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The inception and development of basic animal health systems: examples of German development co-operation.

About thirty years ago the financial, logistic and manpower resources of veterinary and animal production services in the developing world were stretched to the limit. Epizootic disease control was their main and often only field activity, which left livestock owners to manage their daily production and health problems alone. To meet their requirements, Veterinary Services in these countries came under increasing public and political pressure to modify and adjust their approaches. This gave rise to a series of workshops in Africa (e.g. Bujumbura in Burundi and Blantyre in Malawi) and South-East Asia (e.g. Singapore, and Khon Kaen in Thailand), most of which were organised and facilitated by the German Agency for Technical Co-operation (GTZ) in close collaboration with French and British development co-operation agencies and universities. These workshops stimulated discussion with the key stakeholders and, thus, were most beneficial in supporting the process of developing alternative approaches. This paper reports in particular on the outcomes of the regional workshops held in Bujumbura, Burundi, in 1984, Blantyre, Malawi, in 1985, Bangui, Central African Republic, in 1988, Khon Kaen, Thailand, in 1989, Schmitten, Germany, in 1991, and Mzuzu, Malawi, in 1996 and 2000. For more than two decades, concepts of community-based livestock services in general, and primary animal health activities (PAHAs) in particular, have been developed and established in various developing countries. Over the years the PAHA concept has proved to be effective and has shown that livestock-keeping communities clearly benefit from such programmes. In presenting key features from some prominent and successful project examples (GTZ-supported projects in Thailand, Malawi and Somalia) it can be demonstrated that such approaches are not static but rather dynamic, requiring open minded innovative partners on both sides. Over the last few years, the delivery of PAHA has become the domain of non-governmental organisations. The propagation and application of this approach in various developing countries with limited veterinary infrastructure is supporting a privatisation process within the existing governmental veterinary structures, thus, allowing veterinary departments more freedom to focus on their core functions.

Animal Husbandry↗

Animal welfare and developing countries: opportunities for trade in high-welfare products from developing countries.

Discussion on the potential for developing countries to develop trade in niche markets such as higher welfare standards has been highlighted with moves by the World Organisation for Animal Health (OIE) to set internationally agreed standards for animal welfare. This paper examines the existing and potential trade in value-added higher welfare products using case studies in the beef and poultry sectors from three countries in Africa, Asia and Latin America. It shows that at present there is only a small trade in these products but that this can have a major effect at a national level. In the beef export trade from Namibia, the existence of the only assurance scheme in Africa setting standards in hygiene, veterinary care and animal welfare has created a trusted, safe and healthy product and ensured that Namibia has grown into Africa's largest exporter of beef to the European Union. In Thailand, the broiler industry, which has enjoyed annual growth in the past 15 years, is developing value-added products to develop markets to counter competition from other countries. The development and implementation of standards for organic products in both Thailand and Argentina over the past decade have also resulted in growth in the export markets of these products. The paper concludes that there is growth potential for the sectors in all three markets which can be assisted by the development of OIE baseline standards.

Animal Welfare↗

Transfer of regulatory toxicology from developed to developing countries.

Over the past two decades, industrialized nations have addressed and attempted to solve the problems of chemical risk through the development of laws, government and private organizations, and specialized manpower. Developing nations are now recognizing that the presence of toxicants in the environment, foods, consumer products, and the workplace can seriously affect human health, the ecology, international relations, and economic activities such as trade and tourism. The design and implementation of regulatory programs in developing countries is hampered by lack of government and public concern, pressure of more urgent needs, vested interests of industry, and lack of adequately trained professionals. These factors have allowed developed nations to sell abroad drugs, pesticides, and other chemicals considered too hazardous for use in their own countries. Conversely, products from developing nations must comply with rigorous standards for acceptance by developed nations. Some of these problems would be lessened by agreement on international chemical control guidelines. Multilateral availability of complete information about chemicals is essential. The coordination of this effort should be in the hands of international organizations and reinforced by bilateral agreements between countries. Appropriate public education and economic incentives at the national level would help in enforcing regulatory toxicology.

Developing Countries↗

The relative contribution of prematurity and fetal growth retardation to low birth weight in developing and developed societies.

The relative proportions of prematurity (less than or equal to 2,500 gm less than 37 weeks' gestation) and intrauterine growth retardation-low birth weight (IUGR-LBW) (less than or equal to 2,500 gm, greater than or equal 37 weeks' gestation) among total LBW infants were studied in 11 regions in the developed world and 25 developing areas where known gestational ages and birth weights were reported. In developing countries a straight correlation was observed between total LBW incidence and IUGR-LBW incidence rates (r = 0.95; b = 0.98; p less than 0.001); in contrast, prematurity was not significantly associated with total LBW incidence. Data from the developed population showed results exactly opposite to those described for developing areas. Therefore, when the incidence of LBW is higher than 10%, it is almost exclusively due to the increase in IUGR-LBW infants, while prematurity remains almost unchanged (5% to 7%). When LBW incidence is less than 10% (mean=6%), preterm infants represent the major component of LBW. Environmental factors susceptible to changing socioeconomic conditions may be responsible for the observed differences.

Birth Weight↗

Child development: risk factors for adverse outcomes in developing countries.

Poverty and associated health, nutrition, and social factors prevent at least 200 million children in developing countries from attaining their developmental potential. We review the evidence linking compromised development with modifiable biological and psychosocial risks encountered by children from birth to 5 years of age. We identify four key risk factors where the need for intervention is urgent: stunting, inadequate cognitive stimulation, iodine deficiency, and iron deficiency anaemia. The evidence is also sufficient to warrant interventions for malaria, intrauterine growth restriction, maternal depression, exposure to violence, and exposure to heavy metals. We discuss the research needed to clarify the effect of other potential risk factors on child development. The prevalence of the risk factors and their effect on development and human potential are substantial. Furthermore, risks often occur together or cumulatively, with concomitant increased adverse effects on the development of the world's poorest children.

Child Development↗

Developmental care for promoting development and preventing morbidity in preterm infants.

BACKGROUND: Preterm infants experience a range of morbidity related to the immaturity of their organ systems and to concurrent disease states. An unfavourable environment in the neonatal intensive care unit (NICU) may compound this morbidity. Modification of the environment could minimize the iatrogenic effects. Developmental care is a broad category of interventions designed to minimize the stress of the NICU environment. These interventions may include one or more elements such as control of external stimuli (vestibular, auditory, visual, tactile), clustering of nursery care activities, and positioning or swaddling of the preterm infant. Individual strategies have also been combined to form programs, such as the 'Neonatal Individualized Developmental Care and Assessment Program' (NIDCAP) (Als 1986). OBJECTIVES: In preterm infants, do developmental care interventions reduce neurodevelopmental delay, poor weight gain, length of hospital stay, length of mechanical ventilation, physiological stress and other clinically relevant adverse outcomes? SEARCH STRATEGY: The Neonatal Review Group search strategy was utilized. Searches were made of Medline from 1966 to July, 2000, and of CINAHL, The Cochrane Library, and conference and symposia proceedings in the English language from 1990 to July, 2000. A list of all relevant articles was sent to two experts in the field to identify any omissions or additional unpublished studies. SELECTION CRITERIA: Randomized trials in which elements of developmental care are compared to routine nursery care for infants < 37 weeks gestation and that measured clinically relevant outcomes. Reports were in English or a language for which a translator was available. Computerized searches were conducted and all potentially relevant titles and abstracts were extracted. Retrieved articles were assessed for relevance independently by two reviewers, based on predetermined criteria. Articles that met all criteria for relevance were assessed for methodological quality based on predetermined criteria. Articles judged to have the appropriate quality by both reviewers were included in the analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors. Meta-analyses were conducted for each intervention where the same outcome measures and/or instruments were used within comparable time points. MAIN RESULTS: This review detected 31 eligible randomized controlled trials involving four major groups of developmental care interventions, 19 sub-groups and multiple clinical outcomes. The results of the review indicate that developmental care interventions demonstrate some benefit to preterm infants with respect to: improved short-term growth outcomes, decreased respiratory support, decreased length and cost of hospital stay, and improved neurodevelopmental outcomes to 24 months corrected age. These findings were based on two or three small trials for each outcome, and did not involve meta-analyses of more than two trials for any one outcome. Although a number of other benefits were demonstrated, those results were from single studies with small sample sizes. The lack of blinding of the assessors was a significant methodological flaw in half of the studies. The cost of the interventions and personnel was not considered in any of the studies. REVIEWER'S CONCLUSIONS: Because of the inclusion of multiple interventions in most studies, the determination of the effect of any single intervention is difficult. Although there is evidence of some benefit of developmental care interventions overall, and no major harmful effects reported, there were a large number of outcomes for which no or conflicting effects were demonstrated. The single trials that did show a significant effect of an intervention on a major clinical outcome were based on small sample sizes, and the findings were often not supported in other small trials. Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.

Developmental Disabilities↗

Initial retinoid requirement for early avian development coincides with retinoid receptor coexpression in the precardiac fields and induction of normal cardiovascular development.

Vitamin A requirement for early embryonic development is clearly evident in the gross cardiovascular and central nervous system abnormalities and an early death of the vitamin A-deficient quail embryo. This retinoid knockout model system was used to examine the biological activity of various natural retinoids in early cardiovascular development. We demonstrate that all-trans-, 9-cis-, 4-oxo-, and didehydroretinoic acids, and didehydroretinol and all-trans-retinol induce and maintain normal cardiovascular development as well as induce expression of the retinoic acid receptor beta2 in the vitamin A-deficient quail embryo. The expression of RARbeta2 is at the same level and at the same sites where it is expressed in the normal embryo. Retinoids provided to the vitamin A-deficient embryo up to the 5-somite stage of development, but not later, completely rescue embryonic development, suggesting the 5-somite stage as a critical retinoid-sensitive time point during early avian embryogenesis. Retinoid receptors RARalpha, RARgamma, and RXRalpha are expressed in both the precardiac endoderm and mesoderm in the normal and the vitamin A-deficient quail embryo, while the expression of RXRgamma is restricted to precardiac endoderm. Vitamin A deficiency downregulates the expression of RARalpha and RARbeta. Our studies provide strong evidence for a narrow retinoid-requiring developmental window during early embryogenesis, in which the presence of bioactive retinoids and their receptors is essential for a subsequent normal embryonic development.

Animals↗

A development-specific histone H3 localizes to the developing macronucleus of Euplotes.

During the process of macronuclear development, the ciliate Euplotes crassus undergoes extensive programmed DNA rearrangement. Previous studies have identified a gene, H3(P), that is expressed only during sexual reproduction and is predicted to encode a variant histone H3 protein. In the current study, an antiserum to the H3(P) protein has been generated. The antiserum has been used to demonstrate that H3(P) is maximally expressed during the polytene chromosome stage of macronuclear development. Moreover, H3(P) is localized to the developing macronucleus, but not other nuclei present within the cell. Additional studies indicate that at least one additional variant histone is also present within the developing macronucleus. The results indicate that there are significant changes in nucleosome composition within the developing macronucleus, and provide additional support for the notion that changes in chromatin structure play a role in the DNA rearrangement processes of macronuclear development. genesis 26:179-188, 2000.

Amino Acid Sequence↗

Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. III. An immunohistochemical analysis of the distribution of the neural tissue antigen G1N2 in the embryonic heart; implications for the development of the atrioventricular conduction system.

A monoclonal antibody raised against an extract from the Ganglion Nodosum of the chick and designated G1N2 proves to bind specifically to a subpopulation of cardiomyocytes in the embryonic human heart. In the youngest stage examined (Carnegie stage 14, i.e., 4 1/2 weeks of development) these G1N2-expressing cells are localized in the myocardium that surrounds the foramen between the embryonic left and right ventricle. In the lesser curvature of the cardiac loop this "primary" ring occupies the lower part of the wall of the atrioventricular canal. During subsequent development, G1N2-expressing cells continue to identify the entrance to the right ventricle, but the shape of the ring changes as a result of the tissue remodelling that underlies cardiac septation. During the initial phases of this process the staining remains recognizable as a continuous band of cells in the myocardium that surrounds the developing right portion of the atrioventricular canal, subendocardially in the developing interventricular septum and around the junction of the embryonic left ventricle with the subaortic portion of the outflow tract. During the later stages of cardiac septation, the latter part of the ring discontinues to express G1N2, while upon the completion of septation, no G1N2-expressing cardiomyocytes can be detected anymore. The topographic distribution pattern of G1N suggests that the definitive ventricular conduction system derives from a ring of cells that initially surrounds the "primary" interventricular foramen. The results indicate that the atrioventricular bundle and bundle branches develop from G1N2-expressing myocytes in the interventricular septum, while the "compact" atrioventricular node develops at the junction of the band of G1N2-positive cells in the right atrioventricular junction (the right atrioventricular ring bundle) and the ("penetrating") atrioventricular bundle. A "dead-end tract" represents remnants of conductive tissue in the anterior part of the top of the interventricular septum. The location of the various components of the avian conduction system is topographically homologous with that of the G1N2-ring in the human embryonic heart, indicating a phylogenetically conserved origin of the conduction system in vertebrates.

Antigens↗

Direct-developing sea urchins and the evolutionary reorganization of early development.

The evolution of development can be made accessible to study by exploiting closely related species that exhibit distinct ontogenies. The direct-developing sea urchin Heliocidaris erythrogramma is closely related to indirect-developing sea urchins that develop via a feeding larval stage. Superficial consideration would suggest that simple heterochronies resulting in loss of larval features and acceleration of adult features could explain the substitution of direct for indirect development. However, our experiments show that early development has in fact been extensively remodeled, with modified localization of maternal determinants coupled with dissociation of cell cleavage from axis formation resulting in novel patterns of cell lineage differentiation and fate map. Gene expression has undergone concomitant changes.

Animals↗

Strategy and planning for chemopreventive drug development: clinical development plans II.

This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs.

Animals↗

Developing oligodendroglia express mRNA for insulin-like growth factor-I, a regulator of oligodendrocyte development.

Insulin-like growth factors IGF-I and IGF-II are potent inducers of oligodendrocyte development. Because IGF-I is produced, in some cases, by the same cells that respond to it (autocrine/paracrine action), we examined the possibility that IGF-I is expressed by developing oligodendroglial cells. We employed a sensitive method, reverse transcriptase-polymerase chain reaction (RT-PCR), to detect IGF-I mRNA in purified populations of oligodendroglial cells isolated from rat brain during the period of oligodendrocyte development. Cells were purified by fluorescence activated cell sorting (FACS), using antibodies to the cell surface antigenic markers O4 and galactocerebroside (GC). RNA was isolated from the sorted cells, reverse-transcribed, and PCR-amplified, using a strategy that recognizes IGF-I mRNA but not DNA. The amplified band was identified as IGF-I by size, hybridization to an IGF-I-specific antisense probe, and restriction analysis. IGF-I mRNA was detected in O4-positive/GC-negative oligodendrocyte precursors and, more weakly, in GC-positive oligodendrocytes. IGF-I mRNA could be detected reproducibly in RNA extracted from 100-cell samples of O4-positive cells, making it unlikely that the mRNA was derived from contaminants in the FACS-sorted cell populations. We conclude that IGF-I is expressed by developing oligodendroglia. Autocrine expression of IGF-I by developing oligodendroglial cells suggests that oligodendrocyte development is, in part, autoregulatory.

Animals↗