112 results
Search Results
2. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks
- Author
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Jon S. B. de Vlieger, Stefan Mühlebach, Gerrit Borchard, Elena Wolff-Holz, Sesha Neervannan, Daan J.A. Crommelin, Scott E. McNeil, Vinod P. Shah, Leonie Hussaarts, Beat Flühmann, Wenlei Jiang, Elwyn Griffiths, and Vera Weinstein
- Subjects
Drug ,business.industry ,General Neuroscience ,media_common.quotation_subject ,Biosimilar ,Pharmacology ,Public domain ,030226 pharmacology & pharmacy ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,White paper ,History and Philosophy of Science ,030220 oncology & carcinogenesis ,Agency (sociology) ,Medicine ,Regulatory science ,Engineering ethics ,business ,Equivalence (measure theory) ,Publication ,media_common - Abstract
Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified.
- Published
- 2017
3. Proliferation and Differentiation of Neuroglial Cells Isolated during Demyelination and Remyelination
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Monique Dubois-Dalcq, Kathryn V. Holmes, V. L. Friedrich, and Robert C. Armstrong
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medicine.anatomical_structure ,History and Philosophy of Science ,General Neuroscience ,medicine ,Remyelination ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Part VII. Poster Papers ,Neuroglial cells ,Cell biology - Published
- 2006
4. Regulation of the Acute Release of Tissue-type Plasminogen Activator from the Endothelium by Coagulation Activation Products
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J. J. Emeis and Gaubius Instituut TNO
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Plasmin ,medicine.medical_treatment ,plasminogen activator ,Pharmacology ,blood level ,Tissue plasminogen activator ,dose response ,fibrin ,conference paper ,chemistry.chemical_classification ,tissue plasminogen activator ,biology ,Chemistry ,General Neuroscience ,Blood Coagulation Factors ,enzyme activity ,medicine.anatomical_structure ,priority journal ,Coagulation ,Tissue Plasminogen Activator ,fibrinolysis ,prourokinase ,Human ,medicine.drug ,Adult ,endothelium ,Endothelium ,regulatory mechanism ,thrombogenesis ,blood clotting ,General Biochemistry, Genetics and Molecular Biology ,Fibrin ,History and Philosophy of Science ,protein secretion ,Fibrinolysis ,medicine ,Animals ,Humans ,blood clotting factor 12 ,plasma ,plasmin ,Animal ,fibrin formation ,enzyme ,Enzyme ,biology.protein ,Endothelium, Vascular ,fibrinolytic therapy ,Plasminogen activator ,blood clot lysis - Abstract
Chemicals/CAS: Blood Coagulation Factors; Tissue Plasminogen Activator, EC 3.4.21.68
- Published
- 1992
5. Methods and analyzers for hemoglobin measurement in clinical laboratories and field settings
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Carine Mapango, Ralph D. Whitehead, Maria Elena Jefferds, and Zuguo Mei
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Chromatography ,business.industry ,General Neuroscience ,Blood collection ,Venous blood ,030204 cardiovascular system & hematology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Hematology analyzer ,History and Philosophy of Science ,Medicine ,030212 general & internal medicine ,Hemoglobin measurement ,Hemoglobin ,business - Abstract
This paper describes and compares methods and analyzers used to measure hemoglobin (Hb) in clinical laboratories and field settings. We conducted a literature review for methods used to measure Hb in clinical laboratories and field settings. We described methods to measure Hb and factors influencing results. Automated hematology analyzer (AHA) was reference for all Hb comparisons using evaluation criteria of ±7% set by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). Capillary fingerprick blood usually produces higher Hb concentrations compared with venous blood. Individual drops produced lower concentrations than pooled capillary blood. Compared with the AHA: (1) overall cyanmethemoglobin (1.0-8.0 g/L), WHO Colour Scale (0.5-10.0 g/L), paper-based devices (5.0-7.0 g/L), HemoCue® Hb-201 (1.0-16.0 g/L) and Hb-301 (0.5-6.0 g/L), and Masimo Pronto® (0.3-14.0 g/L) overestimated concentrations; (2) Masimo Radical®-7 both under- and overestimated concentrations (0.3-104.0 g/L); and (3) other methods underestimated concentrations (2.0-16.0 g/L). Most mean concentration comparisons varied less than ±7% of the reference. Hb measurements are influenced by several analytical factors. With few exceptions, mean concentration bias was within ±7%, suggesting acceptable performance. Appropriate, high-quality methods in all settings are necessary to ensure the accuracy of Hb measurements.This paper describes and compares methods and analyzers used to measure hemoglobin (Hb) in clinical laboratories and field settings. With few exceptions, mean concentration bias was within ±7%, suggesting acceptable performance. Appropriate, high-quality methods in all settings are necessary to ensure the accuracy of Hb measurements.
- Published
- 2019
6. Use and interpretation of hemoglobin concentrations for assessing anemia status in individuals and populations: results from a WHO technical meeting
- Author
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Sant-Rayn Pasricha, María Nieves García-Casal, Juan Pablo Peña-Rosas, and Andrea J. Sharma
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medicine.medical_specialty ,Anemia ,clinical significance ,030204 cardiovascular system & hematology ,Global Health ,World Health Organization ,General Biochemistry, Genetics and Molecular Biology ,World health ,Article ,technical meeting ,03 medical and health sciences ,Hemoglobins ,0302 clinical medicine ,History and Philosophy of Science ,Clinical investigation ,Epidemiology ,medicine ,Humans ,Guideline development ,030212 general & internal medicine ,Economic potential ,business.industry ,General Neuroscience ,Interpretation (philosophy) ,Public health ,public health ,thresholds ,hemoglobin ,medicine.disease ,Family medicine ,business - Abstract
Anemia is an important public health problem that negatively affects health of individuals and economic potential of populations. An accurate case definition is critical for understanding burden and epidemiology of anemia, for planning public health interventions, and for clinical investigation and treatment of patients. The current threshold hemoglobin concentrations for diagnosis of anemia were proposed in 1968 and based on studies predominantly of Caucasian adult populations in Europe and North America. The World Health Organization is undertaking a project to review global guidelines for anemia. We describe the process of obtaining input from technical experts, researchers, blood bank experts, policy makers, and program implementers to identify key information or knowledge gaps for anemia diagnosis. From this scoping exercise, six priority areas were identified on diverse topics related to the use and interpretation of hemoglobin concentrations to diagnose anemia in individuals and populations. A call for authors was conducted to produce background, review, and research papers across priority topics. This paper summarizes the first technical meeting, which included commissioned papers as well as case studies, describes key data gaps identified, and describes the next steps in the guideline development process to assess available evidence and define knowledge gaps to improve anemia characterization.
- Published
- 2019
7. Strengthening implementation and utilization of nutrition interventions through research: a framework and research agenda
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Purnima Menon, Nabeeha M. Kazi, Erica Oakley, Sascha Lamstein, Susan Horton, Namukolo Covic, Paige Harrigan, Lynnette M. Neufeld, and David L. Pelletier
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medicine.medical_specialty ,Nutrition Interventions ,Public economics ,business.industry ,General Neuroscience ,Public health ,Environmental resource management ,Psychological intervention ,Developing country ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Child mortality ,Politics ,Malnutrition ,History and Philosophy of Science ,medicine ,Implementation research ,business - Abstract
Undernutrition among women and children contributes to almost half the global burden of child mortality in developing countries. The impact of nutrition on economic development has highlighted the need for evidence-based solutions and yielded substantial global momentum. However, it is now recognized that the impact of evidence-based interventions is limited by the lack of evidence on the best operational strategies for scaling up nutrition interventions. With the goal of encouraging greater engagement in implementation research in nutrition and generating evidence on implementation and utilization of nutrition interventions, this paper brings together a framework and a broad analysis of literature to frame and highlight the crucial importance of research on the delivery and utilization of nutrition interventions. The paper draws on the deliberations of a high-level working group, an e-consultation, a conference, and the published literature. It proposes a framework and areas of research that have been quite neglected, and yet are critical to better understanding through careful research to enable better translation of global and national political momentum for nutrition into public health impact.
- Published
- 2014
8. The clinical significance of drug craving
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Jennifer M. Wray and Stephen T. Tiffany
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Psychotherapist ,General Neuroscience ,digestive, oral, and skin physiology ,MEDLINE ,Outcome measures ,Craving ,behavioral disciplines and activities ,General Biochemistry, Genetics and Molecular Biology ,Treatment targets ,History and Philosophy of Science ,Intervention (counseling) ,mental disorders ,behavior and behavior mechanisms ,medicine ,Clinical significance ,Drug craving ,medicine.symptom ,Psychology ,Construct (philosophy) ,psychological phenomena and processes ,Clinical psychology - Abstract
Although drug craving has received considerable research attention over the past several decades, to date there has been no systematic review of the general clinical significance of craving. This paper presents an overview of measurement issues of particular relevance to a consideration of use of craving in clinical settings. The paper then considers the relevance of craving across a broad array of clinical domains, including diagnosis, prognostic utility, craving as an outcome measure, and the potential value of craving as a direct target of intervention. The paper is both descriptive and prescriptive, informed by the current state of the science on craving with recommendations for the definition of craving, assessment practices, future research, and clinical applications. We conclude that craving has considerable utility for diagnosis and as a clinical outcome, and that findings from future research will likely expand the clinical potential of the craving construct in the domains of prognosis and craving as a treatment target.
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- 2011
9. Race, socioeconomic status, and health: Complexities, ongoing challenges, and research opportunities
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David R. Williams, Jacinta P. Leavell, Chiquita Collins, and Selina A. Mohammed
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Gerontology ,medicine.medical_specialty ,business.industry ,General Neuroscience ,Public health ,Race and health ,Social class ,General Biochemistry, Genetics and Molecular Biology ,Health equity ,History and Philosophy of Science ,Environmental health ,Health care ,medicine ,Life course approach ,Social inequality ,business ,Psychology ,Socioeconomic status - Abstract
This paper provides an overview of racial variations in health and shows that differences in socioeconomic status (SES) across racial groups are a major contributor to racial disparities in health. However, race reflects multiple dimensions of social inequality and individual and household indicators of SES capture relevant but limited aspects of this phenomenon. Research is needed that will comprehensively characterize the critical pathogenic features of social environments and identify how they combine with each other to affect health over the life course. Migration history and status are also important predictors of health and research is needed that will enhance understanding of the complex ways in which race, SES, and immigrant status combine to affect health. Fully capturing the role of race in health also requires rigorous examination of the conditions under which medical care and genetic factors can contribute to racial and SES differences in health. The paper identifies research priorities in all of these areas.
- Published
- 2010
10. 'Grey Nomads' in Australia: Are They a Good Model for Successful Aging and Health?
- Author
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Paul Higgs and Frances Quirk
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Gerontology ,Aging ,Health Status ,media_common.quotation_subject ,Sense of community ,Health Promotion ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Promotion (rank) ,Quality of life (healthcare) ,History and Philosophy of Science ,Humans ,Medicine ,media_common.cataloged_instance ,European union ,Socioeconomics ,media_common ,Transients and Migrants ,Successful aging ,business.industry ,General Neuroscience ,Australia ,Social environment ,Health promotion ,Compression of morbidity ,business - Abstract
Lifestyle factors have been identified as being very important in determining health in later life. Nutrition, exercise, and social environment all interact to promote, or to limit, opportunities for an active and healthy post-working life. Not only are rates of chronic illness and disability reduced through the promotion of healthy lifestyles, but also quality of life is maintained through the compression of morbidity. Governments in Australia, as in the European Union and North America, have highlighted the importance of behavioral change in health promotion strategies with the aim of having an impact on the health-related lifestyles of their populations. This paper examines the example of a group of older Australians, the "grey nomads," who may present opportunities for examining health-related lifestyle changes. The term grey nomad refers to a portion of the older population in Australia who choose to use their later years and retirement as opportunities for travel and leisure, mainly within the confines of the Australian continent. As such, they are similar to groups in North America, such as the "snow birds," who travel to the southern United States to escape the colder winters of more northerly latitudes. Similar seasonal migrations occur from Northern to Southern Europe. What all share in common is an active culture/lifestyle of attempting to "age successfully." Grey nomads also participate in the creation of what can be termed postmodern communities, where they and other regular travelers may develop a sense of community feeling with others who are also regularly returning to the same spot year after year. Social support is highly predictive of health outcomes and such mobile communities may prove a positive factor in promoting good health. In this paper we examine whether the "grey nomads" represent a good model for improving health-related lifestyles in later life.
- Published
- 2007
11. Hemoglobin concentration and anemia diagnosis in venous and capillary blood: biological basis and policy implications
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Anura V Kurpad, Sheila Mburu, Lynnette M. Neufeld, Kenneth H. Brown, Reynaldo Martorell, and Leila M Larson
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Anemia ,General Neuroscience ,Population ,Gold standard (test) ,Venous blood ,030204 cardiovascular system & hematology ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Hematology analyzer ,History and Philosophy of Science ,medicine ,030212 general & internal medicine ,Hemoglobin ,Uttar pradesh ,Intensive care medicine ,education ,business ,Biological variability - Abstract
Anemia is an important public health challenge and accurate prevalence estimates are needed for program planning and tracking progress. While venous blood assessed by automated hematology analyzers is considered gold standard, most population-based surveys use point-of-care diagnostics and capillary blood to estimate population prevalence of anemia. Several factors influence hemoglobin (Hb) concentration, including human and analytic error, analysis method, and type of instrument, but it is unclear whether biological variability exists between venous and capillary blood. The objective of this paper was to systematically review sources of Hb variability and the potential biological basis for venous and capillary differences. We use data from a recent survey in the state of Uttar Pradesh, India, to illustrate the implications on anemia prevalence estimates. Significant differences in Hb concentration between capillary and venous blood samples are common. Most but not all find capillary Hb concentration to be higher than venous. Instrument/method variability and human error play an important role, but cannot fully explain these differences. A normative guide to data collection, analysis, and anemia diagnosis is needed to ensure consistent and appropriate interpretation. Further research is needed to fully understand the biological implications of venous and capillary Hb variability.
- Published
- 2019
12. Risk of excessive intake of vitamins and minerals delivered through public health interventions: objectives, results, conclusions of the meeting, and the way forward
- Author
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Lisa M Rogers, María Nieves García-Casal, Robin Mowson, and Ruben Grajeda
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0301 basic medicine ,medicine.medical_specialty ,030109 nutrition & dietetics ,business.industry ,General Neuroscience ,media_common.quotation_subject ,Public health ,Public health interventions ,Psychological intervention ,Legislature ,Micronutrient ,General Biochemistry, Genetics and Molecular Biology ,Unit (housing) ,03 medical and health sciences ,0302 clinical medicine ,History and Philosophy of Science ,Environmental health ,Medicine ,Quality (business) ,030212 general & internal medicine ,business ,Working group ,media_common - Abstract
The excessive consumption of certain vitamins and minerals could have deleterious consequences on health and development of individuals and populations. Simultaneous micronutrient-delivery interventions could be challenging in terms of safety as the target populations may overlap, posing a risk of excessive intake of certain micronutrients. The Evidence and Programme Guidance Unit of the Department of Nutrition for Health and Development of the World Health Organization convened a technical consultation on the risk of excessive intake of vitamins and minerals delivered through public health interventions in October 2017. The technical consultation's working groups identified important and emerging technical issues, lessons learned, and research priorities related to (1) planning, implementing, monitoring, and evaluating nutrition programs for the detection and control of the risk of excessive intakes; (2) safety, quality control, and assurance considerations; (3) coordination between public health nutrition interventions and other interventions and sectors; and (4) the legislative framework and policy coherence needed for simultaneous nutrition interventions. This paper provides the background and rationale of the technical consultation, synopsizes the presentations, and provides a summary of the main considerations proposed by the working groups.
- Published
- 2018
13. Inflammatory biomarkers of low back pain and disc degeneration: a review
- Author
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Ronald A. Lehman, Mitchell Levine, Lawrence G. Lenke, Hayley E. Jacobsen, Nadeen O. Chahine, Aysha N. Khan, Jansher Khan, K. Daniel Riew, and Christopher G. Filippi
- Subjects
0301 basic medicine ,Spinal stenosis ,Inflammation ,Intervertebral Disc Degeneration ,Disease ,Degeneration (medical) ,Bioinformatics ,Sensitivity and Specificity ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,History and Philosophy of Science ,Outcome Assessment, Health Care ,medicine ,Back pain ,Humans ,business.industry ,General Neuroscience ,Intervertebral disc ,medicine.disease ,Low back pain ,Natural history ,030104 developmental biology ,medicine.anatomical_structure ,Cytokines ,Inflammation Mediators ,medicine.symptom ,business ,Low Back Pain ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Biomarkers are biological characteristics that can be used to indicate health or disease. This paper reviews studies on biomarkers of low back pain (LBP) in human subjects. LBP is the leading cause of disability, caused by various spine-related disorders, including intervertebral disc degeneration, disc herniation, spinal stenosis, and facet arthritis. The focus of these studies is inflammatory mediators, because inflammation contributes to the pathogenesis of disc degeneration and associated pain mechanisms. Increasingly, studies suggest that the presence of inflammatory mediators can be measured systemically in the blood. These biomarkers may serve as novel tools for directing patient care. Currently, patient response to treatment is unpredictable with a significant rate of recurrence, and, while surgical treatments may provide anatomical correction and pain relief, they are invasive and costly. The review covers studies performed on populations with specific diagnoses and undefined origins of LBP. Since the natural history of LBP is progressive, the temporal nature of studies is categorized by duration of symptomology/disease. Related studies on changes in biomarkers with treatment are also reviewed. Ultimately, diagnostic biomarkers of LBP and spinal degeneration have the potential to shepherd an era of individualized spine medicine for personalized therapeutics in the treatment of LBP.
- Published
- 2017
14. A diagnosis and treatment gap for thiamine deficiency disorders in sub-Saharan Africa?
- Author
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Bola Adamolekun and Laurent Hiffler
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Sub saharan ,business.industry ,General Neuroscience ,food and beverages ,Biology ,Beriberi ,medicine.disease ,Protein supplementation ,General Biochemistry, Genetics and Molecular Biology ,Biotechnology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,History and Philosophy of Science ,chemistry ,Environmental health ,medicine ,Thiamine ,030212 general & internal medicine ,business ,human activities ,030217 neurology & neurosurgery ,Thiamine deficiency ,Subclinical infection - Abstract
Staple diets that are deficient in thiamine can result in low body thiamine levels, which may be subclinical or may manifest as a thiamine-deficiency syndrome. In many communities in the developing countries of Africa, the staple diets of polished rice or processed cassava are deficient in thiamine, and thus the communities are at high risk for marginal or frank thiamine deficiency unless their diets are supplemented by other sources of thiamine, such as protein meals and vegetables. African communities with large numbers of individuals in low socioeconomic strata are more likely to subsist on a monotonous diet of rice or cassava with minimal or no protein supplementation and are therefore particularly at risk of thiamine-deficiency disorders. Indeed, there is evidence of widespread biochemical thiamine deficiency from community-based studies in Africa. The protean manifestations of thiamine deficiency disorders in the developing countries of Africa are presented in this paper. We present evidence supporting the contention that there is a diagnosis and treatment gap for thiamine-deficiency disorders in Africa. We discuss research and clinical options for bridging the putative diagnosis and treatment gap for thiamine-deficiency disorders in the developing countries of Africa.
- Published
- 2017
15. Delivering an action agenda for nutrition interventions addressing adolescent girls and young women: priorities for implementation and research
- Author
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Mark A. Hanson, Angela Diaz, Rehana A Salam, Berthold Koletzko, Zulfiqar A Bhutta, Gilles Bergeron, Zohra S Lassi, Andrew M. Prentice, Robert E. Black, Luz Maria De-Regil, William J. Keenan, Mireille Mclean, Parul Christian, and Jonathan D. Klein
- Subjects
0301 basic medicine ,Gerontology ,Pediatrics ,medicine.medical_specialty ,Pregnancy ,030109 nutrition & dietetics ,Nutrition Interventions ,business.industry ,General Neuroscience ,Psychological intervention ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Preventive care ,03 medical and health sciences ,Malnutrition ,0302 clinical medicine ,Overnutrition ,History and Philosophy of Science ,Action (philosophy) ,Medicine ,030212 general & internal medicine ,business ,Evidence synthesis - Abstract
Adolescent nutritional behaviors are assuming considerable importance in nutrition interventions given their important relationships with medium- and long-term outcomes. This is the period when young people undergo major anatomical and physiological maturational changes in preparation for adulthood. Nutritional requirements during puberty are higher during adolescence than during the prepubertal stage and during adulthood. A significant proportion of adolescents also become parents, and hence the importance of their health and nutritional status before as well as during pregnancy has its impact on their own health, fetal well-being, and newborn health. In this paper, we describe the evidence-based nutrition recommendations and the current global guidance for nutrition actions for adolescents. Despite the limitations of available information, we believe that a range of interventions are feasible to address outcomes in this age group, although some would need to start earlier in childhood. We propose packages of preventive care and management comprising nutrition-specific and nutrition-sensitive interventions to address adolescent undernutrition, overnutrition, and micronutrient deficiencies. We discuss potential delivery platforms and strategies relevant to low- and middle-income countries. Beyond the evidence synthesis, there is a clear need to translate evidence into policy and for implementation of key recommendations and addressing knowledge gaps through prioritized research.
- Published
- 2017
16. Staple crops biofortified with increased vitamins and minerals: considerations for a public health strategy
- Author
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Dominique Van Der Straeten, Heber Gomez Malave, Mourad Moursi, Sandra Calkins, Maria Nieves Garcia Casal, Jessica Fanzo, Elise Talsma, Ismail Cakmak, Juan Pablo Peña-Rosas, Gerardo Zamora, Saurabh Mehta, and Céline Termote
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030109 nutrition & dietetics ,Equity (economics) ,business.industry ,General Neuroscience ,Public health ,Golden rice ,Biofortification ,food and beverages ,medicine.disease ,Micronutrient ,General Biochemistry, Genetics and Molecular Biology ,Agricultural economics ,Biotechnology ,03 medical and health sciences ,Malnutrition ,030104 developmental biology ,History and Philosophy of Science ,Agriculture ,medicine ,Business ,Working group - Abstract
Biofortification of staple crops has been proposed as a strategy to address micronutrient malnutrition, particularly with respect to insufficient intake of vitamin A, iron, zinc, and folate. The World Health Organization, in collaboration with the Food and Agriculture Organization of the United Nations and the Sackler Institute for Nutrition Science at the New York Academy of Sciences, convened a technical consultation entitled "Staple Crops Biofortified with Vitamins and Minerals: Considerations for a Public Health Strategy" in April 2016. Participants of the consultation reviewed the definition of biofortification of staple crops, patterns of crops production, processing, consumption, seed varieties, and micronutrient stability and bioavailability, as well as farmers' adoption and acceptability of the modified crops. Also discussed were economic, environmental, safety, and equity aspects of biofortified crops, as well as legal, policy, regulatory, and ethical issues for the implementation of biofortification strategies in agriculture and nutrition. Consultation working groups identified important and emerging technical issues, lessons learned, and research priorities to better support the evidence of improved nutrition and unintended adverse effects of biofortification. This paper provides the background and rationale of the technical consultation, synopsizes the presentations, and provides a summary of the main considerations proposed by the working groups.
- Published
- 2016
17. Correlating eligibility criteria generalizability and adverse events using Big Data for patients and clinical trials
- Author
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Chunhua Weng, Andrew Goldstein, Shreya Chakrabarti, Eileen Koski, Anando Sen, Shuang Wang, and Patrick B. Ryan
- Subjects
0301 basic medicine ,medicine.medical_specialty ,education.field_of_study ,GiST ,business.industry ,General Neuroscience ,Population ,Representativeness heuristic ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,History and Philosophy of Science ,Randomized controlled trial ,law ,Emergency medicine ,medicine ,Generalizability theory ,030212 general & internal medicine ,Metric (unit) ,Adverse effect ,business ,education - Abstract
Randomized controlled trials can benefit from proactive assessment of how well their participant selection strategies during the design of eligibility criteria can influence the study generalizability. In this paper, we present a quantitative metric called generalizability index for study traits 2.0 (GIST 2.0) to assess the a priori generalizability (based on population representativeness) of a clinical trial by accounting for the dependencies among multiple eligibility criteria. The metric was evaluated on 16 sepsis trials identified from ClinicalTrials.gov, with their adverse event reports extracted from the trial results sections. The correlation between GIST scores and adverse events was analyzed. We found that the GIST 2.0 score was significantly correlated with total adverse events and serious adverse events (weighted correlation coefficients of 0.825 and 0.709, respectively, with P < 0.01). This study exemplifies the promising use of Big Data in electronic health records and ClinicalTrials.gov for optimizing eligibility criteria design for clinical studies.
- Published
- 2016
18. Circadian rhythms and metabolism: from the brain to the gut and back again
- Author
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Fiona C Ritchey, Sridhar R. Vasudevan, Matthew R. Cribbet, Clara Bien Peek, Mathew D. Edwards, Erin Hanlon, Ellen Frank, Ryan W. Logan, and Jeremy J. Stubblefield
- Subjects
0301 basic medicine ,business.industry ,General Neuroscience ,Context (language use) ,medicine.disease ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,030104 developmental biology ,Pharmacological interventions ,History and Philosophy of Science ,Mood disorders ,Basic research ,medicine ,Bipolar disorder ,Circadian rhythm ,business ,Neuroscience ,Metabolic health - Abstract
This paper focuses on the relationship between the circadian system and glucose metabolism. Research across the translational spectrum confirms the importance of the circadian system for glucose metabolism and offers promising clues as to when and why these systems go awry. In particular, basic research has started to clarify the molecular and genetic mechanisms through which the circadian system regulates metabolism. The study of human behavior, especially in the context of psychiatric disorders, such as bipolar disorder and major depression, forces us to see how inextricably linked mental health and metabolic health are. We also emphasize the remarkable opportunities for advancing circadian science through big data and advanced analytics. Advances in circadian research have translated into environmental and pharmacological interventions with tremendous therapeutic potential.
- Published
- 2016
19. Estimating nutrient fortification levels in condiments and seasonings for public health programs: considerations and adaptations
- Author
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Sara E. Wuehler, Luz Maria De-Regil, Chowdhury S. B. Jalal, and Saskia J.M. Osendarp
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030109 nutrition & dietetics ,Small volume ,business.industry ,General Neuroscience ,Public health ,Fortification ,Target population ,General Biochemistry, Genetics and Molecular Biology ,Agricultural economics ,Biotechnology ,03 medical and health sciences ,Nutrient ,History and Philosophy of Science ,medicine ,business - Abstract
Condiments and seasonings have been considered as potential vehicles for fortification in place of, or in addition to, fortifiable staple foods. Methodologies for establishing fortification programs focus primarily on use of staple foods, which are consumed in larger portions than condiments and seasonings. Some fortification models assume self-limiting consumption relative to the maximum energy consumed by target populations. However, this assumption may prove incorrect for estimating fortification concentrations of condiments and seasonings because they may only provide negligible energy. Although flavor or color may limit consumption, these limits would vary across each condiment or seasoning vehicle. In addition, the small volume of condiments and seasonings consumed relative to staple foods can lead to proportionally larger potential errors than with staple foods when measuring usual dietary intakes for establishing safe and effective fortification concentrations. This paper reviews available methods for setting fortification levels, whether or how available methods or conceptual frameworks could be adapted to condiments and seasonings, and gaps in knowledge for appropriately using condiments and seasonings as vehicles for fortification in public health.
- Published
- 2016
20. Large-scale fortification of condiments and seasonings as a public health strategy: equity considerations for implementation
- Author
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Monica C Flores-Urrutia, Ana-Lucia Mayén, and Gerardo Zamora
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030109 nutrition & dietetics ,Equity (economics) ,business.industry ,General Neuroscience ,Intersectoral action ,Public health ,Environmental resource management ,Public sector ,Fortification ,Nutritional status ,General Biochemistry, Genetics and Molecular Biology ,Health equity ,03 medical and health sciences ,0302 clinical medicine ,History and Philosophy of Science ,medicine ,030212 general & internal medicine ,Implementation research ,Marketing ,business - Abstract
Fortification of staple foods with vitamins and minerals is an effective approach to increase micronutrient intake and improve nutritional status. The specific use of condiments and seasonings as vehicles in large-scale fortification programs is a relatively new public health strategy. This paper underscores equity considerations for the implementation of large-scale fortification of condiments and seasonings as a public health strategy by examining nonexhaustive examples of programmatic experiences and pilot projects in various settings. An overview of conceptual elements in implementation research and equity is presented, followed by an examination of equity considerations for five implementation strategies: (1) enhancing the capabilities of the public sector, (2) improving the performance of implementing agencies, (3) strengthening the capabilities and performance of frontline workers, (3) empowering communities and individuals, and (4) supporting multiple stakeholders engaged in improving health. Finally, specific considerations related to intersectoral action are considered. Large-scale fortification of condiments and seasonings cannot be a standalone strategy and needs to be implemented with concurrent and coordinated public health strategies, which should be informed by a health equity lens.
- Published
- 2016
21. Stage-directed individualized therapy in esophageal cancer
- Author
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Mark J. Krasna, Richard van Hillegersberg, Peter S.N. van Rossum, Khean-Lee Goh, Misha D. P. Luyer, Jelle P. Ruurda, Daniela Kandioler, and Lucas Goense
- Subjects
medicine.medical_specialty ,business.industry ,General Neuroscience ,General surgery ,medicine.medical_treatment ,Cancer ,Esophageal cancer ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Dissection ,0302 clinical medicine ,medicine.anatomical_structure ,History and Philosophy of Science ,Esophagectomy ,Neoadjuvant treatment ,030220 oncology & carcinogenesis ,Carcinoma ,Medicine ,030211 gastroenterology & hepatology ,Stage (cooking) ,business ,Lymph node - Abstract
Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.
- Published
- 2016
22. Urban climate versus global climate change-what makes the difference for dengue?
- Author
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Olivier Telle, Renaud Misslin, Alain Vaguet, Eric Daudé, and Richard Paul
- Subjects
030231 tropical medicine ,Climate change ,Aedes aegypti ,General Biochemistry, Genetics and Molecular Biology ,Dengue fever ,03 medical and health sciences ,0302 clinical medicine ,History and Philosophy of Science ,Urban climate ,Urbanization ,11. Sustainability ,medicine ,030212 general & internal medicine ,Urban heat island ,Socioeconomics ,biology ,Global temperature ,Ecology ,General Neuroscience ,Global warming ,15. Life on land ,biology.organism_classification ,medicine.disease ,3. Good health ,Geography ,13. Climate action - Abstract
The expansion in the geographical distribution of vector-borne diseases is a much emphasized consequence of climate change, as are the consequences of urbanization for diseases that are already endemic, which may be even more important for public health. In this paper, we focus on dengue, the most widespread urban vector-borne disease. Largely urban with a tropical/subtropical distribution and vectored by a domesticated mosquito, Aedes aegypti, dengue poses a serious public health threat. Temperature plays a determinant role in dengue epidemic potential, affecting crucial parts of the mosquito and viral life cycles. The urban predilection of the mosquito species will further exacerbate the impact of global temperature change because of the urban heat island effect. Even within a city, temperatures can vary by 10 °C according to urban land use, and diurnal temperature range (DTR) can be even greater. DTR has been shown to contribute significantly to dengue epidemic potential. Unraveling the importance of within-city temperature is as important for dengue as for the negative health consequences of high temperatures that have thus far been emphasized, for example, pollution and heat stroke. Urban and landscape planning designed to mitigate the non-infectious negative effects of temperature should additionally focus on dengue, which is currently spreading worldwide with no signs of respite.
- Published
- 2016
23. Disease models for the development of therapies for lysosomal storage diseases
- Author
-
Omid Motabar, Miao Xu, Juan J. Marugan, Marc Ferrer, Elizabeth A. Ottinger, and Wei Zheng
- Subjects
0301 basic medicine ,Drug ,education.field_of_study ,General Neuroscience ,media_common.quotation_subject ,Population ,Disease ,Biology ,Pharmacology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Probability of success ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,History and Philosophy of Science ,Lysosome ,Animal Disease Models ,medicine ,education ,Induced pluripotent stem cell ,030217 neurology & neurosurgery ,media_common - Abstract
Lysosomal storage diseases (LSDs) are a group of rare diseases in which the function of the lysosome is disrupted by the accumulation of macromolecules. The complexity underlying the pathogenesis of LSDs and the small, often pediatric, population of patients make the development of therapies for these diseases challenging. Current treatments are only available for a small subset of LSDs and have not been effective at treating neurological symptoms. Disease-relevant cellular and animal models with high clinical predictability are critical for the discovery and development of new treatments for LSDs. In this paper, we review how LSD patient primary cells and induced pluripotent stem cell-derived cellular models are providing novel assay systems in which phenotypes are more similar to those of the human LSD physiology. Furthermore, larger animal disease models are providing additional tools for evaluation of the efficacy of drug candidates. Early predictors of efficacy and better understanding of disease biology can significantly affect the translational process by focusing efforts on those therapies with the higher probability of success, thus decreasing overall time and cost spent in clinical development and increasing the overall positive outcomes in clinical trials.
- Published
- 2016
24. From IPEX syndrome toFOXP3mutation: a lesson on immune dysregulation
- Author
-
Maria Grazia Roncarolo, Federica Barzaghi, and Rosa Bacchetta
- Subjects
0301 basic medicine ,business.industry ,General Neuroscience ,FOXP3 ,Disease ,Immune dysregulation ,IPEX syndrome ,Autoimmune enteropathy ,medicine.disease_cause ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Autoimmunity ,03 medical and health sciences ,030104 developmental biology ,History and Philosophy of Science ,Immunology ,medicine ,Primary immunodeficiency ,Enteropathy ,business - Abstract
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder that increasingly has gained attention as a model of genetic autoimmunity. Numerous papers documenting the key clinical and molecular characteristics of IPEX have provided a detailed understanding of this devastating disease. IPEX is a primary immunodeficiency caused by mutations in the gene FOXP3, which encodes an essential transcription factor required for maintenance of thymus-derived regulatory T (tTreg) cells. tTreg cell dysfunction is the main pathogenic event leading to multiorgan autoimmunity in IPEX. In addition to the traditional clinical presentation (i.e., severe enteropathy, type 1 diabetes, and eczema), IPEX may encompass other variable and distinct clinical manifestations. As IPEX awareness and characterization have increased, so has identification of FOXP3 mutations, with at least 70 to date. Thus, while FOXP3 is the unifying gene, IPEX is a complex and diverse clinical continuum of disorders. Despite understanding IPEX pathogenesis, new treatment options have remained elusive, although early diagnosis led to hematopoietic stem cell transplantation (HSCT) and immunosuppression treatment and improved patient outcomes. Here, we review current knowledge about IPEX syndrome and highlight findings that could lead to novel targeted treatments.
- Published
- 2016
25. Reduced growth hormone signaling and methionine restriction: interventions that improve metabolic health and extend life span
- Author
-
Holly M. Brown-Borg
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Methionine ,General Neuroscience ,media_common.quotation_subject ,Stressor ,Psychological intervention ,Longevity ,Mitochondrion ,Biology ,Bioinformatics ,Growth hormone ,Affect (psychology) ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Endocrinology ,History and Philosophy of Science ,chemistry ,Internal medicine ,medicine ,Life expectancy ,media_common - Abstract
Interventions that improve health are often associated with longevity. Reduced growth hormone signaling has been shown to increase life span in mice by over 50%. Similarly, reductions in dietary intake of methionine, in rats and mice, result in life-span extension. Many factors affect metabolic health, mitochondrial function, and resistance to stressors, each of which influence aging and life span. This paper presents a comparison of these two interventions, as well as the results of a study combining these interventions, to understand potential mechanisms underlying their effectiveness in enhancing healthy aging.
- Published
- 2015
26. Risks of excess iodine intake in Ghana: current situation, challenges, and lessons for the future
- Author
-
Richmond Aryeetey, Wilna Oldewage-Theron, and Brenda Abu
- Subjects
0301 basic medicine ,Physiology ,Population ,Psychological intervention ,fortification ,Nutritional Status ,excess iodine intake ,Ghana ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,History and Philosophy of Science ,Risk Factors ,Environmental health ,medicine ,Humans ,030212 general & internal medicine ,Fortified Food ,Sodium Chloride, Dietary ,education ,Nutrition ,2. Zero hunger ,education.field_of_study ,030109 nutrition & dietetics ,business.industry ,General Neuroscience ,Health Policy ,Original Articles ,Awareness ,medicine.disease ,Iodine deficiency ,iodized salt ,3. Good health ,Iodised salt ,Food processing ,program implementation ,Dietary Iodine ,Food systems ,Original Article ,Public Health ,business ,Iodine - Abstract
In Ghana, iodine deficiency was first reported in 1994 among 33% of the population. A nationwide Universal Salt Iodization (USI) program plus other complementary interventions were subsequently implemented as a response. Our paper reviews the current risks of excess iodine status in Ghana and identifies policy and research gaps. A mixed methods review of 12 policies and institutional reports and 13 peer‐reviewed articles was complemented with consultations with 23 key informants (salt producers and distributors, food processors, regulatory agency officials, and healthcare providers) purposively sampled between May and August 2017. The findings show a strong policy environment indicated by regulations on food and salt fortification (Act 851), including the USI regulation. However, currently, only a third of Ghanaian households use adequately iodized salt. Recent evidence shows that voluntarily fortified processed foods (including condiments) supply a considerable amount of iodine to the food system. Limited biological impact data suggest possible household exposure to excessive dietary iodine (>15 parts per million). Currently, there is no systematic tracking of iodine content from fortified foods and other sources. Cross‐sectoral actions are needed to understand this situation better. Key research gap is the lack of comprehensive data on iodine content and intake from other sources in Ghana.
- Published
- 2018
27. TP53 is not a prognostic marker-clinical consequences of a generally disregarded fact
- Author
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Lindsay Brammen, Martina Mittlböck, Kausilia K. Krishnadath, Irene Kührer, Tamara Braunschmid, Wayne A. Phillips, Maria Westerhoff, Daniela Kandioler, Michael Gnant, Sonja Kappel-Latif, CCA - Imaging and biomarkers, Gastroenterology and Hepatology, and AGEM - Re-generation and cancer of the digestive system
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Treatment response ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Broad spectrum ,0302 clinical medicine ,History and Philosophy of Science ,Neoplasms ,medicine ,Biomarkers, Tumor ,Relevance (law) ,Humans ,Intensive care medicine ,Predictive marker ,business.industry ,General Neuroscience ,Prognosis ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,Clinical value ,Biomarker (medicine) ,Cancer development ,Tumor Suppressor Protein p53 ,business - Abstract
Technological progress within the last 15–20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and treatment response. As a consequence, a vast number of biomarkers have been proposed, but only a small fraction of them have found their way into clinical use. The aim of this paper is to describe the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. We name this procedure the “triple-R principle”: robustness, reproducibility, and relevance. The usefulness of this principle is illustrated with the marker TP53. Since it is mutated in a broad spectrum of cancer entities, TP53 can be considered a very promising marker. Thus, TP53 has been studied in detail but there is still no explicit consensus about its clinical value. By considering our own experience and reviewing the literature, we demonstrate that a major problem of current biomarker research is disregard of whether the biomarker is prognostic or predictive. As an example, it is demonstrated that TP53 is not a prognostic marker, but rather a purely predictive marker, and that disregard of this fact has made this otherwise strong biomarker appear as not being clinically useful so far.
- Published
- 2018
28. Natural and induced B-1 cell immunity to infections raises questions of nature versus nurture
- Author
-
Trang T. T. Nguyen, Elizabeth E. Waffarn, and Nicole Baumgarth
- Subjects
biology ,General Neuroscience ,Cell ,Spleen ,Inflammation ,General Biochemistry, Genetics and Molecular Biology ,B-1 cell ,Peritoneal cavity ,medicine.anatomical_structure ,History and Philosophy of Science ,Immunity ,Immunology ,medicine ,biology.protein ,Bone marrow ,Antibody ,medicine.symptom - Abstract
Mouse B-1 cells are not only major producers of steady-state natural antibodies but also rapid responders to infections and inflammation. These discrete functions may be the outcomes of distinct environmental or developmental triggers that drive B-1 cells toward IgM production or an effector cell fate. Alternatively, distinct B-1 cell subsets may exist, which differ in their functional plasticity. In this paper, we summarize existing data suggesting that B-1 cells form a heterogeneous group of cells with distinct developmental requirements and nonoverlapping functions. Most spleen B-1 cells differ in development from that of bone marrow and peritoneal cavity B-1 cells, in that they develop in the absence of natural IgM. Functional heterogeneity is revealed by findings that B-1 cells in the bone marrow and spleen, but not the peritoneal cavity, generate natural serum IgM, while the latter are rapid responders to inflammatory and infectious insults, resulting in their relocation to secondary lymphoid tissues. A clearer understanding of the developmental and functional differences within the B-1 cell pool may reveal how they might be harnessed for prophylaxis or therapy.
- Published
- 2015
29. Optimizing treatments for anxiety by age and genetics
- Author
-
Francis S. Lee and B. J. Casey
- Subjects
Genetics ,medicine.medical_specialty ,Human studies ,General Neuroscience ,Precision medicine ,General Biochemistry, Genetics and Molecular Biology ,Prevalence of mental disorders ,History and Philosophy of Science ,Neuroimaging ,medicine ,Anxiety ,medicine.symptom ,Psychology ,Psychiatry ,Clinical psychology - Abstract
This paper highlights recent human neuroimaging and cross-species developmental and genetic studies that examine how fear regulation varies by age and the individual, especially during the period of adolescence, when there is a peak in the prevalence of anxiety disorders. The findings have significant implications for understanding who may be at risk for anxiety disorders and for whom, and when, an exposure-based therapy may be most effective. We provide proof of concept for targeting treatment to the individual as a function of age and genetics, inferred from mouse and human studies, and suggest optimization of treatment for nonresponders.
- Published
- 2015
30. Short- and long-term rhythmic interventions: perspectives for language rehabilitation
- Author
-
Daniele Schön and Barbara Tillmann
- Subjects
Auditory perception ,Speech production ,Music therapy ,Speech perception ,General Neuroscience ,Dyslexia ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rhythm ,History and Philosophy of Science ,Phonological awareness ,Aphasia ,medicine ,medicine.symptom ,Psychology ,Cognitive psychology - Abstract
This paper brings together different perspectives on the investigation and understanding of temporal processing and temporal expectations. We aim to bridge different temporal deficit hypotheses in dyslexia, dysphasia, or deafness in a larger framework, taking into account multiple nested temporal scales. We present data testing the hypothesis that temporal attention can be influenced by external rhythmic auditory stimulation (i.e., musical rhythm) and benefits subsequent language processing, including syntax processing and speech production. We also present data testing the hypothesis that phonological awareness can be influenced by several months of musical training and, more particularly, rhythmic training, which in turn improves reading skills. Together, our data support the hypothesis of a causal role of rhythm-based processing for language processing and acquisition. These results open new avenues for music-based remediation of language and hearing impairment.
- Published
- 2015
31. Advances in stroke prevention
- Author
-
Mitchell S.V. Elkind and Ayesha Sherzai
- Subjects
Secondary prevention ,medicine.medical_specialty ,business.industry ,General Neuroscience ,medicine.medical_treatment ,Atrial fibrillation ,Revascularization ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Behavioral risk ,History and Philosophy of Science ,Stroke prevention ,Epidemiology ,Hyperlipidemia ,medicine ,Physical therapy ,cardiovascular diseases ,Intensive care medicine ,business ,Stroke - Abstract
Stroke remains to be a leading cause of disability. However, optimal strategies can prevent up to 80% of strokes. A large body of evidence supports many strategies for primary and secondary prevention of stroke. The purpose of this paper is to highlight recent major advances for management of modifiable medical and behavioral risk factors of stroke. Specific studies are highlighted, including those related to atrial fibrillation (AF), hypertension, revascularization, hyperlipidemia, antiplatelets, smoking, diet, and physical activity. Effective strategies include the use of novel oral anticoagulants for AF, antiplatelet therapy, and intensive lowering of atherosclerosis risk factors.
- Published
- 2015
32. Inflammatory and redox reactions in colorectal carcinogenesis
- Author
-
Giuseppe Poli, Fiorella Biasi, Tina Guina, Simone Calfapietra, and Mario Nano
- Subjects
Cell signaling ,Colorectal cancer ,business.industry ,General Neuroscience ,Inflammation ,Oxidative phosphorylation ,medicine.disease_cause ,medicine.disease ,Inflammatory bowel disease ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,Immunology ,Cancer cell ,medicine ,Cancer research ,medicine.symptom ,Carcinogenesis ,business ,Oxidative stress - Abstract
It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment.
- Published
- 2015
33. Neurophysiological models for new treatment development in schizophrenia: early sensory approaches
- Author
-
Daniel C. Javitt
- Subjects
medicine.diagnostic_test ,Working memory ,General Neuroscience ,Mismatch negativity ,Cognition ,Electroencephalography ,medicine.disease ,Neuropsychiatry ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,Event-related potential ,Schizophrenia ,medicine ,Psychology ,Neuroscience ,Neurocognitive - Abstract
Schizophrenia is a major mental disorder associated with core neurocognitive impairments. The ability to recreate these deficits in animal models is limited, hampering ongoing translational drug development efforts. This paper reviews the use of electroencephalography (EEG)-based neurophysiological measures, such as event-related potentials (ERPs) or event-related spectral perturbations (ERSPs), as novel translational biomarkers for both etiological and treatment development research in neuropsychiatry. In schizophrenia, cognitive impairments manifest as deficits not only in high-level processes, such as working memory or executive processing, but also as deficits in neurophysiological responses to simple auditory and visual stimuli. Moreover, neurophysiological responses can be assessed even in untrained animals and are therefore particularly amenable to translational, cross-species investigation. To date, several sensory-level ERP measures, including auditory mismatch negativity and N1, and visual P1 and steady-state responses, have been validated in both human clinical investigations and animal models. Deficits have been tied to impaired neurotransmission at N-methyl-d-aspartate-type glutamate receptors (NMDARs). Time-frequency analysis of ERSP permits further extension of these findings from physiological to circuit/cellular levels of analysis.
- Published
- 2015
34. Bipolar disorders in the Arab world: a critical review
- Author
-
Ziad Kronfol, Melvin G. McInnis, Pankaj Kumar, Elie Karam, Karsten Suhre, and Mostafa Zakaria Khalil
- Subjects
Western hemisphere ,education.field_of_study ,medicine.medical_specialty ,business.industry ,General Neuroscience ,Population ,Ethnic group ,Economic shortage ,Affect (psychology) ,Research findings ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Globalization ,History and Philosophy of Science ,Medicine ,Bipolar disorder ,education ,business ,Psychiatry - Abstract
Bipolar disorders are common psychiatric disorders that affect 1-5% of the population worldwide. Major advances in the epidemiology, pathophysiology, and treatment of the disorders have recently occurred. The majority of published reports, however, originate from the Western hemisphere, mostly Europe and the United States. There is a shortage of data from the Arab world on bipolar disorders. In an era of globalization and rapid communication, it is not clear to what extent research findings pertaining to one part of the world are by necessity applicable to other parts. Psychiatric disorders are known to be affected by the culture in which they occur, and knowledge of variations in illness presentation in different ethnic groups is also increasing. However, knowledge of variations affecting Arab populations remains quite limited. This paper provides a critical review of the literature on bipolar affective disorders in the Arab world, pointing to major gaps in knowledge and future opportunities to fill these gaps.
- Published
- 2015
35. Improving complementary feeding in Ghana: reaching the vulnerable through innovative business-the case of KOKO Plus
- Author
-
Kwaku Tano-Debrah, Devika Suri, Ricardo Uauy, Amonoo-Kuofi Hs, Firibu K. Saalia, Hitoshi Murakami, Yasuhiko Toride, Daniel Bruce Sarpong, Shibani Ghosh, Chie Furuta, Satoshi Kitamura, Nicholas Strutt, Kennedy Bomfeh, Grant J Aaron, Youzou Nakao, and Gloria E. Otoo
- Subjects
education.field_of_study ,Pediatrics ,medicine.medical_specialty ,Economic growth ,Social business ,business.industry ,General Neuroscience ,Population ,Developing country ,Social entrepreneurship ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Social marketing ,Product (business) ,Malnutrition ,History and Philosophy of Science ,General partnership ,Medicine ,business ,education - Abstract
Reaching vulnerable populations in low-resource settings with effective business solutions is critical, given the global nature of food and nutrition security. Over a third of deaths of children under 5 years of age are directly or indirectly caused by undernutrition. The Lancet series on malnutrition (2013) estimates that over 220,000 lives of children under 5 years of age can be saved through the implementation of an infant and young child feeding and care package. A unique project being undertaken in Ghana aims to bring in two elements of innovation in infant and young child feeding. The first involves a public-private partnership (PPP) to develop and test the efficacy and effectiveness of the delivery of a low-cost complementary food supplement in Ghana called KOKO Plus™. The second involves the testing of the concepts of social entrepreneurship and social business models in the distribution and delivery of the product. This paper shares information on the ongoing activities in the testing of concepts of PPPs, social business, social marketing, and demand creation using different delivery platforms to achieve optimal nutrition in Ghanaian infants and young children in the first 2 years of life. It also focuses on outlining the concept of using PPP and base-of-the-pyramid approaches toward achieving nutrition objectives.
- Published
- 2014
36. Influencing circadian and sleep-wake regulation for prevention and intervention in mood and anxiety disorders: what makes a good homeostat?
- Author
-
Bryony Sheaves, Elizabeth S. Maywood, Tina R. Goldstein, Jessica Thomas, Ellen Frank, Brandon S. Bentzley, Matt T. Bianchi, Marion Benabou, David Pritchett, and Genevieve Konopka
- Subjects
Homeostat ,General Neuroscience ,Sleep Wake Disorders ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Developmental psychology ,Mood ,History and Philosophy of Science ,Mood disorders ,medicine ,Anxiety ,medicine.symptom ,Set (psychology) ,Psychology ,Anxiety disorder ,Homeostasis - Abstract
All living organisms depend on homeostasis, the complex set of interacting metabolic chemical reactions for maintaining life and well-being. This is no less true for psychiatric well-being than for physical well-being. Indeed, a focus on homeostasis forces us to see how inextricably linked mental and physical well-being are. This paper focuses on these linkages. In particular, it addresses the ways in which understanding of disturbed homeostasis may aid in creating classes of patients with mood and anxiety disorders based on such phenotypes. At the cellular level, we may be able to compensate for the inability to study living brain tissue through the study of homeostatic mechanisms in fibroblasts, pluripotent human cells, and mitochondria and determine how homeostasis is disturbed at the level of these peripheral tissues through exogenous stress. We also emphasize the remarkable opportunities for enhancing knowledge in this area that are offered by advances in technology. The study of human behavior, especially when combined with our greatly improved capacity to study unique but isolated populations, offers particularly clear windows into the relationships among genetic, environmental, and behavioral contributions to homeostasis.
- Published
- 2014
37. Whole-of-society monitoring framework for sugar, salt, and fat consumption and noncommunicable diseases in India
- Author
-
Rakesh Pillai, Rajib Dasgupta, Narendra K. Arora, and Priyanka Rani Garg
- Subjects
Gerontology ,Consumption (economics) ,General Neuroscience ,Overweight ,medicine.disease ,Obesity ,General Biochemistry, Genetics and Molecular Biology ,Geography ,History and Philosophy of Science ,Diabetes mellitus ,Environmental health ,Urbanization ,medicine ,Per capita ,Human Development Index ,medicine.symptom ,Socioeconomic status - Abstract
India has experienced a rising prevalence of cardiometabolic risk factors in the past 15 years: the prevalence of diabetes has increased from 5.9% to 9.1%, hypertension from 17.2% to 29.2%, and obesity from 4% to 15%. The increase is among all socioeconomic groups and in urban and rural populations, though the quantum of change varies. A concomitant increase in per capita consumption of sugar from 22 to 55.3 g/day and total fat from 21.2 to 54 g/day was observed, with significant differences between states of high and low human development index (HDI). Per capita consumption of sugar, salt, and fat is consistently and significantly associated with overweight and obesity but variably associated with the occurrence of hypertension and diabetes. Market research shows that approximately 50–60% of total salt, sugar, and fat in Indian markets is procured by bulk purchasers, generally for manufacturing processed food items. This sector of the Indian economy is among the fastest growing, with several policy incentives. It is not clear from most of the data sets whether available information on per capita sugar, salt, and fat consumption has considered the contribution of processed and ready-to-eat food items. The unprecedented changes of rapid urbanization, mechanization, and globalization demand close monitoring of social, developmental, and economic determinants. This paper provides pieces of evidence to justify a whole-of-society (WoS) framework for monitoring the inputs, processes, and behavioral components of the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS) in India.
- Published
- 2014
38. Considerations for rice fortification in public health: conclusions of a technical consultation
- Author
-
Luz Maria De-Regil, Juan Pablo Peña-Rosas, Arnaud Laillou, and Regina Moench-Pfanner
- Subjects
Consumption (economics) ,Economic growth ,medicine.medical_specialty ,business.industry ,General Neuroscience ,Public health ,Fortification ,Psychological intervention ,food and beverages ,Staple food ,Micronutrient ,General Biochemistry, Genetics and Molecular Biology ,Biotechnology ,Intervention (law) ,History and Philosophy of Science ,medicine ,Mandate ,business - Abstract
Fortification of staple foods and commonly used condiments with vitamins and minerals has been considered one of the most cost-effective interventions to prevent and control micronutrient deficiencies. Because of its wide local consumption, acceptability, reach, and quantum of consumption, rice (Oryza sativa) far exceeds the requirements of a staple food vehicle that can be considered for fortification purposes at a population-level intervention. The World Health Organization (WHO) has the mandate to develop evidence-informed guidelines for the fortification of staple foods as a public health intervention, including rice fortification with micronutrients. The WHO, in collaboration with the Global Alliance for Improved Nutrition (GAIN), convened a consultation on “Technical Considerations for Rice Fortification in Public Health” in Geneva, Switzerland on October 9–10, 2012 to provide technical inputs to the guideline development process, particularly with reference to feasibility and implementability. The industrial and regulatory technical considerations in rice fortification, as well as the considerations for implementing it as a public health strategy and assuring equitable access and universal coverage, were reviewed in this consultation. This paper summarizes the discussions and priority research areas for the forthcoming years.
- Published
- 2014
39. Whole-of-society approach for public health policymaking: a case study of polycentric governance from Quebec, Canada
- Author
-
Nii A. Addy, Laurette Dubé, Alain Poirier, Nick Drager, and Chantal Blouin
- Subjects
medicine.medical_specialty ,Operationalization ,General Neuroscience ,Corporate governance ,media_common.quotation_subject ,Public health ,Context (language use) ,Public administration ,Policy analysis ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,State (polity) ,Work (electrical) ,Political science ,medicine ,Adaptive learning ,media_common - Abstract
In adopting a whole-of-society (WoS) approach that engages multiple stakeholders in public health policies across contexts, the authors propose that effective governance presents a challenge. The purpose of this paper is to highlight a case for how polycentric governance underlying the WoS approach is already functioning, while outlining an agenda to enable adaptive learning for improving such governance processes. Drawing upon a case study from Quebec, Canada, we employ empirically developed concepts from extensive, decades-long work of the 2009 Nobel laureate Elinor Ostrom in the governance of policy in nonhealth domains to analyze early efforts at polycentric governance in policies around overnutrition, highlighting interactions between international, domestic, state and nonstate actors and processes. Using information from primary and secondary sources, we analyze the emergence of the broader policy context of Quebec's public health system in the 20th century. We present a microsituational analysis of the WoS approach for Quebec's 21st century policies on healthy lifestyles, emphasizing the role of governance at the community level. We argue for rethinking prescriptive policy analysis of the 20th century, proposing an agenda for diagnostic policy analysis, which explicates the multiple sets of actors and interacting variables shaping polycentric governance for operationalizing the WoS approach to policymaking in specific contexts.
- Published
- 2014
40. Translational research investigations on ATP7A: an important human copper ATPase
- Author
-
Stephen G. Kaler
- Subjects
Genetics ,General Neuroscience ,ATP7A ,Occipital horn syndrome ,Biology ,medicine.disease ,Phenotype ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,Gene mapping ,medicine ,Menkes disease ,Menkes Kinky Hair Syndrome ,Copper deficiency ,Gene - Abstract
In more than 40 years since copper deficiency was delineated in pediatric subjects with Menkes disease, remarkable advances in our understanding of the clinical, biochemical, and molecular aspects of the human copper transporter ATP7A have emerged. Mutations in the gene encoding this multitasking molecule are now implicated in at least two other distinctive phenotypes: occipital horn syndrome and ATP7A-related isolated distal motor neuropathy. Several other novel inherited disorders of copper metabolism have been identified in the past several years, aided by advances in human gene mapping and automated DNA sequencing. In this paper, I review the history and evolution of our understanding of disorders caused by impaired ATP7A function, and outline future challenges.
- Published
- 2014
41. A model of social influence on body mass index
- Author
-
Joseph T. Ornstein and Ross A. Hammond
- Subjects
medicine.medical_specialty ,General Neuroscience ,Public health ,Behavioural sciences ,Body weight ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,medicine ,Leverage (statistics) ,Cluster analysis ,Psychology ,Body mass index ,Social psychology ,Health policy ,Social influence - Abstract
In this paper, we develop an agent-based model of social influence on body weight. The model's assumptions are grounded in theory and evidence from physiology, social psychology, and behavioral science, and its outcomes are tested against longitudinal data from American youth. We discuss the implementation of the model, the insights it generates, and its implications for public health policy. By explicating a well-grounded dynamic mechanism, our analysis helps clarify important dependencies for both efforts to leverage social influence for obesity intervention and efforts to interpret clustering of BMI in networks.
- Published
- 2014
42. Précis of nutrition of children and women in Haiti: analyses of data from 1995 to 2012
- Author
-
Jean Ernst Saint-Fleur, Rebecca J. Stoltzfus, Rebecca Heidkamp, Aissa Mamadoultaibou, Youssouf Koita, Jean Max Beauliere, Emmanuela Blain Durandisse, Bienfait Eca M'Mbakwa, Joseline Marhone Pierre, Mohamed Ag Ayoya, Ismael Ngnie-Teta, and Eddy Felix Daniel
- Subjects
Adult ,Adolescent ,Sanitation ,media_common.quotation_subject ,Population ,Psychological intervention ,Nutritional Status ,Developing country ,Child Nutrition Disorders ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,History and Philosophy of Science ,Environmental health ,Health care ,medicine ,Humans ,Longitudinal Studies ,Child ,education ,Empowerment ,media_common ,education.field_of_study ,business.industry ,General Neuroscience ,Malnutrition ,Nutrition Disorders ,Infant ,Maternal Nutritional Physiological Phenomena ,Middle Aged ,medicine.disease ,Haiti ,Child, Preschool ,Female ,Child Nutritional Physiological Phenomena ,business - Abstract
Between 1995 and 2012, many surveys including child and maternal nutrition indicators were conducted in Haiti. While many questions emerged from the results of those surveys, they have remained unanswered, in particular as they pertain to the determinants of poor children's and women's nutrition in Haiti. The purpose of this paper is to fill that gap and provide policymakers, program managers, and readers interested in nutrition issues in Haiti with information on (1) the trends and determinants of infant and young child feeding and food practices; (2) micronutrient deficiencies among children and women; (3) the status of severe acute malnutrition in children; (4) associations among women's empowerment, access to health care, water, and sanitation and child nutrition; (5) the current community-based early child care and nutrition initiatives; and (6) the status of nutrition governance in the country. By looking at many sources of data, including previously published and new data, we provide insight into major predictors of child malnutrition and associations among child feeding practices, maternal nutrition, and child growth outcomes. We also show that important progress has been made recently in the governance of nutrition programs and in child and maternal nutrition indicators, a result of effective evidence-based advocacy, partnerships, and design, implementation, and scale-up of nutrition-specific and sensitive interventions.
- Published
- 2014
43. Integrating early child development programs into health and nutrition services in Bangladesh: benefits and challenges
- Author
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Fahmida Tofail, Jena D. Hamadani, Syed N. Huda, and Baitun Nahar
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Rural Population ,Program evaluation ,Economic growth ,Urban Population ,Developing country ,General Biochemistry, Genetics and Molecular Biology ,Scientific evidence ,Child Development ,History and Philosophy of Science ,Early Medical Intervention ,Early Intervention, Educational ,Humans ,Medicine ,Early childhood ,Randomized Controlled Trials as Topic ,Government ,Child rearing ,Delivery of Health Care, Integrated ,business.industry ,General Neuroscience ,Environmental resource management ,Infant ,Child development ,Child, Preschool ,Child Nutritional Physiological Phenomena ,business ,Program Evaluation - Abstract
Bangladesh is one of the poorest countries of the world with the highest population density. The Bangladesh government recognizes the educational and financial benefits of early childhood development (ECD) and has incorporated ECD into the national plan of action. However, ECD activities are not fully established in the country and there have been few evaluations. In this paper, we present ECD programs that are integrated into health and nutrition services in Bangladesh. We present four evaluation reports of such programs and we also include seven published research projects showing evidence that such integrations are feasible. We provide short reviews on coverage, methodology, and effects of the published reports and share our experience of challenges faced and steps taken to solve them. Overall, very few programs are based on scientific evidence and fewer are even evaluated. The research projects so far conducted are promising and there is sufficient evidence on feasibility of integrating ECD activities into nutrition and health programs. Suggestions are made on measures to overcome the implementation problems and on suitable methods to establish high-quality ECD programs in Bangladesh and in other low- and middle-income countries.
- Published
- 2014
44. Issues in the timing of integrated early interventions: contributions from nutrition, neuroscience, and psychological research
- Author
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Michael K. Georgieff, Theodore D. Wachs, Sarah E. Cusick, and Bruce S. McEwen
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Population ,Psychological intervention ,Article ,General Biochemistry, Genetics and Molecular Biology ,Developmental psychology ,Child Development ,History and Philosophy of Science ,Stress, Physiological ,Early Medical Intervention ,Early Intervention, Educational ,Humans ,Medicine ,education ,education.field_of_study ,Delivery of Health Care, Integrated ,business.industry ,General Neuroscience ,Psychological research ,Stressor ,Age Factors ,Infant, Newborn ,Brain ,Infant ,Erikson's stages of psychosocial development ,Cognition ,Iron Deficiencies ,Child development ,Child, Preschool ,Child Nutritional Physiological Phenomena ,business ,Psychosocial ,Neuroscience ,Iron, Dietary ,Clinical psychology - Abstract
A central issue when designing multidimensional biological and psychosocial interventions for children who are exposed to multiple developmental risks is identification of the age period(s) in which such interventions will have the strongest and longest lasting effects (sensitive periods). In this paper, we review nutritional, neuroscientific, and psychological evidence on this issue. Nutritional evidence is used to identify nutrient-sensitive periods of age-linked dimensions of brain development, with specific reference to iron deficiency. Neuroscience evidence is used to assess the importance of timing of exposures to environmental stressors for maintaining neural, neuroendocrine, and immune systems integrity. Psychological evidence illustrates the sensitivity of cognitive and social-emotional development to contextual risk and protective influences encountered at different ages. Evidence reviewed documents that the early years of life are a sensitive period when biological or psychosocial interventions or exposure to risk or protective contextual influences can produce unique long-term influences upon human brain, neuroendocrine, and cognitive or psychosocial development. However, the evidence does not identify the early years as the sole sensitive time period within which to have a significant influence upon development. Choice of age(s) to initiate interventions should be based on what outcomes are targeted and what interventions are used.
- Published
- 2013
45. Circadian clocks, brain function, and development
- Author
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Katherine M. Sharkey, Liat Tikotzky, Ellen Frank, Chiara Cirelli, Nathaniel P. Hoyle, Michael McCarthy, Michelle M. Sidor, Brant P. Hasler, Lisa S. Talbot, and Karen L. Gamble
- Subjects
Mood Disorders ,General Neuroscience ,Period (gene) ,Circadian clock ,Brain ,medicine.disease ,Models, Biological ,Sleep in non-human animals ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,Mood disorders ,Circadian Clocks ,medicine ,Animals ,Humans ,Circadian rhythm ,Bipolar disorder ,Sleep ,Psychology ,Neuroscience ,Brain function ,Psychopathology - Abstract
Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic external environments. Components of the molecular clock are expressed throughout the brain and are centrally poised to play an important role in brain function. This paper focuses on key issues concerning the relationship among circadian clocks, brain function, and development, and discusses three topic areas: (1) sleep and its relationship to the circadian system; (2) systems development and psychopathology (spanning the prenatal period through late life); and (3) circadian factors and their application to neuropsychiatric disorders. We also explore circadian genetics and psychopathology and the selective pressures on the evolution of clocks. Last, a lively debate is presented on whether circadian factors are central to mood disorders. Emerging from research on circadian rhythms is a model of the interaction among genes, sleep, and the environment that converges on the circadian clock to influence susceptibility to developing psychopathology. This model may lend insight into effective treatments for mood disorders and inform development of new interventions.
- Published
- 2013
46. Formative research methods for designing culturally appropriate, integrated child nutrition and development interventions: an overview
- Author
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Margaret E. Bentley, Hilary Creed-Kanashiro, Heather Wasser, Susan L. Johnson, Melissa Cunningham, Sylvia Fernandez Rao, and Monal R. Shroff
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Psychological intervention ,India ,Health Promotion ,Article ,General Biochemistry, Genetics and Molecular Biology ,Developmental psychology ,Formative assessment ,Child Development ,History and Philosophy of Science ,Early Medical Intervention ,Early Intervention, Educational ,Cognitive development ,Humans ,Medicine ,Early childhood ,Maternal Behavior ,Medical education ,Cultural Characteristics ,Delivery of Health Care, Integrated ,business.industry ,General Neuroscience ,Infant, Newborn ,Infant ,Child development ,Health promotion ,Caregivers ,Child, Preschool ,Female ,Program Design Language ,Child Nutritional Physiological Phenomena ,business ,Psychosocial - Abstract
Nutritional and developmental insults in the first few years of life have profound public health implications, including substantial contributions to neonatal, infant, and early childhood morbidity and mortality, as well as longer term impacts on cognitive development, school achievement, and worker productivity. Optimal development that can lead to the attainment of the individual's fullest potential therefore requires a combination of genetic capacity, adequate nutrition, psychosocial stimulation, and safe, clean physical environments. Researchers and policymakers have called for integrated child nutrition and development interventions for more than twenty years, yet there are only a handful of efficacy trials and even fewer examples of integrated interventions that have been taken to scale. While a critical component to the design of such interventions is formative research, there is a dearth of information in both the literature and policy arenas to guide this phase of the process. To move the field forward, this paper first provides an overview of formative research methods with a focus on qualitative inquiry, a description of the critical domains to be assessed (infant and young child feeding, responsive feeding, and child development), and currently available resources. Application of these methods is provided through a real-world case study—the design of an integrated nutrition and child development efficacy trial in Andhra Pradesh, India. Recommendations for next steps are discussed, the most important of which is the need for a comprehensive set of formative guidelines for designing locally tailored, culturally appropriate integrated interventions.
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- 2013
47. Risk for anxiety and implications for treatment: developmental, environmental, and genetic factors governing fear regulation
- Author
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B. J. Casey and Catherine A. Hartley
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medicine.medical_specialty ,General Neuroscience ,medicine.medical_treatment ,Human factors and ergonomics ,Poison control ,Suicide prevention ,General Biochemistry, Genetics and Molecular Biology ,Cognitive behavioral therapy ,History and Philosophy of Science ,Injury prevention ,Cognitive therapy ,medicine ,Anxiety ,medicine.symptom ,Psychiatry ,Psychology ,Behavioural genetics ,Clinical psychology - Abstract
Anxiety disorders are the most common of the psychiatric disorders affecting as many as 10% of youth, with a peak during adolescence. A core component of these disorders is an unremitting fear in the absence of present threat. One of the most commonly used therapies to treat these disorders is exposure-based cognitive behavioral therapy that identifies the source of the fear and anxiety and then desensitizes the individual to it. This treatment builds on basic principles of fear extinction learning. A number of patients improve with this therapy, but 40–50% do not. This paper provides an overview of recent empirical studies employing both human imaging and cross-species behavioral genetics to examine how fear regulation varies across individuals and across development, especially during adolescence. These studies have important implications for understanding who may be at risk for anxiety disorders and for whom and when during development exposure-based therapies may be most effective.
- Published
- 2013
48. The esophageal mucosa and submucosa: immunohistology in GERD and Barrett's esophagus
- Author
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Helmut Neumann, Michael Vieth, Susan C. Abraham, Hala El-Zimaity, Catherine J. Streutker, Andrew M. Bellizzi, Melissa P. Upton, Henry D. Appelman, Markus F. Neurath, Helen H. Wang, and Xavier Sagaert
- Subjects
Lamina propria ,medicine.medical_specialty ,Muscularis mucosae ,business.industry ,General Neuroscience ,medicine.disease ,Gastroenterology ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,medicine.anatomical_structure ,History and Philosophy of Science ,Internal medicine ,Barrett's esophagus ,Submucosa ,medicine ,GERD ,Adenocarcinoma ,Esophagus ,business ,CDX2 - Abstract
This paper presents commentaries on the microscopic morphology of esophageal squamous epithelium; the frequency of duplication of the muscularis mucosae (MM) in Barrett's esophagus (BE); the significance of multilayered epithelium; whether cells in the lamina propria reflect those in the epithelium; how stem cells are identified in the squamous esophagus; dilated intercellular spaces; the metastasizing potential of early carcinoma-dependent, molecular or immunohistochemical tests that improve diagnosis; the role of immunohistochemistry IHC in grading of neoplasia in Barrett's esophagus and defining the risk of progression to adenocarcinoma; the roles of CDX1 and CDX2 in squamous and cardiac mucosa; and the role of desmosomal cadherins and lectins in squamous and cardiac mucosa.
- Published
- 2013
49. Translational issues in targeting brown adipose tissue thermogenesis for human obesity management
- Author
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Abdul G. Dulloo
- Subjects
0303 health sciences ,medicine.medical_specialty ,General Neuroscience ,030209 endocrinology & metabolism ,Biology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Anti-Obesity Agents ,medicine.anatomical_structure ,Endocrinology ,History and Philosophy of Science ,Energy expenditure ,Weight loss ,Internal medicine ,Brown adipose tissue ,medicine ,Obesity management ,medicine.symptom ,Thermogenesis ,030304 developmental biology ,Human obesity ,Target weight - Abstract
The recent advancements in unraveling novel mechanisms that control the induction, (trans)differentiation, proliferation, and thermogenic activity and capacity of brown adipose tissue (BAT), together with the application of imaging techniques for human BAT visualization, have generated optimism that these advances will provide novel strategies for targeting BAT thermogenesis, leading to efficacious and safe obesity therapies. This paper first provides an overview of landmark events of the past few decades that have been driving the search for pharmaceutical and nutraceutical compounds that would increase BAT thermogenesis for obesity management. It then addresses issues about what could be expected from an ideal thermogenic antiobesity approach, in particular to what extent daily energy expenditure will need to increase in order to achieve long-term weight loss currently achievable only through bariatric surgery, and whether the human body will have enough thermogenic capacity to reach this target weight loss by future therapies focused on BAT.
- Published
- 2013
50. Outcomes of esophageal surgery, especially of the lower esophageal sphincter
- Author
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Luigi Bonavina, Attila Csendes, Greta Saino, Demetrio Cavadas, Stefano Siboni, Edgar Figueredo, Owen Korn, Eelco B. Wassenaar, Italo Braghetto, and Lee L. Swanstrom
- Subjects
medicine.medical_specialty ,Paraesophageal ,business.industry ,General Neuroscience ,General surgery ,Reflux ,medicine.disease ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,Antireflux operation ,Surgery ,History and Philosophy of Science ,otorhinolaryngologic diseases ,Esophageal sphincter ,medicine ,GERD ,Esophageal surgery ,Hernia ,business ,Esophagitis - Abstract
This paper includes commentaries on outcomes of esophageal surgery, including the mechanisms by which fundoduplication improves lower esophageal sphincter (LES) pressure; the efficacy of the Linx™ management system in improving LES function; the utility of radiologic characterization of antireflux valves following surgery; the correlation between endoscopic findings and reported symptoms following antireflux surgery; the links between laparoscopic sleeve gastrectomy and decreased LES pressure, endoscopic esophagitis, and gastroesophageal reflux disease (GERD); the less favorable outcomes following fundoduplication among obese patients; the application of bioprosthetic meshes to reinforce hiatal repair and decrease the incidence of paraesophageal hernia; the efficacy of endoluminal antireflux procedures, and the limited efficacy of revisional antireflux operations, underscoring the importance of good primary surgery and diligent work-up to prevent the necessity of revisional procedures.
- Published
- 2013
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