54 results on '"Klein DK"'
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2. Children and Youth with Special Health Care Needs: Progress Towards More Family-Centered Systems of Care.
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Walker DK, Perrin JM, Wells N, Vessey JA, and DiFazio RL
- Abstract
Children and youth with special health care needs have increasingly been included in community and society over the past 50 years. Changing definitions and programs in the education, health, and public health/Title V sectors document this greater inclusion. The most profound change was in the education system, with the passage of legislative mandates for inclusion and parental rights. Although the health system has no similar universal mandate, the sequential passage of Medicaid, Children's Health Insurance Plan, and the Patient Protection and Affordable Care Act led to expanded health care coverage with no pre-existing conditions and lifetime caps. Title V of the Social Security Act, originally passed in 1935, evolved from a focus on individual medical services to a public health systems approach focusing on building family-centered, coordinated, comprehensive care in community settings. Most of the changes in all the sectors are the result of the advocacy and engagement of parents and families; the Maternal and Child Health Bureau was a supportive and innovative leader for family-professional partnerships. Much work on understanding disparities across the sectors has led to more recent focus on equity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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3. Sex differences in outcomes of patients undergoing on-pump coronary artery bypass grafting surgery.
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Ferreira DK, Petzold AP, Zawislak RB, Oliveira JR, Wagner MB, Piantá RM, Kalil RAK, Guaragna JCVDC, and Bodanese LC
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- Humans, Male, Female, Aged, Middle Aged, Retrospective Studies, Risk Factors, Sex Factors, Treatment Outcome, Coronary Artery Disease surgery, Coronary Artery Disease mortality, Sex Characteristics, Coronary Artery Bypass adverse effects, Coronary Artery Bypass mortality, Hospital Mortality, Postoperative Complications epidemiology, Postoperative Complications etiology, Postoperative Complications mortality
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There are controversies regarding the impact of sex on mortality and postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG), although some studies demonstrate comparable outcomes. This study sought to evaluate sex differences regarding risk factors associated with hospital mortality and postoperative clinical outcomes among patients undergoing isolated on-pump CABG. We conducted a retrospective observational cohort study of patients who underwent isolated on-pump CABG from January 1996 to January 2020. Patients were divided into two groups (male and female) and compared regarding preoperative characteristics, surgical technical variables, and in-hospital outcomes. All-cause mortality between groups was compared using logistic regression. Risk factors for mortality, along with their respective odds ratios (OR), were separately assessed using a logistic regression model with p-values for interaction. We analyzed 4,882 patients, of whom 31.6% were female. Women exhibited a higher prevalence of age >75 years (12.2% vs 8.3%, p<0.001), obesity (22.6% vs 11.5%, p<0.001), diabetes (41.6% vs 32.2%, p<0.001), hypertension (85.2% vs 73.5%, p<0.001), and NYHA functional classes 3 and 4 (16.2% vs 11.2%, p<0.001) compared to men. Use of the mammary artery for revascularization was less frequent among women (73.8% vs 79.9%, p<0.001), who also received fewer saphenous vein grafts (2.17 vs 2.27, p = 0.002). A history of previous or recent myocardial infarction (MI) had an impact on women's mortality, unlike in men (OR 1.61 vs 0.94, p = 0.014; OR 1.86 vs 0.99, p = 0.015, respectively). After adjusting for several risk factors, mortality was found to be comparable between men and women, with an OR of 1.20 (95% CI 0.94-1.53, p = 0.129). In conclusion, female patients undergoing isolated on-pump CABG presented with a higher number of comorbidities. Previous and recent MI were associated with higher mortality only in women. In this cohort analysis, female gender was not identified as an independent risk factor for outcome after CABG., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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4. Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation.
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Andreasson LM, Dyhre-Petersen N, Hvidtfeldt M, Jørgensen GØ, Von Bülow A, Klein DK, Uller L, Erjefält J, Porsbjerg C, and Sverrild A
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- Humans, Male, Cytokines, Eosinophils, Sputum, Asthma diagnosis, Asthma metabolism, Eosinophilia diagnosis, Eosinophilia metabolism, Inflammation diagnosis, Inflammation metabolism, Thymic Stromal Lymphopoietin metabolism
- Abstract
Background: Thymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR), and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes has been described sparsely., Objectives: This study sought to investigate the association between AHR and levels of TSLP in serum, sputum, and bronchoalveolar lavage in patients with asthma with and without type-2 inflammation., Methods: A novel ultrasensitive assay was used to measure levels of TSLP in patients with asthma (serum, n = 182; sputum, n = 81; bronchoalveolar lavage, n = 85) and healthy controls (serum, n = 47). The distribution and association among airway and systemic TSLP, measures of AHR, type-2 inflammation, and severity of disease were assessed., Results: TSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide (ρ = 0.49, P = .005). Serum TSLP was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: geometric mean: 1600 fg/mL (95% CI: 1468-1744 fg/mL) and 1294 fg/mL (95% CI: 1167-1435 fg/mL) versus 846 fg/mL (95% CI: 661-1082 fg/mL), but did not correlate with the level of AHR. Increasing age, male sex, and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, inhaled corticosteroid dose, and symptom score were not., Conclusions: The association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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5. Looking back, moving forward: An introduction to the special issue honoring the 100th anniversary of the global alliance for behavioral health and social justice.
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McLeigh JD, Jaffe G, Walker DK, Wertlieb D, Spaulding W, and Beardslee W
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- Humans, History, 20th Century, History, 21st Century, Mental Health, Mental Disorders therapy, Mental Disorders history, Societies, Medical history, Social Justice, Anniversaries and Special Events
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Since its founding, American Orthopsychiatric Association (AOA) has been at the forefront of working at the intersection of mental health and social justice. In Mental Health and Social Change: 50 Years of Orthopsychiatry (Shore & Mannino, 1975), former organization president and journal editor Milton Shore and Fortune Mannino wrote that the association had consistently held a philosophy that included (a) a commitment to an interdisciplinary approach in the study of mental health problems and the development of mental health programs; (b) an emphasis on prevention as well as treatment; (c) the integration of the clinical and the social; (d) a major focus on the social scene and its interweaving with mental health problems in individuals within society; and (e) an avoidance of dilettantism, superficiality, and well-meaning generalizations through a commitment to high-quality research, thoughtful analysis of mental health issues, and high professional standards of practice in all areas of mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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- 2024
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6. Vital Signs for Pediatric Health: High School Graduation.
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Hoagwood K, Walker DK, Edwards A, Kaminski JW, Kelleher KJ, Spandorfer J, and Fox EG
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Competing Interests: Conflict-of-Interest Disclosures: Erin Fox discloses employment by the National Academies of Sciences, Engineering, and Medicine while this paper series was being drafted.
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- 2023
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7. Vital Signs for Pediatric Health: Infant Mortality.
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Kelleher KJ, Hoagwood K, Walker DK, Kaminski JW, Gardner W, and Fox EG
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Competing Interests: Conflict-of-Interest Disclosures: Erin Fox discloses employment by the National Academies of Sciences, Engineering, and Medicine while this paper series was being drafted.
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- 2023
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8. Family Engagement at the Systems Level: A Framework for Action.
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Dworetzky B, Hoover CG, and Walker DK
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- Humans, Family, Delivery of Health Care
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While family engagement at the individual level of health care, such as families partnering with providers in decision-making about health care for an individual child has been well studied, family engagement in systems-level activities (e.g., participation in advisory and other decision-making groups, or creation and revision of policies) that impact the health services families and children receive has not. This note from the field presents a framework that describes the information and supports that help families partner with professionals and contribute to systems-level activities. Without attention to these components of family engagement, family presence and participation may be only token. We engaged an expert Family/Professional Workgroup whose members represented key constituencies and diverse geography, race/ethnicity, and areas of expertise; conducted a review of peer-reviewed publications and grey literature; and conducted a series of key informant interviews to identify best practices for supporting meaningful family engagement at the systems level. Based on an analysis of the findings, the authors identified four action-oriented domains of family engagement and key criteria that support and strengthen meaningful family engagement in systems-level initiatives. Child- and family-serving serving organizations can use this Family Engagement in Systems framework to support meaningful family engagement in the design of policies, practices, services, supports, quality improvement projects, research, and other systems-level activities., (© 2023. The Author(s).)
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- 2023
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9. Allergen Immunotherapy Enhances Airway Epithelial Antiviral Immunity in Patients with Allergic Asthma (VITAL Study): A Double-Blind Randomized Controlled Trial.
- Author
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Woehlk C, Ramu S, Sverrild A, Nieto-Fontarigo JJ, Vázquez-Mera S, Cerps S, Pulga A, Andreasson LM, Eriksen LL, Dyhre-Petersen N, Menzel M, Klein DK, Hansen S, Uller L, and Porsbjerg C
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- Adult, Animals, Humans, Pyroglyphidae, Antiviral Agents therapeutic use, Desensitization, Immunologic methods, Antigens, Dermatophagoides, Treatment Outcome, Tumor Necrosis Factor-alpha, Poly C therapeutic use, Allergens, Asthma drug therapy, Rhinitis, Allergic drug therapy
- Abstract
Rationale: Allergic asthma is linked to impaired bronchial epithelial secretion of IFNs, which may be causally linked to the increased risk of viral exacerbations. We have previously shown that allergen immunotherapy (AIT) effectively reduces asthma exacerbations and prevents respiratory infections requiring antibiotics; however, whether AIT alters antiviral immunity is still unknown. Objectives: To investigate the effect of house dust mite sublingual AIT (HDM-SLIT) on bronchial epithelial antiviral and inflammatory responses in patients with allergic asthma. Methods: In this double-blind, randomized controlled trial (VITAL [The Effect of Allergen Immunotherapy on Anti-viral Immunity in Patients with Allergic Asthma]), adult patients with HDM allergic asthma received HDM-SLIT 12-SQ or placebo for 24 weeks. Bronchoscopy was performed at baseline and at Week 24, which included sampling for human bronchial epithelial cells. Human bronchial epithelial cells were cultured at baseline and at Week 24 and stimulated with the viral mimic polyinosinic:polycytidylic acid (poly(I:C)). mRNA expression was quantified using qRT-PCR, and protein concentrations were measured using multiplex ELISA. Measurements and Main Results: Thirty-nine patients were randomized to HDM-SLIT ( n = 20) or placebo ( n = 19). HDM-SLIT resulted in increased polyinosinic:polycytidylic acid-induced expression of IFN-β at both the gene ( P = 0.009) and protein ( P = 0.02) levels. IFN-λ gene expression was also increased ( P = 0.03), whereas IL-33 tended to be decreased ( P = 0.09). On the other hand, proinflammatory cytokines IL-6 ( P = 0.009) and TNF-α (tumor necrosis factor-α) ( P = 0.08) increased compared with baseline in the HDM-SLIT group. There were no significant changes in TSLP (thymic stromal lymphopoietin), IL-4, IL-13, and IL-10. Conclusions: HDM-SLIT improves bronchial epithelial antiviral resistance to viral infection. These results potentially explain the efficacy of HDM-SLIT in reducing exacerbations in allergic asthma. Clinical trial registered with www.clinicaltrials.gov (NCT04100902).
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- 2023
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10. Distribution of type 2 biomarkers and association with severity, clinical characteristics and comorbidities in the BREATHE real-life asthma population.
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Frøssing L, Klein DK, Hvidtfeldt M, Obling N, Telg G, Erjefält JS, Bodtger U, and Porsbjerg C
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Background: Type 2 (T2) high asthma is recognised as a heterogenous entity consisting of several endotypes; however, the prevalence and distribution of the T2 biomarkers in the general asthma population, across asthma severity, and across compartments is largely unknown. The objective of the present study was to describe expression and overlaps of airway and systemic T2 biomarkers in a clinically representative asthma population., Methods: Patients with asthma from the real-life BREATHE cohort referred to a specialist centre were included and grouped according to T2 biomarkers: blood and sputum eosinophilia (≥0.3×10
9 cells·L-1 and 3% respectively), total IgE (≥150 U·mL-1 ), and fractional exhaled nitric oxide (≥25 ppb)., Results: Patients with mild-to-moderate asthma were younger (41 versus 49 years, p<0.001), had lower body mass index (25.9 versus 28.0 kg·m-2 , p=0.002) and less atopy (47% versus 58%, p=0.05), higher forced expiratory volume in 1 s (3.2 versus 2.8 L, p<0.001) and forced vital capacity (4.3 versus 3.9 L, p<0.001) compared with patients with severe asthma, who had higher blood (0.22×109 versus 0.17×109 cells·L-1 , p=0.01) and sputum (3.0% versus 1.5%, p=0.01) eosinophils. Co-expression of all T2 biomarkers was a particular characteristic of severe asthma (p<0.001). In patients with eosinophilia, sputum eosinophilia without blood eosinophilia was present in 45% of patients with mild-to-moderate asthma and 35% with severe asthma., Conclusion: Severe asthma is more commonly associated with activation of several T2 pathways, indicating that treatments targeting severe asthma may need to act more broadly on T2 inflammatory pathways. Implementation of airway inflammometry in clinical care is of paramount importance, as the best treatable trait is otherwise is overlooked in a large proportion of patients irrespective of disease severity., Competing Interests: Conflicts of interest: L. Frøssing, D.K. Klein, N. Obling, J.S. Erjefält and U. Bodtger report no conflicts of interest in relation to the current manuscript. M. Hvidtfeldt and C. Porsbjerg report unrestricted grants from Teva and AstraZeneca. G. Telg is employed by AstraZeneca Nordic., (Copyright ©The authors 2023.)- Published
- 2023
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11. Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma.
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Klein DK, Silberbrandt A, Frøssing L, Hvidtfeldt M, von Bülow A, Nair P, Mukherjee M, and Porsbjerg C
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- Autoantibodies, Autoimmunity, Eosinophil Peroxidase, Eosinophils, Humans, Inflammation, Leukocyte Count, Prednisolone, Smoking adverse effects, Sputum, Asthma, Pulmonary Eosinophilia
- Abstract
Introduction: Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids. Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear., Objective: To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness., Methods: Patients with severe asthma according to European Respiratory Society/American Thoracic Society criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-week course of prednisolone., Results: 132 severe asthmatics were included in the study. 39 (29.5%) patients had ≥10 pack-years of smoking history: 36 (27.3%) were former smokers and three (2.3%) current smokers; and 93 (70.5%) had <10 pack-years exposure. Eosinophilic airway inflammation was more prevalent among patients with ≥10 pack-years (66.7%), compared to patients with <10 pack-years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO (p<0.05 and p<0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a ≥10 pack-year smoking history., Conclusion: In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation and relative insensitivity to steroids, as well as airway autoimmunity., Competing Interests: Conflict of interest: D.K. Klein declares no competing interests. A. Silberbrandt declares no competing interests. L. Frøssing declares payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline, in the 36 months prior to manuscript submission. M. Hvidtfeldt declares no competing interests. A. von Bülow declares grants from Novartis Healthcare, Denmark; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Novartis; and participation on a data safety monitoring board or advisory board for Novartis, all in the 36 months prior to manuscript submission. P. Nair reports grants and personal fees from AstraZeneca, grants from Novartis, grants and personal fees from Teva, grants from Sanofi, grants and personal fees from Roche, personal fees from Novartis, personal fees from Merck, personal fees from Equillium, grants from Foresee, outside the submitted work. M. Mukherjee reports grants from Canadian Institutes of Health Research, grants from Methapharm Specialty Pharmaceuticals, personal fees from AstraZeneca, personal fees from GlaxoSmithKline, outside the submitted work. C. Porsbjerg declares grants, consulting fees and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK, all in the 36 months prior to manuscript submission., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)
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- 2022
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12. A Review of the Maternal and Child Health APHA Policy Statements, 1970-2019.
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Payton C, Mishkin K, Davis CA, Katzburg J, and Walker DK
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Introduction: The American Public Health Association (APHA) policy statements are written by members and approved by the APHA Governing Council. Policy statements inform APHA's position on key public health issues. Maternal and child health (MCH) is a broad discipline focused on health issues concerning women, children, youth, and families. APHA's MCH policies from the last 50 years were reviewed in celebration of the 100th anniversary of the MCH Section of APHA., Methods: A cross-sectional design was utilized to identify MCH-related statements within the larger APHA policy statement database from 1970 to 2019 (N = 1,110). The policy statements were coded as primary MCH (main focus was MCH) or secondary MCH (mentioned MCH subpopulations as vulnerable population). The primary MCH themes were also identified., Results: 545 (49%) of the APHA policy statements were related to MCH, including 226 (20%) coded as primary MCH and 319 (29%) secondary MCH. The primary MCH policy statements had a main focus on the following subpopulations: women (44%), children (33%), adolescents/young adults (15%), infants (12%), families (5%), and men (2%). Major themes included reproductive health/family planning, school health, children's health, pregnancy/childbirth, and breastfeeding/nutrition., Conclusions: MCH policy statements remained an important part of APHA's policy and advocacy focus over time as indicated through the continuous high number and proportion of MCH policy statements. The historical overview of MCH policy provides insight into critical policy issues confronting the MCH field over the decades and provides guidance for future policy initiatives including a need for increased emphasis on diverse MCH populations., Significance: This analysis provides a 50 year overview of MCH themes as viewed by the policy statements published by APHA, the largest public health professional organization in the United States. These policy statements represent the cutting edge of MCH policy efforts and were written to influence national, state, and local public health policy. APHA policy statements should continue to address these important MCH topics in the future with an increased emphasis on diverse MCH populations. APHA policy making is a valuable national professional activity for the MCH field with the goal of improving the health for MCH communities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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13. Detecting immunoglobulins in processed sputa.
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Cass SP, McGrath JJC, Son K, Radford K, LaVigne N, Klein DK, Ditlev SB, Porsbjerg C, Nair P, Stampfli MR, and Mukherjee M
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- Humans, Immunologic Tests, Immunoglobulins, Sputum
- Published
- 2021
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14. Parenting and social determinants of health.
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Walker DK
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- Child, Cognition, Emotions, Humans, Residence Characteristics, Parenting, Social Determinants of Health
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Social determinants of health is a concept relevant to parenting in two ways. First, parenting behavior is a social determinant for child health and development; effective parenting is essential for successful emotional, physical and cognitive development. Second, social determinants of health are critical to the development and sustainability of adequate parenting behaviors, which, in term, are a social determinant of child health. Key social determinants related to parenting include economic stability, education, social and community context, neighborhood and built environment, access to health care and parenting interventions, and racism., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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15. Systematic monitoring of glanders-infected horses by complement fixation test, bacterial isolation, and PCR.
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Abreu DC, Gomes AS, Tessler DK, Chiebao DP, Fava CD, Romaldini AHCN, Araujo MC, Pompei J, Marques GF, Harakava R, Pituco EM, and Nassar AFC
- Abstract
Glanders is an equine zoonosis caused by Burkholderia mallei that is responsible for considerable economic loss. Complement fixation testing (CFT) using warm or cold incubation are recommended by the OIE, but many routinely used detection tests may present misleading results. To increase accuracy of glanders diagnosis and establish an appropriate protocol in collaboration with the National Equine Health Program, seven horses positive for glanders kept in isolation in Brazil were examined fortnightly by CFT, microbiological screening, and molecular testing. Warm and cold serologies with USDA and c.c.Pro antigens, respectively, were performed on 132 samples using the US Department of Agriculture protocol . The warm and cold serologies showed, respectively,12.9% and 17.3% seroreactive, 85.7% and 65.2% non-reactive, 0.8% and 3% inconclusive, and 0% and 2.3% anticomplementary. The agreement of CFT protocols was moderate. Of 213 clinical samples submitted to selective culture (167 nasal swabs, 5 ocular swabs, 3 lymph node punctures, and 38 tissue samples from four horses that died), 1.9% tested positive for B. mallei. Fourteen samples and one nasal swab (7%) tested positive with PCR. Cold CFT with the USDA and c.c.Pro antigens, in combination with PCR to increase sensitivity, may be useful for diagnosis of chronic glanders., Competing Interests: We are submitting the paper entitled “Systematic monitoring of glanders-infected horses by complement fixation test, bacterial isolation, and PCR “ for analysis by the editorial boarding of the Veterinary and Animal Science. We declare that there is no financial or personal relationship that could cause a conflict of interest regarding this article., (© 2020 The Authors. Published by Elsevier Ltd.)
- Published
- 2020
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16. Counting Children in the U.S. 2020 Census: Assure Our Future is Represented.
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Seltzer JA and Walker DK
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Competing Interests: Conflict-of-Interest Disclosures: None to disclose.
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- 2020
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17. Clinical characteristics of the BREATHE cohort - a real-life study on patients with asthma and COPD.
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Backer V, Klein DK, Bodtger U, Romberg K, Porsbjerg C, Erjefält JS, Kristiansen K, Xu R, Silberbrandt A, Frøssing L, Hvidtfeldt M, Obling N, Jarenbäck L, Nasr A, Tufvesson E, Mori M, Winther-Jensen M, Karlsson L, Nihlén U, Veje Flintegaard T, and Bjermer L
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Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)
- Published
- 2020
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18. Scaling up Evidence-Based Interventions in US Public Systems to Prevent Behavioral Health Problems: Challenges and Opportunities.
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Fagan AA, Bumbarger BK, Barth RP, Bradshaw CP, Cooper BR, Supplee LH, and Walker DK
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- Adolescent, Child, Child Health Services organization & administration, Health Services Research organization & administration, Humans, Program Evaluation, Public Health, United States, Child Behavior Disorders prevention & control, Community Health Services organization & administration, Evidence-Based Medicine methods, Health Planning Organizations organization & administration
- Abstract
A number of programs, policies, and practices have been tested using rigorous scientific methods and shown to prevent behavioral health problems (Catalano et al., Lancet 379:1653-1664, 2012; National Research Council and Institute of Medicine, 2009). Yet these evidence-based interventions (EBIs) are not widely used in public systems, and they have limited reach (Glasgow et al., American Journal of Public Health 102:1274-1281, 2012; National Research Council and Institute of Medicine 2009; Prinz and Sanders, Clinical Psychology Review 27:739-749, 2007). To address this challenge and improve public health and well-being at a population level, the Society for Prevention Research (SPR) formed the Mapping Advances in Prevention Science (MAPS) IV Translation Research Task Force, which considered ways to scale up EBIs in five public systems: behavioral health, child welfare, education, juvenile justice, and public health. After reviewing other efforts to scale up EBIs in public systems, a common set of factors were identified as affecting scale-up in all five systems. The most important factor was the degree to which these systems enacted public policies (i.e., statutes, regulations, and guidance) requiring or recommending EBIs and provided public funds for EBIs. Across systems, other facilitators of scale-up were creating EBIs that are ready for scale-up, public awareness of and support for EBIs, community engagement and capacity to implement EBIs, leadership support for EBIs, a skilled workforce capable of delivering EBIs, and data monitoring and evaluation capacity. It was concluded that the following actions are needed to significantly increase EBI scale-up in public systems: (1) provide more public policies and funding to support the creation, testing, and scaling up of EBIs; (2) develop and evaluate specific frameworks that address systems level barriers impeding EBI scale-up; and (3) promote public support for EBIs, community capacity to implement EBIs at scale, and partnerships between community stakeholders, policy makers, practitioners, and scientists within and across systems.
- Published
- 2019
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19. Global mental health: A call to action.
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Gil-Rivas V, Handrup CT, Tanner E, and Walker DK
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- Health Services Accessibility, Humans, Psychiatry, Refugees psychology, Stress, Psychological psychology, Global Health, Health Promotion, Mental Disorders diagnosis, Mental Disorders therapy, Mental Health
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Mental health needs have been recognized as a priority area by the World Health Organization (WHO), and a Comprehensive Mental Health Action Plan (2013) was proposed to address the needs of millions of people around the world. Concerns have been raised about the degree to which current global efforts are appropriate and sufficient for promoting mental health (MH), reducing the risk for common MH disorders, and addressing the needs of individuals experiencing mental illness. This commentary expands on the presentation of the Global Alliance for Behavioral Health and Social Justice's Task Force on Global Mental Health at the 16th Biennial Conference of the Society for Community Research and Action, held in Ottawa, Ontario, Canada June 21-24, 2017, "Building Capacity to Address Mental Illness and Emotional Distress in Low-Resource Settings and Among Refugee Populations." Utilizing a socioecological framework, this commentary offers a call to action in addressing global mental health by emphasizing the need for greater investments in wellness promotion, prevention, treatment, and recovery. Importantly, such efforts need to value local knowledge and culture, harness natural existing resources and assets, and ensure equitable distribution of key resources for MH. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
- Published
- 2019
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20. Applying Collaborative Learning and Quality Improvement to Public Health: Lessons from the Collaborative Improvement and Innovation Network (CoIIN) to Reduce Infant Mortality.
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Ghandour RM, Flaherty K, Hirai A, Lee V, Walker DK, and Lu MC
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- Humans, Infant, Program Evaluation, Public Health, Infant Mortality, Interdisciplinary Placement, Organizational Innovation, Quality Improvement
- Abstract
Objectives: Infant mortality remains a significant public health problem in the U.S. The Collaborative Improvement & Innovation Network (CoIIN) model is an innovative approach, using the science of quality improvement and collaborative learning, which was applied across 13 Southern states in Public Health Regions IV and VI to reduce infant mortality and improve birth outcomes. We provide an in-depth discussion of the history, development, implementation, and adaptation of the model based on the experience of the original CoIIN organizers and participants. In addition to the political genesis and functional components of the initiative, 8 key lessons related to staffing, planning, and implementing future CoIINs are described in detail., Methods: This paper reports the findings from a process evaluation of the model. Data on the states' progress toward reducing infant mortality and improving birth outcomes were collected through a survey in the final months of a 24-month implementation period, as well as through ongoing team communications., Results: The peer-to-peer exchange and platform for collaborative learning, as well as the sharing of data across the states, were major strengths and form the foundation for future CoIIN efforts. A lasting legacy of the initiative is the unique application and sharing of provisional "real time" data to inform "real time" decision-making., Conclusion: The CoIIN model of collaborative learning, QI, and innovation offers a promising approach to strengthening partnerships within and across states, bolstering data systems to inform and track progress more rapidly, and ultimately accelerating improvement toward healthier communities, States, and the Nation as a whole.
- Published
- 2017
- Full Text
- View/download PDF
21. Continuing our organizational mission: A new name for a new time.
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Walker DK, Kilmer RP, and Armstrong MI
- Subjects
- Humans, Mental Health Services, Social Justice, Health Behavior, Organizational Objectives, Psychiatry
- Abstract
This editorial explains the need for a new name for the American Orthopsychiatric Association (ORTHO). As ORTHO continues their work into the 21st century, they want to better reflect their global membership and focus, increasing the number of partnerships with individuals and organizations, and commitment to a just society. Therefore, ORTHO is changing their name to the Global Alliance for Behavioral Health and Social Justice. It is crucial to underscore that, although the organizations name is changing, the values and principles that inform their work will remain the same. The mission statement of the Global Alliance for Behavioral Health and Social Justice is "to inform policy, practice, and research to prevent behavioral health disorders and to promote conditions to ensure that people with disorders can be full participants in society." (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)
- Published
- 2017
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22. Impacts of a farmers' market incentive programme on fruit and vegetable access, purchase and consumption.
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Olsho LE, Payne GH, Walker DK, Baronberg S, Jernigan J, and Abrami A
- Subjects
- Awareness, Choice Behavior, Farmers, Female, Food Preferences, Fruit, Health Behavior, Health Promotion, Health Surveys, Humans, Male, Middle Aged, Motivation, New York City, Vegetables, Agriculture, Diet, Feeding Behavior, Food Supply, Poverty, Program Evaluation, Small Business
- Abstract
Objective: The present study examines the impact of Health Bucks, a farmers' market incentive programme, on awareness of and access to farmers' markets, and fruit and vegetable purchase and consumption in low-income New York City neighbourhoods., Design: The evaluation used two primary data collection methods: (i) an on-site point-of-purchase survey of farmers' market shoppers; and (ii) a random-digit-dial telephone survey of residents in neighbourhoods where the programme operates. Additionally, we conducted a quasi-experimental analysis examining differential time trends in consumption before and after programme introduction using secondary Community Health Survey (CHS) data., Setting: New York City farmers' markets and communities., Subjects: Farmers' market shoppers (n 2287) completing point-of-purchase surveys in a representative sample of New York City farmers' markets in 2010; residents (n 1025) completing random-digit-dial telephone survey interviews in 2010; and respondents (n 35 606) completing CHS interviews in 2002, 2004, 2008 and 2009., Results: Greater Health Bucks exposure was associated with: (i) greater awareness of farmers' markets; (ii) increased frequency and amount of farmers' market purchases; and (iii) greater likelihood of a self-reported year-over-year increase in fruit and vegetable consumption. However, our CHS analysis did not detect impacts on consumption., Conclusions: While our study provides promising evidence that use of farmers' market incentives is associated with increased awareness and use of farmers' markets, additional research is needed to better understand impacts on fruit and vegetable consumption.
- Published
- 2015
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- View/download PDF
23. Selected findings from the cross-site evaluation of the Federal Healthy Start Program.
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Drayton VL, Walker DK, Ball SW, Donahue SM, and Fink RV
- Subjects
- Child, Child Health, Child Health Services standards, Child, Preschool, Female, Humans, Infant, Infant Mortality, Infant, Newborn, Maternal-Child Health Services organization & administration, Pregnancy, Pregnancy Complications prevention & control, Pregnancy Outcome, Prenatal Care standards, Program Evaluation, United States, Healthy People Programs organization & administration, Healthy People Programs standards, Maternal-Child Health Services standards
- Abstract
Initiated in 1991, the Federal Healthy Start Program includes 105 community-based projects in 39 states, the District of Columbia and Puerto Rico. Healthy Start projects work collaboratively with stakeholders to ensure participants' continuity of care during pregnancy through 2 years postpartum. This evaluation of Healthy Start projects examined relationships between implementation of nine core service and system program components and improvements in birth and project outcomes. Program components and outcomes were examined using data from a 2010 Healthy Start project director (PD) survey (N = 104 projects) and 2009 performance measure data from the Maternal and Child Health Bureau Discretionary Grant Information System (N = 98 projects). We explored bivariate relationships between the nine core program components and (a) intermediate and long-term project outcomes and (b) birth outcomes. We assessed independent associations of implementation of all core program components with birth outcomes, adjusting for project characteristics and activities. In 2010, 57 projects implemented all nine core program components: 104 implemented all five core service components and 69 implemented all four core systems components. Implementation of all core program components was significantly associated with several PD-reported intermediate and long-term project outcomes, but was not associated with singleton low birth weight or infant mortality among participants' infants. This evaluation revealed a mixed set of relationships between Healthy Start projects' implementation of the core program components and achievement of project outcomes. Although the findings demonstrated a positive impact of Healthy Start projects on birth outcomes, only a few associations were statistically significant.
- Published
- 2015
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- View/download PDF
24. Persons with disabilities as an unrecognized health disparity population.
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Krahn GL, Walker DK, and Correa-De-Araujo R
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- Adolescent, Adult, Aged, Aged, 80 and over, Crime Victims statistics & numerical data, Environment, Health Behavior, Health Services Accessibility organization & administration, Humans, Middle Aged, Prejudice, Socioeconomic Factors, Transition to Adult Care organization & administration, Young Adult, Disabled Persons, Health Status Disparities, Public Health Administration
- Abstract
Disability is an emerging field within public health; people with significant disabilities account for more than 12% of the US population. Disparity status for this group would allow federal and state governments to actively work to reduce inequities. We summarize the evidence and recommend that observed differences are sufficient to meet the criteria for health disparities: population-level differences in health outcomes that are related to a history of wide-ranging disadvantages, which are avoidable and not primarily caused by the underlying disability. We recommend future research and policy directions to address health inequities for individuals with disabilities; these include improved access to health care and human services, increased data to support decision-making, strengthened health and human services workforce capacity, explicit inclusion of disability in public health programs, and increased emergency preparedness.
- Published
- 2015
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- View/download PDF
25. Atrioventricular block in coronary artery bypass surgery: perioperative predictors and impact on mortality.
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Piantá RM, Ferrari AD, Heck AA, Ferreira DK, Piccoli Jda C, Albuquerque LC, Guaragna JC, and Petracco JB
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- Age Factors, Cardiopulmonary Bypass adverse effects, Epidemiologic Methods, Female, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Pacemaker, Artificial, Perioperative Period adverse effects, Perioperative Period mortality, Risk Factors, Sex Factors, Time Factors, Treatment Outcome, Atrioventricular Block etiology, Atrioventricular Block mortality, Coronary Artery Bypass adverse effects, Coronary Artery Bypass mortality, Hospital Mortality, Postoperative Complications mortality
- Abstract
Introduction: Disturbances of the cardiac conduction system are frequent in the postoperative period of coronary artery bypass surgery. They are mostly reversible and associated with some injury of the conduction tissue, caused by the ischemic heart disease itself or by perioperative factors., Objective: Primary: investigate the association between perioperative factors and the emergence of atrioventricular block in the postoperative period of coronary artery bypass surgery. Secondary: determine the need for temporary pacing and of a permanent pacemaker in the postoperative period of coronary artery bypass surgery and the impact on hospital stay and hospital mortality., Methods: Analysis of a retrospective cohort of patients submitted to coronary artery bypass surgery from the database of the Postoperative Heart Surgery Unit of the Sao Lucas Hospital of the Pontifical Catholic University of Rio Grande do Sul, using the logistic regression method., Results: In the period from January 1996 to December 2012, 3532 coronary artery bypass surgery were carried out. Two hundred and eighty-eight (8.15% of the total sample) patients had atrioventricular block during the postoperative period of coronary artery bypass surgery, requiring temporary pacing. Eight of those who had atrioventricular block progressed to implantation of a permanent pacemaker (0.23% of the total sample). Multivariate analysis revealed a significant association of atrioventricular block with age above 60 years (OR=2.34; CI 95% 1.75-3.12; P<0.0001), female gender (OR=1.37; CI 95% 1.06-1.77; P=0.015), chronic kidney disease (OR=2.05; CI 95% 1.49-2.81; P<0.0001), atrial fibrillation (OR=2.06; CI 95% 1.16-3.66; P=0.014), functional class III and IV of the New York Heart Association (OR=1.43; CI 95% 1.03-1.98; P=0.031), perioperative acute myocardial infarction (OR=1.70; CI 95% 1.26-2.29; P<0.0001) and with the use of the intra-aortic balloon in the postoperative period of coronary artery bypass surgery (OR=1.92; CI 95% 1.21-3.05; P=0.006). The presence of atrioventricular block resulted in a significant increase in mortality (17.9% vs. 7.3% in those who did not develop atrioventricular block) (OR=2.09; CI 95% 1.46-2.99; P<0.0001) and a longer hospital stay (12.75 days x 10.53 days for those who didn't develop atrioventricular block) (OR=1.01; CI 95% 1.00-1.02; P=0.01)., Conclusions: In most cases, atrioventricular block in the postoperative period of coronary artery bypass surgery is transient and associated with several perioperative factors: age above 60 years, female sex, chronic kidney disease, atrial fibrillation, New York Heart Association functional class III or IV, perioperative acute myocardial infarction and use of an intra-aortic balloon. Its occurrence prolongs hospitalization and, above all, doubles the risk of mortality.
- Published
- 2015
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26. Introduction to the Special Issue on Leadership Development for the MCH Workforce.
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Fernandez C, Kavanagh L, and Walker DK
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- Humans, Staff Development, United States, Leadership, Maternal-Child Health Centers organization & administration, Periodicals as Topic
- Published
- 2015
- Full Text
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27. Family leaders and workforce leadership development.
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Reynolds MC, Birzer M, St John J, Wells N, Anderson B, and Walker DK
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- Adult, Child, Preschool, Female, Humans, Male, Patient Advocacy, Program Development, Program Evaluation, Staff Development, United States, Family, Health Workforce organization & administration, Leadership, Maternal-Child Health Centers organization & administration
- Published
- 2015
- Full Text
- View/download PDF
28. Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control.
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Klein DK, Hoffmann S, Ahlskog JK, O'Hanlon K, Quaas M, Larsen BD, Rolland B, Rösner HI, Walter D, Kousholt AN, Menzel T, Lees M, Johansen JV, Rappsilber J, Engeland K, and Sørensen CS
- Subjects
- Cell Line, Tumor, DNA Primers genetics, Flow Cytometry, Fluorescent Antibody Technique, HEK293 Cells, Humans, Immunoblotting, Immunoprecipitation, Luciferases, Mutagenesis, Site-Directed, RNA Interference, RNA, Small Interfering genetics, Ubiquitination, Cell Cycle Checkpoints physiology, Cell Cycle Proteins metabolism, Cyclins metabolism, DNA Repair physiology, Trans-Activators metabolism
- Abstract
Cells respond to DNA damage by activating cell cycle checkpoints to delay proliferation and facilitate DNA repair. Here, to uncover new checkpoint regulators, we perform RNA interference screening targeting genes involved in ubiquitylation processes. We show that the F-box protein cyclin F plays an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein cyclin F with suppression of the B-Myb/cyclin A pathway to ensure a DNA damage-induced checkpoint response in G2.
- Published
- 2015
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29. Implementing a farmers' market incentive program: perspectives on the New York City Health Bucks Program.
- Author
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Payne GH, Wethington H, Olsho L, Jernigan J, Farris R, and Walker DK
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- Commerce, Crops, Agricultural supply & distribution, Fruit economics, Fruit supply & distribution, Humans, New York City, Poverty, Program Evaluation, Vegetables economics, Vegetables supply & distribution, Crops, Agricultural economics, Food Supply economics, Health Promotion economics
- Abstract
Introduction: One strategy for lowering the prevalence of obesity is to increase access to and affordability of fruits and vegetables through farmers' markets. However, little has been documented in the literature on the implementation of such efforts. To address this gap, the Division of Nutrition, Physical Activity, and Obesity (DNPAO) sponsored an evaluation of the New York City Health Bucks program, a farmers' market coupon incentive program intended to increase access to fresh fruits and vegetables in underserved neighborhoods while supporting local farmers., Methods: We conducted a process evaluation of Health Bucks program implementation. We interviewed 6 farmer/vendors, 3 market managers, and 4 program administrators, and collected data on site at 86 farmers' markets, including surveys of 81 managers and 141 farmer/vendors on their perspectives on promotion and redemption of the incentive coupons; knowledge and attitudes regarding the program; experiences with markets and products; and facilitators and barriers to program participation., Results: Results indicate that respondents view Health Bucks as a positive program model. Farmers' market incentive coupon programs like Health Bucks are one strategy to address the problem of obesity and were associated with higher fruit and vegetable access and purchases in low-income communities., Conclusions: This evaluation identified some areas for improving implementation of the Health Bucks program. Farmers' market incentive programs like Health Bucks may be one avenue to increase access to and affordability of fruits and vegetables among low-income persons. Further research is needed to assess the potential effects of these programs on access and health outcomes.
- Published
- 2013
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30. Potential influence of seasonal influenza vaccination requirement versus traditional vaccine promotion strategies on unvaccinated healthcare personnel.
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Thompson MG, McIntyre AF, Naleway AL, Black C, Kennedy ED, Ball S, Walker DK, Henkle EM, and Gaglani MJ
- Subjects
- Adult, Cohort Studies, Female, Humans, Male, Oregon, Prospective Studies, Self Report, Texas, Vaccination psychology, Washington, Attitude of Health Personnel, Health Personnel statistics & numerical data, Influenza Vaccines, Vaccination statistics & numerical data
- Abstract
In a prospective cohort study of 1670 healthcare personnel (HCP) providing direct patient care at Scott & White Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington, we examined the potential impact of twelve vaccine promotion strategies on the likelihood of being vaccinated. Internet-based surveys were conducted at enrollment (Fall, 2010) and at post-season (Spring, 2011), which asked HCP whether twelve vaccination promotion strategies would make them "much less" to "much more" likely to be vaccinated next season (on a 5-point Likert scale). Overall, 366 of 1670 HCP (22%) were unvaccinated. Half (50%) of unvaccinated HCP self-reported that a vaccination requirement would make them more likely to be vaccinated and most (62%) identified at least one strategy other than a vaccination requirement that would make them more likely to be vaccinated. In sub-groups of unvaccinated HCPs with specific barriers to vaccination, about one in three (range=27-35%) indicated that interventions targeting specific vaccination barrier would increase the likelihood they would be vaccinated. However, in all cases, significantly more unvaccinated HCP reported that a vaccination requirement would increase the likelihood of vaccination than reported a targeted intervention would have this effect (range in difference scores=+11-23%)., (Published by Elsevier Ltd.)
- Published
- 2013
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- View/download PDF
31. Achieving population health in accountable care organizations.
- Author
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Hacker K and Walker DK
- Subjects
- Accountable Care Organizations economics, Community Health Services, Cooperative Behavior, Delivery of Health Care, Integrated, Humans, Preventive Health Services, Public Health economics, Quality Assurance, Health Care, United States, Accountable Care Organizations standards, Public Health standards
- Abstract
Although "population health" is one of the Institute for Healthcare Improvement's Triple Aim goals, its relationship to accountable care organizations (ACOs) remains ill-defined and lacks clarity as to how the clinical delivery system intersects with the public health system. Although defining population health as "panel" management seems to be the default definition, we called for a broader "community health" definition that could improve relationships between clinical delivery and public health systems and health outcomes for communities. We discussed this broader definition and offered recommendations for linking ACOs with the public health system toward improving health for patients and their communities.
- Published
- 2013
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- View/download PDF
32. Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system.
- Author
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Newes-Adeyi G, Greece J, Bozeman S, Walker DK, Lewis F, and Gidudu J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Drug-Related Side Effects and Adverse Reactions epidemiology, Female, Humans, Male, Middle Aged, Young Adult, Adverse Drug Reaction Reporting Systems organization & administration, Influenza Vaccines administration & dosage, Influenza Vaccines adverse effects, Influenza, Human prevention & control
- Abstract
Objectives: We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings., Methods: We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website., Results: 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms., Conclusions: It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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33. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance.
- Author
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Menzel T, Nähse-Kumpf V, Kousholt AN, Klein DK, Lund-Andersen C, Lees M, Johansen JV, Syljuåsen RG, and Sørensen CS
- Subjects
- BRCA2 Protein genetics, Cell Line, DNA Damage, Fanconi Anemia Complementation Group N Protein, G2 Phase genetics, Gene Library, HCT116 Cells, HeLa Cells, Humans, Nuclear Proteins genetics, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Recombination, Genetic, Signal Transduction genetics, Tumor Suppressor Proteins genetics, BRCA2 Protein metabolism, G2 Phase physiology, High-Throughput Screening Assays, Nuclear Proteins metabolism, Tumor Suppressor Proteins metabolism
- Abstract
To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.
- Published
- 2011
- Full Text
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34. Atrioventricular block in the postoperative period of heart valve surgery: incidence, risk factors and hospital evolution.
- Author
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Ferrari AD, Süssenbach CP, Guaragna JC, Piccoli Jda C, Gazzoni GF, Ferreira DK, Albuquerque LC, and Goldani MA
- Subjects
- Aged, Atrioventricular Block etiology, Coronary Artery Bypass methods, Epidemiologic Methods, Female, Heart Valve Prosthesis Implantation methods, Heart Valve Prosthesis Implantation statistics & numerical data, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Perioperative Care, Aortic Valve surgery, Atrioventricular Block epidemiology, Cardiac Pacing, Artificial statistics & numerical data, Coronary Artery Bypass adverse effects, Heart Valve Prosthesis Implantation adverse effects, Mitral Valve surgery
- Abstract
Introduction: Disturbances of the cardiac conduction system are potential complications after cardiac valve surgery., Objectives: This study was designed to investigate the association between perioperative factors and atrio-ventricular block, the need for temporary cardiac artificial pacing and, if necessary, permanent pacemaker implantation after cardiac valve surgery., Methods: Retrospective analysis of the Cardiac Surgery Database - Hospital São Lucas/PUCRS. The data are collected prospectively and analyzed retrospectively., Results: Between January 1996 and December 2008 were included 1102 valve surgical procedures: 718 aortic valves (65.2%), 407 (36.9%) mitral valve and 190 (17.2%) coronar artery bypass grafting combined with valve repair and 23 (2.1%) aortic and mitral combined surgery. 187 patients (17%) showed clinical and electrocardiographic pattern of atrio-ventricular block requiring artificial temporary pacing. Of these, 14 patients (7.5%) required permanent pacemaker implantation (1.27% of the total valve surgery patients). Multivariate analysis showed association of the incidence of atrio-ventricular block and temporary pacing with mitral valve surgery (OR 1,76; CI 95% 1.08-2.37; P = 0.002), implantation of bioprosthetic devices (OR 1.59; CI 95% 1.02-3.91; P = 0,039), age over 60 years (OR 1.99; CI 95% 1.352.85; P < 0.001), prior use of anti-arrhythmic drugs (OR 1.86; CI 95% 1.04-3.14; P = 0.026) and previous use of b-blocker (OR 1.76; CI 95% 1.25-2.54; P = 0.002). Remarkably the presence of atrio-ventricular block did not significantly show association with increased mortality, but significantly prolonged (P < 0.0001) hospital length-of-stay and, therefore, hospital costs., Conclusions: Our study presents a group of predictive factors referring to a specific patient profile by which high risk of atrio-ventricular block and the need of temporary cardiac pacing after cardiac valve surgery it is determined.
- Published
- 2011
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35. Interleukin-6 release is higher across arm than leg muscles during whole-body exercise.
- Author
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Helge JW, Klein DK, Andersen TM, van Hall G, Calbet J, Boushel R, and Saltin B
- Subjects
- Adult, Arm physiology, Blood Glucose metabolism, Fatty Acids metabolism, Female, Glycogen metabolism, Humans, Lactates metabolism, Leg physiology, Male, Regional Blood Flow physiology, Young Adult, Exercise physiology, Interleukin-6 blood, Interleukin-6 metabolism, Muscle, Skeletal metabolism
- Abstract
Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen subjects (10 men and six women, with body mass index 24 ± 1 kg m(-2) and peak oxygen uptake 3.4 ± 0.6 l min(-1)) performed a 90 min combined arm and leg cycle exercise at 60% of maximal oxygen uptake. The subjects arrived at the laboratory having fasted overnight, and catheters were placed in the femoral artery and vein and in the subclavian vein. During exercise, arterial and venous limb blood was sampled and arm and leg blood flow were measured by thermodilution. Lean limb mass was measured by dual-energy X-ray absorbtiometry scanning. Before and after exercise, biopsies were obtained from vastus lateralis and deltoideus. During exercise, IL-6 release was similar between men and women and higher (P < 0.05) from arms than legs (1.01 ± 0.42 and 0.33 ± 0.12 ng min(-1) (kg lean limb mass)(-1), respectively). Blood flow (425 ± 36 and 554 ± 35 ml min(-1) (kg lean limb mass)(-1)) and fatty acid uptake (26 ± 7 and 47 ± 7 μmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 μmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P < 0.05). No correlations were present between IL-6 release and exogenous substrate uptakes. Muscle glycogen was similar in arms and legs before exercise (388 ± 22 and 428 ± 25 mmol (kg dry weight)(-1)), but after exercise it was only significantly lower in the leg (219 ± 29 mmol (kg dry weight)(-1)). The novel finding of a markedly higher IL-6 release from the exercising arm compared with the leg during whole-body exercise was not directly correlated to release or uptake of exogenous substrate, nor to muscle glycogen utilization.
- Published
- 2011
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36. Intermediate outcomes, strategies, and challenges of eight healthy start projects.
- Author
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Brand A, Walker DK, Hargreaves M, and Rosenbach M
- Subjects
- Case Management, Community Participation, Culture, Health Status Disparities, Humans, Infant, Infant, Newborn, Pilot Projects, Risk Assessment, United States, Health Education methods, Infant Mortality, Maternal Health Services organization & administration, Program Evaluation
- Abstract
Site visits were conducted for the evaluation of the national Healthy Start program to gain an understanding of how projects design and implement five service components (outreach, case management, health education, depression screening and interconceptional care) and four system components (consortium, coordination/collaboration, local health system action plan and sustainability) as well as program staff's perceptions of these components' influence on intermediate outcomes. Interviews with project directors, case managers, local evaluators, clinicians, consortium members, outreach/lay workers and other stakeholders were conducted during 3-day in-depth site visits with eight Healthy Start grantees. Grantees reported that both services and systems components were related to self-reported service achievements (e.g. earlier entry into prenatal care) and systems achievements (e.g. consumer involvement). Outreach, case management, and health education were perceived as the service components that contributed most to their achievements while consortia was perceived as the most influential systems component in reaching their goals. Furthermore, cultural competence and community voice were overarching project components that addressed racial/ethnic disparities. Finally, there was great variability across sites regarding the challenges they faced, with poor service availability and limited funding the two most frequently reported. Service provision and systems development are both critical for successful Healthy Start projects to achieve intermediate program outcomes. Unique contextual and community issues influence Healthy Start project design, implementation and reported accomplishments. All eight projects implement the required program components yet outreach, case management, and health education are cited most frequently for contributing to their perceived achievements.
- Published
- 2010
- Full Text
- View/download PDF
37. Characteristics, access, utilization, satisfaction, and outcomes of healthy start participants in eight sites.
- Author
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Rosenbach M, O'Neil S, Cook B, Trebino L, and Walker DK
- Subjects
- Adult, Child Health Services organization & administration, Consumer Behavior, Female, Health Services Accessibility organization & administration, Health Status, Healthy People Programs statistics & numerical data, Humans, Infant, Infant Mortality, Infant, Newborn, Male, Mothers, Outcome Assessment, Health Care, Perinatal Care statistics & numerical data, Postpartum Period, Pregnancy, Program Evaluation, Socioeconomic Factors, United States, Young Adult, Child Health Services statistics & numerical data, Health Services Accessibility statistics & numerical data, Healthy People Programs organization & administration, Perinatal Care organization & administration
- Abstract
To describe the characteristics, access, utilization, satisfaction, and outcomes of Healthy Start participants in eight selected sites, a survey of Healthy Start participants with infants ages 6-12-months-old at time of interview was conducted between October 2006 and January 2007. The response rate was 66% (n = 646), ranging from 37% in one site to >70% in seven sites. Healthy Start participants' outcomes were compared to two national benchmarks. Healthy Start participants reported that they were satisfied with the program (>90% on five measures). Level of unmet need was 6% or less for most services, except for dental appointments (11%), housing (13%), and child care (11%). Infants had significantly better access to medical care than did their mothers, with higher rates of insurance coverage, medical homes, and checkups, and fewer unmet needs for health care. Healthy Start participants' rates of ever breastfeeding (72%) and putting infants to sleep on their backs (70%) were at or near the Healthy People 2010 objectives, and considerably higher than rates among low-income mothers in the ECLS. The high rate of health education (>90%) may have contributed to these outcomes. Elimination of smoking among Healthy Start participants (46%) fell short of the Healthy People 2010 objective (99%). The low-birth weight (LBW) rate among Black Healthy Start participants (14%) was three times higher than the rate for Whites and Hispanics (5% each). Overall, the LBW rate in the eight sites (7.5%) was similar to the rate for low-income mothers in the ECLS, but both rates were above the Healthy People 2010 objective (5%). Challenges remain in reducing disparities in maternal and child health outcomes. Further attention to risk factors associated with LBW (especially smoking) may help close the gaps. The life course theory suggests that improved outcomes may require longer-term investments. Healthy Start's emerging focus on interconception care has the potential to address longer-term needs of participants.
- Published
- 2010
- Full Text
- View/download PDF
38. NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling.
- Author
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Sørensen CS, Melixetian M, Klein DK, and Helin K
- Subjects
- Cell Line, Tumor, Checkpoint Kinase 1, G2 Phase, Humans, Mitosis, Models, Biological, NIMA-Related Kinases, Neoplasms enzymology, Neoplasms pathology, Neoplasms therapy, Precancerous Conditions enzymology, Precancerous Conditions pathology, Cell Cycle, DNA Damage, Protein Kinases metabolism, Signal Transduction, cdc25 Phosphatases metabolism
- Abstract
The DNA damage induced G(2)/M checkpoint is an important guardian of the genome that prevents cell division when DNA lesions are present. The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator. CDC25A proteolysis is controlled by direct phosphorylation events that lead to its recognition by the ubiquitin ligase beta-TrCP. Recently we have identified NEK11, a member of NIMA-related kinase family, as the critical kinase triggering CDC25A degradation. NEK11 controls degradation of CDC25A by directly phosphorylating CDC25A on residues whose phosphorylation is required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. The activity of NEK11 is in turn controlled by CHK1 that activates NEK11 via phosphorylation on serine 273. Since inhibition of NEK11 activity forces checkpoint-arrested cells into mitosis and cell death, NEK11 is, like CHK1, a strong candidate target for the development of novel anticancer drugs. Here we further support this notion by showing results suggesting that NEK11 expression increases during colon cancer development.
- Published
- 2010
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39. Research Consortium on Children with Chronic Conditions (RCCCC): a vehicle for interdisciplinary collaborative research.
- Author
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Pless IB, Stein RE, and Walker DK
- Subjects
- Child, Health Services Needs and Demand, Humans, Child Welfare, Chronic Disease, Cooperative Behavior, Interdisciplinary Communication, Research Design
- Abstract
To describe the evolution, accomplishments, and limitations of a research consortium after 25 years of existence. A narrative historical account supplemented by data documenting citations to all group papers. In 1980 the Research Consortium on Children with Chronic Conditions was established. Since then, we have met 2-3 times a year to discuss issues related to research and policies for children with special health care needs. We describe the origin of the Consortium, its operation, and some of its accomplishments, as well as the difficulties it encountered. Our interactions helped promote and sustain research on an emerging topic and did so in an interdisciplinary manner. We include a citation analysis suggesting that group papers published by Consortium members are reasonably well cited by others. We believe our work has been of value in developing influencing research, clinical practice, and policy. This paper is intended to serve as a guide for others who believe that this type of interaction can do much to promote an emerging field. However, it also highlights some of the difficulties in forging and maintaining a productive, research-focused relationship over an extended period of time. The most important lesson learned is that a small group of committed individuals able to meet on a regular basis can accelerate movement in a new field. However, unless stable funding can be secured, maintaining a consortium is truly challenging.
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- 2010
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40. Dysregulation of glycogen synthase COOH- and NH2-terminal phosphorylation by insulin in obesity and type 2 diabetes mellitus.
- Author
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Højlund K, Birk JB, Klein DK, Levin K, Rose AJ, Hansen BF, Nielsen JN, Beck-Nielsen H, and Wojtaszewski JF
- Subjects
- Adenosine Monophosphate physiology, Blotting, Western, Calcium physiology, Female, Glucose metabolism, Glucose Tolerance Test, Homeostasis, Humans, Kinetics, Male, Middle Aged, Muscle, Skeletal enzymology, Phosphoric Monoester Hydrolases metabolism, Phosphorylation, Reference Values, Signal Transduction, Diabetes Mellitus, Type 2 enzymology, Glycogen Synthase antagonists & inhibitors, Insulin pharmacology, Obesity enzymology
- Abstract
Context: Insulin-stimulated glucose disposal is impaired in obesity and type 2 diabetes mellitus (T2DM) and is tightly linked to impaired skeletal muscle glucose uptake and storage. Impaired activation of glycogen synthase (GS) by insulin is a well-established defect in both obesity and T2DM, but the underlying mechanisms remain unclear., Design and Participants: Insulin action was investigated in a matched cohort of lean healthy, obese nondiabetic, and obese type 2 diabetic subjects by the euglycemic-hyperinsulinemic clamp technique combined with muscle biopsies. Activity, site-specific phosphorylation, and upstream signaling of GS were evaluated in skeletal muscle., Results: GS activity correlated inversely with phosphorylation of GS site 2+2a and 3a. Insulin significantly decreased 2+2a phosphorylation in lean subjects only and induced a larger dephosphorylation at site 3 in lean compared with obese subjects. The exaggerated insulin resistance in T2DM compared with obese subjects was not reflected by differences in site 3 phosphorylation but was accompanied by a significantly higher site 1b phosphorylation during insulin stimulation. Hyperphosphorylation of another Ca(2+)/calmodulin-dependent kinase-II target, phospholamban-Thr17, was also evident in T2DM. Dephosphorylation of GS by phosphatase treatment fully restored GS activity in all groups., Conclusions: Dysregulation of GS phosphorylation plays a major role in impaired insulin regulation of GS in obesity and T2DM. In obesity, independent of T2DM, this is associated with impaired regulation of site 2+2a and likely site 3, whereas the exaggerated insulin resistance to activate GS in T2DM is linked to hyperphosphorylation of at least site 1b. Thus, T2DM per se seems unrelated to defects in the glycogen synthase kinase-3 regulation of GS.
- Published
- 2009
- Full Text
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41. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint.
- Author
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Melixetian M, Klein DK, Sørensen CS, and Helin K
- Subjects
- Amino Acid Sequence, Checkpoint Kinase 1, Enzyme Activation, G2 Phase genetics, HeLa Cells, Humans, Hydrophobic and Hydrophilic Interactions, Mitosis, Molecular Sequence Data, NIMA-Related Kinases, Phosphorylation, Protein Kinases chemistry, Protein Kinases genetics, RNA, Small Interfering metabolism, Radiation, Ionizing, Recombinant Proteins metabolism, Serine metabolism, Transfection, Ubiquitination, beta-Transducin Repeat-Containing Proteins genetics, beta-Transducin Repeat-Containing Proteins metabolism, cdc25 Phosphatases chemistry, cdc25 Phosphatases genetics, G2 Phase radiation effects, Protein Kinases metabolism, cdc25 Phosphatases metabolism
- Abstract
DNA damage-induced cell-cycle checkpoints have a critical role in maintaining genomic stability. A key target of the checkpoints is the CDC25A (cell division cycle 25 homologue A) phosphatase, which is essential for the activation of cyclin-dependent kinases and cell-cycle progression. To identify new genes involved in the G2/M checkpoint we performed a large-scale short hairpin RNA (shRNA) library screen. We show that NIMA (never in mitosis gene A)-related kinase 11 (NEK11) is required for DNA damage-induced G2/M arrest. Depletion of NEK11 prevents proteasome-dependent degradation of CDC25A, both in unperturbed and DNA-damaged cells. We show that NEK11 directly phosphorylates CDC25A on residues whose phosphorylation is required for beta-TrCP (beta-transducin repeat-containing protein)-mediated polyubiquitylation and degradation of CDC25A. Furthermore, we demonstrate that CHK1 (checkpoint kinase 1) directly activates NEK11 by phosphorylating it on Ser 273, indicating that CHK1 and NEK11 operate in a single pathway that controls proteolysis of CDC25A. Taken together, these results demonstrate that NEK11 is an important component of the pathway enforcing the G2/M checkpoint, suggesting that genetic mutations in NEK11 may contribute to the development of human cancer.
- Published
- 2009
- Full Text
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42. Time to embrace public health approaches to national and global challenges.
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Walker DK
- Subjects
- Child, Child Welfare, Female, Greenhouse Effect, Humans, Maternal Welfare, Military Medicine economics, Politics, United States, Universal Health Insurance, Health Care Reform, Health Priorities, Public Health Administration
- Published
- 2008
- Full Text
- View/download PDF
43. Lack of AMPKalpha2 enhances pyruvate dehydrogenase activity during exercise.
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Klein DK, Pilegaard H, Treebak JT, Jensen TE, Viollet B, Schjerling P, and Wojtaszewski JF
- Subjects
- AMP-Activated Protein Kinases, Amino Acid Sequence, Aminoimidazole Carboxamide analogs & derivatives, Aminoimidazole Carboxamide pharmacology, Animals, DNA, Mitochondrial genetics, DNA, Mitochondrial metabolism, Electron Transport Complex IV metabolism, Enzyme Activation, Enzyme Inhibitors pharmacology, In Vitro Techniques, Male, Mice, Mice, Knockout, Mitochondria, Muscle enzymology, Molecular Sequence Data, Multienzyme Complexes deficiency, Polymerase Chain Reaction, Protein Serine-Threonine Kinases deficiency, Ribonucleotides pharmacology, Multienzyme Complexes metabolism, Muscle, Skeletal enzymology, Physical Conditioning, Animal physiology, Protein Serine-Threonine Kinases metabolism, Pyruvate Dehydrogenase Complex metabolism
- Abstract
5'-AMP-activated protein kinase (AMPK) was recently suggested to regulate pyruvate dehydrogenase (PDH) activity and thus pyruvate entry into the mitochondrion. We aimed to provide evidence for a direct link between AMPK and PDH in resting and metabolically challenged (exercised) skeletal muscle. Compared with rest, treadmill running increased AMPKalpha1 activity in alpha(2)KO mice (90%, P < 0.01) and increased AMPKalpha2 activity in wild-type (WT) mice (110%, P < 0.05), leading to increased AMPKalpha Thr(172) (WT: 40%, alpha(2)KO: 100%, P < 0.01) and ACCbeta Ser(227) phosphorylation (WT: 70%, alpha(2)KO: 210%, P < 0.01). Compared with rest, exercise significantly induced PDH-E(1)alpha site 1 (WT: 20%, alpha(2)KO: 62%, P < 0.01) and site 2 (only alpha(2)KO: 83%, P < 0.01) dephosphorylation and PDH(a) [ approximately 200% in both genotypes (P < 0.01)]. Compared with WT, PDH dephosphorylation and activation was markedly enhanced in the alpha(2)KO mice both at rest and during exercise. The increased PDH(a) activity during exercise was associated with elevated glycolytic flux, and muscles from the alpha(2)KO mice displayed marked lactate accumulation and deranged energy homeostasis. Whereas mitochondrial DNA content was normal, the expression of several mitochondrial proteins was significantly decreased in muscle of alpha(2)KO mice. In isolated resting EDL muscles, activation of AMPK signaling by AICAR did not change PDH-E(1)alpha phosphorylation in either genotype. PDH is activated in mouse skeletal muscle in response to exercise and is independent of AMPKalpha2 expression. During exercise, alpha(2)KO muscles display deranged energy homeostasis despite enhanced glycolytic flux and PDH(a) activity. This may be linked to decreased mitochondrial oxidative capacity.
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- 2007
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44. AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
- Author
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Treebak JT, Glund S, Deshmukh A, Klein DK, Long YC, Jensen TE, Jørgensen SB, Viollet B, Andersson L, Neumann D, Wallimann T, Richter EA, Chibalin AV, Zierath JR, and Wojtaszewski JF
- Subjects
- Adenylate Kinase deficiency, Adenylate Kinase genetics, Aminoimidazole Carboxamide analogs & derivatives, Aminoimidazole Carboxamide pharmacology, Animals, Biological Transport, Catalysis, Glucose metabolism, Insulin pharmacology, Kinetics, Mice, Mice, Knockout, Phosphorylation, Protein Subunits metabolism, Ribonucleotides pharmacology, Adenylate Kinase metabolism, GTPase-Activating Proteins metabolism, Muscle, Skeletal enzymology
- Abstract
AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR). AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle. Recombinant AMPK heterotrimeric complexes (alpha1beta1gamma1 and alpha2beta2gamma1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.
- Published
- 2006
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45. Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle.
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Akerstrom TC, Birk JB, Klein DK, Erikstrup C, Plomgaard P, Pedersen BK, and Wojtaszewski J
- Subjects
- AMP-Activated Protein Kinases, Administration, Oral, Adult, Enzyme Activation drug effects, Glycogen metabolism, Humans, Male, Phosphorylation, Quadriceps Muscle metabolism, Time Factors, Exercise physiology, Glucose administration & dosage, Glucose pharmacology, Multienzyme Complexes metabolism, Muscle, Skeletal drug effects, Muscle, Skeletal enzymology, Protein Serine-Threonine Kinases metabolism
- Abstract
5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic master switch' regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK activation. We hypothesized that oral glucose ingestion during exercise would attenuate muscle AMPK activation. Nine male subjects performed two bouts of one-legged knee-extensor exercise at 60% of maximal workload. The subjects were randomly assigned to either consume a glucose containing drink or a placebo drink during the two trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P < 0.001), whereas glycerol (44.8 +/- 7.8 vs. 165.7 +/- 22.3 micromol L-1), and free fatty acid (169.3 +/- 9.5 vs. 1161 +/- 144.9 micromol L-1) concentrations were lower during the glucose compared to the placebo trial (both P < 0.001). Calculated fat oxidation was lower during the glucose trial (0.17 +/- 0.02 vs. 0.25 +/- 0.03 g min-1, P < 0.001). Activation of alpha2-AMPK was attenuated in the glucose trial compared to the placebo trial (0.24 +/- 0.07 vs. 0.46 +/- 0.14 pmol mg-1 min-1, P = 0.03), whereas the alpha1-AMPK activity was not different between trials or affected by exercise. AMPK and the downstream target of AMPK, acetyl-CoA carboxylase-beta, were phosphorylated as a response to exercise, but neither was significantly different between the two trials. We conclude that oral glucose ingestion attenuates the exercise-induced activation of alpha2-AMPK, bringing further support for a fuel-sensing role of AMPK in skeletal muscle.
- Published
- 2006
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46. Prevalence and correlates of depression as a secondary condition among adults with disabilities.
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Mitra M, Wilber N, Allen D, and Walker DK
- Subjects
- Activities of Daily Living, Adult, Demography, Depressive Disorder, Major psychology, Female, Health Behavior, Humans, Male, Prevalence, Social Support, Socioeconomic Factors, Depressive Disorder, Major epidemiology, Depressive Disorder, Major etiology, Disabled Persons psychology, Health Status, Surveys and Questionnaires
- Abstract
This article examines the associations among environmental factors, healthy behaviors, and depression in a sample of adults with major disabilities. When sociodemographics and type and level of disability were controlled, environmental factors (e.g., access to care, contacts with friends, and experience of assault) and risk behaviors (e.g., tobacco use, marijuana use, and physical exercise) were significant correlates of depression. Public health practice and research implications are discussed.
- Published
- 2005
- Full Text
- View/download PDF
47. Assessment partnerships between managed care and public health: the Massachusetts experience.
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Friedman DJ, Walker DK, Coltin KL, and Wood PA
- Subjects
- Cooperative Behavior, Humans, Massachusetts, Interinstitutional Relations, Managed Care Programs organization & administration, Needs Assessment, Public Health Administration
- Abstract
This article explores factors that facilitate or impede data sharing and linkage collaborations between state public health agencies and managed care organizations (MCOs). The exploration is based upon a review of both recent literature and the four years' experience of the Massachusetts Health Assessment Partnership (MHAP). MHAP has undertaken six collaborative data sharing and linkage projects that have involved diverse topics and methods. This article summarizes both exogenous and endogenous factors that have affected MHAP as a successful collaboration and indicates those factors that might be replicated in future collaborations between public health agencies and MCOs in other locations.
- Published
- 2002
- Full Text
- View/download PDF
48. Language proficiency and the enrollment of Medicaid-eligible children in publicly funded health insurance programs.
- Author
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Feinberg E, Swartz K, Zaslavsky AM, Gardner J, and Walker DK
- Subjects
- Child, Child Health Services statistics & numerical data, Health Care Surveys, Humans, Massachusetts, Multivariate Analysis, State Health Plans, United States, Universal Health Insurance, Aid to Families with Dependent Children statistics & numerical data, Child Health Services economics, Communication Barriers, Eligibility Determination, Ethnicity statistics & numerical data, Health Services Accessibility, Language, Medicaid statistics & numerical data
- Abstract
Objectives: The purpose of the study was to examine the effect of language proficiency on enrollment in a state-sponsored child health insurance program., Methods: 1055 parents of Medicaid-eligible children, who were enrolled in a state-sponsored child health insurance program, were surveyed about how they learned about the state program, how they enrolled their children in the program, and perceived barriers to Medicaid enrollment. We performed weighted chi2 tests to identify statistically significant differences in outcomes based on language. We conducted multivariate analyses to evaluate the independent effect of language controlling for demographic characteristics., Results: Almost a third of families did not speak English in the home. These families, referred to as limited English proficiency families, were significantly more likely than English-proficient families to learn of the program from medical providers, to receive assistance with enrollment, and to receive this assistance from staff at medical sites as compared to the toll-free telephone information line. They were also more likely to identify barriers to Medicaid enrollment related to "know-how"--that is, knowing about the Medicaid program, if their child was eligible, and how to enroll. Differences based on language proficiency persisted after controlling for marital status, family composition, place of residence, length of enrollment, and employment status for almost all study outcomes., Conclusions: This study demonstrates the significant impact of English language proficiency on enrollment of Medicaid-eligible children in publicly funded health insurance programs. Strong state-level leadership is needed to develop an approach to outreach and enrollment that specifically addresses the needs of those with less English proficiency.
- Published
- 2002
- Full Text
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49. Family income and the impact of a children's health insurance program on reported need for health services and unmet health need.
- Author
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Feinberg E, Swartz K, Zaslavsky A, Gardner J, and Walker DK
- Subjects
- Child, Child Health Services economics, Child Health Services supply & distribution, Health Services Accessibility statistics & numerical data, Humans, Insurance, Pharmaceutical Services statistics & numerical data, Massachusetts epidemiology, Medicaid statistics & numerical data, Child Health Services statistics & numerical data, Family Characteristics, Health Services Needs and Demand, Income statistics & numerical data, Insurance, Health statistics & numerical data, Medically Underserved Area
- Abstract
Objective: In an era when expanding publicly funded health insurance to children in higher income families has been the major strategy to increase access to health care for children, it is important to determine if the benefits to higher income children attributable to the receipt of health coverage are similar to those observed for lower income children. This study investigated how the likely impact of child health insurance expansions varies with family income., Methods: We surveyed parents or guardians of children who were enrolled in a state-sponsored health insurance program (Massachusetts Children's Medical Security Plan [CMSP]) that, before the implementation of the State Children's Health Insurance Plan (SCHIP), was open to all children regardless of income. A stratified sample of children was drawn from administrative files. We grouped children by income category (low-income [LI]: < or =133% of the federal poverty limit [FPL], middle-income [MI]: 134%-200% of the FPL, high-income [HI]: >200% of the FPL) that corresponded to eligibility for public health insurance programs in the state (Medicaid-eligible, SCHIP-eligible, and income that exceeded SCHIP eligibility). The majority of telephone interviews were conducted between November 1998 and March 1999. The overall response rate was 61.8%, yielding a sample of 996 children. The CSMP benefit package included comprehensive coverage for preventive and specialty care and limited coverage for ancillary services. Children enrolled in CMSP were not covered for inpatient hospital stays but those whose family income was <400% of the FPL were eligible to receive full or partial coverage for inpatient care through the state's free care pool. Although the CMSP benefit package did not meet the standards for a SCHIP, it is an approximate equivalent for children with incomes <200% of the FPL, who have full coverage for hospitalization through the state's free care pool. We used survey responses to develop 2 sets of indicators: the first for reported need for services and the second for unmet need or delays in care among children whose parents reported a need for the service. Within each set, we created indicators for 5 types of service (medical care, dental care, prescription drugs, vision services, and mental health care) and an additional composite indicator. The composite indicator aggregated all categories of services covered under CMSP in a single measure; it included all services except dental services, which, at the time of the study, were not covered by the program. The composite indicator served as the dependent variable in regression models. We used weighted chi2 tests to identify statistically significant differences in reported need and unmet need for the 5 types of medical services and the aggregate measure of all services covered by CMSP. We examined differences across income groups at 2 points in time: during the period children were uninsured before enrollment and while enrolled. We used weighted logistic regression to assess the independent association of family income with our dependent variables: reported need for health services and the presence of unmet need, controlling for other covariates. To evaluate the impact of participation in a child health insurance program, we examined unmet need before and after program enrollment, testing for statistical significance using McNemar's test for within-subject changes., Results: During the period of uninsurance before enrollment, prescription drugs (70%) was the health service needed most frequently, followed by medical (65%) and dental (57%) care. For the composite measure of services covered by CMSP, reported need for services was not significantly different by income. Need for medical care, dental care, and prescription drugs were significantly greater among children who had been uninsured for >6 months before enrollment. In addition, a significantly greater proportion of adolescent participants needed dental, vision, and mental health services than younger enrollees. While enrolled, among recently enrolled children, 77% need medical services, 68% prescription drugs, and 59% dental. In unadjusted models MI and HI children were more than 2 times as likely to report need for covered services as LI children. After adjusting for possible confounders, the effect of income was no longer significant. Instead, nonadolescents (odds ratio [OR]: 2.44; 95% confidence interval [CI]: 1.25-4.76) and children with white ethnicity (OR: 3.03; 95% CI: 1.43-6.67) were significantly more likely to report need for services. Before enrollment, unmet need among those who reported need for services was 5% for medical, 4% prescription drugs, 31% dental, 30% vision, and 33% mental health. For the composite measure of services covered by CMSP, LI children were significantly more likely to have had unmet need before enrollment than MI and HI children (20%, 10%, 7% by income). As compared with younger children, adolescents also had significantly greater unmet need for the composite measure (19% vs 10%). In multivariate models, not having a usual site of care was a highly significant predictor of unmet need or delayed care (OR: 3.41; 95% CI: 1.28-9.11). Ninety-eight percent of parents cited cost as the reason they had difficulty obtaining needed care. After enrollment, the proportion of children who needed care and had difficulty obtaining it decreased for all categories of care. Less than 1% of enrollees reported unmet need or delays in care for medical services and 3% for prescription drugs. Children who needed vision and mental health services continued to experience difficulty obtaining these services (17% for each category of care), although they were covered as part of the benefit package. Unmet need or delays in care for dental services, which at the time of the study were not covered under CMSP, remained high (27%). We found a significant reduction in unmet need among children in all income groups and no significant differences in unmet need by income. Controlling for other covariates, adolescents (OR: 3.11; 95% CI: 1.58-6.12) and children with compromised health (OR: 3.20; 95% CI: 1.35-7.58) were more likely to have had difficulty obtaining needed services while enrolled in the program. Children in larger families (OR: 0.40; 95% CI: 0.17-0.96) and who were previously uninsured for >6 months (OR: 0.45; 95% CI: 0.22-7.58) were less likely to have difficulty obtaining care., Conclusion: Our findings demonstrate the positive impact of providing health insurance coverage to children regardless of income. The HI children who enrolled in the program looked similar to children with incomes that meet current SCHIP eligibility guidelines, suggesting that expansions of SCHIPs to HI children should not qualitatively change the program dynamics.
- Published
- 2002
- Full Text
- View/download PDF
50. Applying the lessons learned in identifying children with special health care needs: next steps to assure quality care.
- Author
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Epstein SG and Walker DK
- Subjects
- Child, Child Health Services statistics & numerical data, Confidentiality, Culture, Humans, Mass Screening, United States, Child Health Services organization & administration, Chronic Disease, Disabled Children, Needs Assessment, Quality Assurance, Health Care organization & administration
- Published
- 2002
- Full Text
- View/download PDF
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