school meals or fruit and vegetable programs and interventions supporting healthier snack foods and beverages (n=12 studies). There is insufficient evidence to determine the effectiveness of interventions to increase water access because only 2 studies met inclusion criteria.

Conclusions: A total of 2 school-based dietary interventions have favorable effects for improving dietary habits and modest effects for improving or maintaining weight. More evidence is needed regarding interventions with insufficient findings. These reviews may inform researchers and school administrators about healthy eating and obesity prevention interventions.
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http://dx.doi.org/10.1016/j.amepre.2020.01.011DOI Listing
July 2020

Rapid 3D Enhanced Resolution Microscopy Reveals Diversity in Dendritic Spinule Dynamics, Regulation, and Function.

Neuron 2020 08 27;107(3):522-537.e6. Epub 2020 May 27.

Department of Physiology, Northwestern University, Chicago, IL 60611, USA; Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL 60611, USA. Electronic address:

Dendritic spinules are thin protrusions, formed by neuronal spines, not adequately resolved by diffraction-limited light microscopy, which has limited our understanding of their behavior. Here we performed rapid structured illumination microscopy and enhanced resolution confocal microscopy to study spatiotemporal spinule dynamics in cortical pyramidal neurons. Spinules recurred at the same locations on mushroom spine heads. Most were short-lived, dynamic, exploratory, and originated near simple PSDs, whereas a subset was long-lived, elongated, and associated with complex PSDs. These subtypes were differentially regulated by Ca transients. Furthermore, the postsynaptic Rac1-GEF kalirin-7 regulated spinule formation, elongation, and recurrence. Long-lived spinules often contained PSD fragments, contacted distal presynaptic terminals, and formed secondary synapses. NMDAR activation increased spinule number, length, and contact with distal presynaptic elements. Spinule subsets, dynamics, and recurrence were validated in cortical neurons of acute brain slices. Thus, we identified unique properties, regulatory mechanisms, and functions of spinule subtypes, supporting roles in neuronal connectivity.
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http://dx.doi.org/10.1016/j.neuron.2020.04.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879711PMC
August 2020

Designing for effective controlled release in agricultural products: new insights into the complex nature of the polymer-active agent relationship and implications for use.

J Sci Food Agric 2020 Oct 22;100(13):4723-4733. Epub 2020 Jun 22.

School of Chemical Engineering, University of Queensland, QLD, Brisbane, Australia.

Background: Various active chemical agents, such as soil microbial inhibitors, are commonly applied to agricultural landscapes to optimize plant yields or minimize unwanted chemical transformations. Dicyandiamide (DCD) is a common nitrification inhibitor. However, it rapidly decomposes under warm and wet conditions, losing effectiveness in the process. Blending DCD with an encapsulating polymer matrix could help overcome this challenge and slow its release. Here, we encapsulated DCD in a biodegradable matrix of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and investigated the effects of DCD crystal size and loading rates on release rates.

Results: Three DCD crystal size fractions (0-106, 106-250 and 250-420 μm) were blended with PHBV at 200, 400, 600 and 800 gkg loadings through extrusion processing and release kinetics were studied in water over 8 weeks. For loadings ≥ 600 g kg , more than 95% release was reached within the first 7 days. By contrast, at 200 g kg loading only 10%, 36% and 57% of the DCD was mobilized after 8 weeks in water for 0 to 106 μm, 106 to 250 μm and 250 to 420 μm crystal size fractions, respectively.

Conclusion: The lower percolation threshold for this combination of materials lies between 200 and 400 g kg DCD loading. The grind size fraction of DCD significantly affects the quantity of burst release from the surface of the pellet, particularly below the lower percolation threshold. The results presented here are likely translatable to the encapsulation and release of other crystalline materials from hydrophobic polymer matrices used in controlled release formulations, such as fertilizers, herbicides and pesticides. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10531DOI Listing
October 2020

Nutrition Disparities and Cardiovascular Health.

Curr Atheroscler Rep 2020 05 21;22(4):15. Epub 2020 May 21.

Division of Cardiovascular Sciences, NHLBI, NIH, 6710 Rockledge Drive, Suite 10115, Bethesda, MD, 20892, USA.

Purpose Of Review: This review is an assessment of the state of the science on nutrition disparities and their contribution to disparities in cardiovascular health.

Recent Findings: Nutrition disparities remain pervasive by race/ethnicity, sex/gender, socioeconomic status, and geography. They are rooted in differences in social, cultural, and environmental determinants of health, behavioral and lifestyle factors, and the impact of policy interventions. Systematic differences in diet quality, dietary patterns, and nutrient intakes contribute to cardiovascular disparities and are mediated by microbiota, and CVD risk factors including high levels of blood pressure, low density lipoprotein cholesterol (LDL), and glucose; oxidative stress, pro-inflammatory cytokines, and endothelial dysfunction. Despite the progress made in nutrition research, important gaps persist that signal the need for more effective interventions at multiple levels to reduce cardiovascular disparities. Research opportunities include (1) exploring the gene-nutrient-environment interactions in the context of ancestral diversity; (2) investigating the causal link between diet and gut microbiota and impact of social determinants of health; (3) understanding resilience; (4) testing the effectiveness of multi-level interventions that address social and environmental determinants; and (4) supporting intervention research informed by validated implementation science frameworks.
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http://dx.doi.org/10.1007/s11883-020-0833-3DOI Listing
May 2020

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials.

J Cardiovasc Pharmacol Ther 2020 09 18;25(5):409-417. Epub 2020 May 18.

Department of Cardiology, Saint Francis Hospital and Medical Center, Hartford, CT, USA.

Background: Previous meta-analyses have shown that statins may cause incident diabetes. This article reviews randomized controlled trials using proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) or ezetimibe on the risk of new-onset diabetes.

Methods: Eight trials involving PCSK9i and 3 trials of ezetimibe were selected for review. PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were thoroughly searched for relevant trials. Inclusion criteria included at least 100 patients per treatment arm, follow-up of at least 52 weeks, and at least double-blinded study design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized, placebo-controlled, open-label, and crossover trials. The primary outcome was the number of incident diabetes cases. A random effects model was used. Heterogeneity in effect sizes was measured with parameter and the statistic was used to test for excessive between-study heterogeneity.

Results: A total of 52 214 participants for the PCSK9i and a total of 20 084 for the ezetimibe meta-analyses were included. Participants randomized to PCSK9i did not differ from the control patients in diabetes incidence (risk ratio [RR] = 0.99, = .87, 95% CI = 0.92-1.07). Participants randomized to ezetimibe did not differ from the control patients in diabetes incidence (RR = 1.05, = .37, 95% CI = 0.95-1.15).

Discussion: The use of PCSK9i and ezetimibe does not appear to impact the risk of incident diabetes mellitus when added to guideline-directed medical therapy.
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http://dx.doi.org/10.1177/1074248420924983DOI Listing
September 2020

Baseline diet quality of predominantly minority children and adolescents from households characterized by low socioeconomic status in the Childhood Obesity Prevention and Treatment Research (COPTR) Consortium.

BMC Nutr 2019 9;5:38. Epub 2019 Sep 9.

6Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health, Bethesda, MD USA.

Background: The Healthy Eating Index (HEI-2010) is a measure of diet quality that examines conformance with the Dietary Guidelines for Americans. The objectives of this study were to estimate baseline diet quality of predominantly low-income minority children using the HEI-2010 and to identify the most important HEI components to target for dietary intervention.

Methods: Two or three baseline 24 h dietary recalls were collected in-person or over telephone between May 2012 and June 2014 from 1,745 children and adolescents from four randomized clinical trials in the Childhood Obesity Prevention and Treatment Research (COPTR) Consortium. Nine adequacy and three moderation food components were calculated and averaged to determine overall HEI scores. The overall HEI-2010 scores were categorized as ≥81, 51-80, or ≤ 50 based on the HEI-2005 classification. For each study, mean overall and component HEI scores were estimated using linear regression models.

Results: Mean (95% CI) overall HEI scores ranged from 47.9 (46.8, 49.0) to 64.5 (63.6, 65.4). Only 0.3 to 8.1% of children and adolescents had HEI-2010 score ≥ 81. The average component score for green and beans was less than 30% of maximum score for all trials. In contrast, the average component score for protein, dairy (except for IMPACT), and empty calories (except forIMPACT) was more than 80% of maximum score.

Conclusions: Based on HEI-2010 scores, few children and adolescents consumed high quality diets. Dietary interventions for children and adolescents should focus on improving intakes of green vegetables and beans.

Clinical Trial Registry Numbers: GROW study (clinical trial # NCT01316653); NET-Works study (clinical trial #NCT01606891); Stanford Goals (clinical trial #NCT01642836); IMPACT (clinical trial # NCT01514279).
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http://dx.doi.org/10.1186/s40795-019-0302-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050800PMC
September 2019

Radical α-C-H Cyclobutylation of Aniline Derivatives.

Synlett 2020 Jan 3;31(1):51-54. Epub 2019 Sep 3.

Department of Chemistry, Emory University, Atlanta, GA 30322, USA.

A catalytic system has been developed for the direct alkylation of α-C-H bonds of aniline derivatives with strained C-C σ-bonds. This method operates through a photoredox mechanism in which oxidative formation of aminoalkyl radical intermediates enables addition to a bicyclobutane derivative, giving rise to α-cyclobutyl -alkylaniline products. This mild system proceeds through a redox- and proton-neutral mechanism and is operational for a range of substituted arylamine derivatives.
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http://dx.doi.org/10.1055/s-0039-1690197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043791PMC
January 2020

A prospective randomized, double-blinded clinical study evaluating the efficacy and safety of bupivacaine versus morphine-bupivacaine in caudal epidurals in cats with urethral obstruction.

J Vet Emerg Crit Care (San Antonio) 2020 Mar 26;30(2):170-178. Epub 2020 Feb 26.

Department of Clinical Sciences and Advanced Medicine-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To investigate the efficacy and safety of the caudal epidural technique in cats with urethral obstruction (UO).

Design: Prospective, double-blinded, randomized, sham-controlled study.

Animals: Eighty-eight male cats with UO.

Interventions: Thirty cats randomized to bupivacaine epidural (BUP), 28 cats to bupivacaine-morphine epidural (BUP/MOR), and 30 cats to sham epidural (SHAM).

Measurements And Main Results: Time to perform the epidural and efficacy of the epidural was assessed by evaluation of tail and perineal responses. The amount of propofol for urinary catheterization and time to administration of rescue analgesia (buprenorphine) was recorded. Cats were monitored for epidural complications. The median time to perform the epidural was 2 min (range, 0.2-13 min and range, 0.5-13 min), with an epidural success rate of 70%. The median amount of propofol administered for urinary catheterization was significantly less in the BUP (2.1 mg/kg; range, 0-7.5 mg/kg) and MOR/BUP cats (1.85 mg/kg; range, 0-8.6 mg/kg) as compared to SHAM cats (4 mg/kg; range, 0-12.7 mg/kg) (P = 0.006, P = 0.0008, respectively). The median time to administration of rescue analgesia was also significantly longer in the BUP (10 h; range, 2-32 h) and MOR/BUP cats (10 h; range, 4-45 h) as compared to SHAM cats (4 h; range, 2-36 h) (P = 0.0026, P = 0.0004, respectively). There were no recognized complications related to the epidural.

Conclusion: Caudal epidural appears to be safe, may reduce the amount of IV anesthesia needed to facilitate urinary catheterization, and can be used to provide long-term analgesia in the hospital.
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http://dx.doi.org/10.1111/vec.12944DOI Listing
March 2020

Molecular sequencing and morphological identification reveal similar patterns in native bee communities across public and private grasslands of eastern North Dakota.

PLoS One 2020 23;15(1):e0227918. Epub 2020 Jan 23.

U.S. Geological Survey, Northern Prairie Wildlife Research Center, Jamestown, North Dakota, United States of America.

Bees play a key role in the functioning of human-modified and natural ecosystems by pollinating agricultural crops and wild plant communities. Global pollinator conservation efforts need large-scale and long-term monitoring to detect changes in species' demographic patterns and shifts in bee community structure. The objective of this project was to test a molecular sequencing pipeline that would utilize a commonly used locus, produce accurate and precise identifications consistent with morphological identifications, and generate data that are both qualitative and quantitative. We applied this amplicon sequencing pipeline to native bee communities sampled across Conservation Reserve Program (CRP) lands and native grasslands in eastern North Dakota. We found the 28S LSU locus to be more capable of discriminating between species than the 18S SSU rRNA locus, and in some cases even resolved instances of cryptic species or morphologically ambiguous species complexes. Overall, we found the amplicon sequencing method to be a qualitatively accurate representation of the sampled bee community richness and species identity, especially when a well-curated database of known 28S LSU sequences is available. Both morphological identification and molecular sequencing revealed similar patterns in native bee community structure across CRP lands and native prairie. Additionally, a genetic algorithm approach to compute taxon-specific correction factors using a small subset of the most concordant samples demonstrated that a high level of quantitative accuracy could be possible if the specimens are fresh and processed soon after collection. Here we provide a first step to a molecular pipeline for identifying insect pollinator communities. This tool should prove useful for future national monitoring efforts as use of molecular tools becomes more affordable and as numbers of 28S LSU sequences for pollinator species increase in publicly-available databases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227918PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977755PMC
April 2020

Birth outcomes with prescribed chronic and acute opioid exposure during pregnancy.

J Opioid Manag 2019 Sep/Oct;15(5):407-415

Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado.

Objectives: To assess the effects of no, any, and acute and chronic prescription opioid exposure for pain during pregnancy on maternal and fetal outcomes.

Design: Retrospective cohort study.

Setting: Integrated healthcare delivery system. Information on pregnancies and their outcomes were obtained from administrative data and verified via manual chart review.

Participants: Women ≥ 18 years of age who were pregnant between January 1, 2012 and May 31, 2015 and had chronic, acute, and no opioid exposure; defined as an ambulatory dispensing(s) of >30 (with a total of 225 morphine equivalents), 1-29, and 0 days supply of opioid, respectively, during pregnancy.

Main Outcome Measure: Non-live birth.

Results: A total 13,809 pregnancies for 13,131 women were included. Pregnancies with opioid exposure had higher risk scores and more comorbid conditions. A total of 1,319 (9.6 percent) pregnancies had any documented opioid exposure during pregnancy with 125 (1.0 percent) and 1,194 (8.7 percent) pregnancies having had chronic and acute opioid exposure, respectively. Pregnancies with acute opioid exposure had a higher percentage of non-live births (3.1 percent) compared to pregnancies (1.0 percent) with no opioid exposure (adjusted odds ratio = 3.46, 95% confidence interval 2.33-5.14) but no difference compared to pregnancies with chronic (1.6 percent) opioid exposure (p > 0.05 with adjustment).

Conclusions: While a dose response of opioid exposure was not identified, these results add to existing evidence that opioid exposure during pregnancy is correlated with negative outcomes. Practitioners may better serve pregnant women and their fetuses by encouraging alternate pain relief treatments.
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http://dx.doi.org/10.5055/jom.2019.0529DOI Listing
January 2020

The Effect of Bifidobacterium on Reducing Symptomatic Abdominal Pain in Patients with Irritable Bowel Syndrome: A Systematic Review.

Probiotics Antimicrob Proteins 2020 09;12(3):834-839

School of Food Science and Nutrition, University of Leeds, Leeds, UK.

Probiotics, specifically Bifidobacteria, may improve abdominal pain in patients with irritable bowel syndrome (IBS); however, results from randomised controlled trials (RCTs) are conflicting. Here, we systematically reviewed the efficacy of Bifidobacteria on abdominal pain in IBS. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to 20 May 2019, without language or date restrictions. The search strategy comprised of the combination of three concepts: supplementation, abdominal pain, and IBS. Inclusion criteria included double-blind placebo-controlled RCTs featuring Bifidobacteria supplementation in Rome-diagnosed IBS patients. A total of 8 RCTs involving a total of 1045 patients with Rome diagnosed IBS were included. The dose of total Bifidobacteria ranged from 10 to > 10 cfu (colony-forming unit) and duration of supplementation ranged between 2 and 8 weeks. Bifidobacteria was delivered through either intake of fermented milk products, encapsulation or via a malted milk beverage, with all studies assessing abdominal pain via a visual analogue Likert scale. From the studies included, 50% (n = 4) of studies found a statistically significant improvement in abdominal pain following Bifidobacteria supplementation compared to placebo, 38% (n = 3) of studies found non-significant improvements and 12% (n = 1) showed a statistically significant dose-response effect of improvement. The evidence shows a heterogeneity of effect for Bifidobacteria dependent upon strain, dosage and delivery method. While not all studies demonstrate significant improvements in abdominal pain, none of the selected studies reported an increase in pain or other adverse effects.
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http://dx.doi.org/10.1007/s12602-019-09609-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456408PMC
September 2020

CNTNAP2 is targeted to endosomes by the polarity protein PAR3.

Eur J Neurosci 2020 02 2;51(4):1074-1086. Epub 2019 Dec 2.

Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

A decade of genetic studies has established contactin-associated protein-like 2 (CNTNAP2) as a prominent susceptibility gene associated with multiple neurodevelopmental disorders. The development and characterization of Cntnap2 knockout models in multiple species have bolstered this claim by establishing clear connections with certain endophenotypes. Despite these remarkable in vivo findings, CNTNAP2's molecular functions are relatively unexplored, highlighting the need to identify novel protein partners. Here, we characterized an interaction between CNTNAP2 and partitioning-defective 3 (PAR3)-a polarity molecule isolated in a yeast two-hybrid screen with CNTNAP2's C-terminus. We provide evidence that the two proteins interact via PDZ domain-mediated binding, that CNTNAP2 /PAR3 complexes are largely associated with clathrin-coated endocytic vesicles in heterologous cells and that PAR3 causes an enlargement of CNTNAP2 puncta size. Live imaging and fluorescence recovery after photobleaching (FRAP) reveals that PAR3 limits the mobility of CNTNAP2. Finally, overexpression of PAR3 but not a PAR3 mutant lacking all PDZ domains (PAR3∆PDZall) can cluster endogenous CNTNAP2 in primary neurons. Collectively, we conclude that PAR3 regulates CNTNAP2 spatial localization.
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http://dx.doi.org/10.1111/ejn.14620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069803PMC
February 2020

Advancing Nutrition Education, Training, and Research for Medical Students, Residents, Fellows, Attending Physicians, and Other Clinicians: Building Competencies and Interdisciplinary Coordination.

Adv Nutr 2019 11;10(6):1181-1200

Office of Nutrition Research, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.

Nutrition plays an important role in health promotion and disease prevention and treatment across the lifespan. Physicians and other healthcare professionals are expected to counsel patients about nutrition, but recent surveys report minimal to no improvements in medical nutrition education in US medical schools. A workshop sponsored by the National Heart, Lung, and Blood Institute addressed this gap in knowledge by convening experts in clinical and academic health professional schools. Representatives from the National Board of Medical Examiners, the Accreditation Council for Graduate Medical Education, the Liaison Committee on Medical Education, and the American Society for Nutrition provided relevant presentations. Reported is an overview of lessons learned from nutrition education efforts in medical schools and health professional schools including interprofessional domains and competency-based nutrition education. Proposed is a framework for coordinating activities of various entities using a public-private partnership platform. Recommendations for nutrition research and accreditation are provided.
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http://dx.doi.org/10.1093/advances/nmz083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855992PMC
November 2019