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Diarrhea in developed and developing countries: magnitude, special settings, and etiologies.

Diarrheal diseases are major causes of morbidity, with attack rates ranging from two to 12 or more illnesses per person per year in developed and developing countries. In addition, diarrheal illnesses account for an estimated 12,600 deaths each day in children in Asia, Africa, and Latin America. The causes of diarrhea include a wide array of viruses, bacteria, and parasites, many of which have been recognized only in the last decade or two. While enterotoxigenic Escherichia coli and rotaviruses predominate in developing areas, Norwalk-like viruses, Campylobacter jejuni, and cytotoxigenic Clostridium difficile are seen with increasing frequency in developed areas; and Shigella, Salmonella, Cryptosporidium species, and Giardia lamblia are found throughout the world. The rational management of infectious diarrhea requires the highly selective use of laboratory tests for these varied etiologic agents, depending on the clinical and epidemiologic setting. The purpose of this review is to provide an overview of the magnitude, special settings, and etiologies of diarrhea endemic to developed and developing countries. This information permits a practical approach to the diagnosis and management of common diarrheal illnesses in different settings.

Acquired Immunodeficiency Syndrome↗

Tropical diseases, pathogens, and vectors biodiversity in developing countries: need for development of genomics and bioinformatics approaches.

The world's biodiversity, including many infectious, parasitic disease agents and their vectors whose impact on both human and animal health is significant, is largely retained in the developing countries of the tropics. Owing to the number of species involved and the relatively low-level exploration of pathogens and vectors biodiversity, several organisms are still waiting to be discovered and consequently explored in terms of genomics. Although some parasitic species of humans and animals have been studied through genomics and bioinformatics approaches, a significant number of relevant species are still to be addressed. Through the use of modern technologies, such as genomics and bioinformatics, for assessment of biodiversity and targeting tropical diseases, other relevant advantages of these initiatives for developing countries would be technology transfer and capacity building. Consequently, these initiatives could be critical to the development of the respective countries. Moreover, intra- and interhemispheric scientific collaboration should be encouraged and supported to increase the chances for success. In Brazil, the Ministry of Science and Technology has stepped forward to further such initiatives, co-supporting collaborative genomics and bioinformatics projects. The need for the establishment of working groups on genomics and bioinformatics in developing countries as well as the improvement and strengthening of collaborative research projects between developed and developing countries is discussed from our point of view. As these discussions remain open to debate, we encourage colleagues to promote further discussion on the subject.

Animal Diseases↗

Hepatocellular carcinoma prevention: a worldwide emergence between the opulence of developed countries and the economic constraints of developing nations.

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm, the major cause of death in patients with liver cirrhosis, and the third most common cause of cancer-related death in the world. The geographic distribution of HCC varies significantly and 80% of cases occur in developing countries (Far East and South Asia) where the prevalence of viral hepatitis is higher. The treatment of HCC is difficult because most patients are diagnosed when the tumour is in an advanced stage and is not amenable to potential curative therapy, thus prevention is the key to reducing HCC and its related morbidity and mortality. HCC is unique among cancers, occurring mostly in patients with a known risk factor. Ninety percent of HCCs develop in the context of chronic liver diseases and mainly in patients with cirrhosis. Viral hepatitis is the most common cause of HCC worldwide, followed by alcoholic liver disease (ALD) and other causes such as non-alcoholic fatty liver disease (NAFLD), genetic haemocromatosis (GH) and primary biliary cirrhosis in an advanced stage (III-V). In certain areas of the People's Republic of China, exposure to aflatoxin and HBV infection are thought to be responsible for the extraordinary high risk of HCC. Substantial progresses in the prevention of virusl-related hepatitis (screening of blood units, use of disposable sanitary tools, HBV vaccination) have been achieved in developed countries, but in the same areas, alcohol- and dysmetabolism-related HCCs are emerging problems which require specific interventions in terms of public health measures. In developing countries, economic constraints limit the development of any program for the prevention of viral hepatitis transmission (including health education campaigns, healthcare politics, primary prevention and the improvement of hygienic and sanitary conditions). When viral liver disease is established, only a minority of patients are treated worldwide and benefit a possible preventive effect of medical treatment on HCC development. Thus the real contribution of medical treatment to HCC prevention in patients with chronic viral hepatitis is small. Great efforts are needed to identify more effective medical measures for primary and secondary prevention of HCC.

Antiviral Agents↗

Safe drinking water production in rural areas: a comparison between developed and less developed countries.

At the fundamental level, there are remarkable parallels between developed and less developed countries in problems of providing safe drinking water in rural areas, but of course, they differ greatly in degree and in the opportunities for resolution. Small water supplies frequently encounter difficulty accessing sufficient quantities of drinking water for all domestic uses. If the water must be treated for safety reasons, then treatment facilities and trained operating personnel and finances are always in short supply. Ideally, each solution should be sustainable within its own cultural, political and economic context, and preferably with local personnel and financial resources. Otherwise, the water supply will be continuously dependent on outside resources and thus will not be able to control its destiny, and its future will be questionable. The history of success in this regard has been inconsistent, particularly in less developed but also in some developed countries. The traditional and ideal solution in developing countries has been central water treatment and a piped distribution network, however, results have had a mixed history primarily due to high initial costs and operation and maintenance, inadequate access to training, management and finance sufficient to support a fairly complex system for the long term. These complete systems are also slow to be implemented so waterborne disease continues in the interim. Thus, non-traditional, creative, cost-effective practical solutions that can be more rapidly implemented are needed. Some of these options could involve: small package central treatment coupled with non piped distribution, e.g. community supplied bottled water; decentralized treatment for the home using basic filtration and/or disinfection; higher levels of technology to deal with chemical contaminants e.g. natural fluoride or arsenic. These technological options coupled with training, technical support and other essential elements like community commitment provide opportunities that should be explored both for rural small communities and in rapidly growing periurban areas in developing countries.

Developed Countries↗

Developing and maintaining of hemophilia programs in developing countries.

There are elements key to the success of developing and maintaining hemophilia programs in developing countries. Health care providers who are dedicated champions of hemophilia care are essential. Their training through the WFH International Hemophilia Training Centers brings them in contact with modern comprehensive care as well as establishes collegial linkages with treaters in developed centers. Affordable, safe, viral free coagulation products are essential for an effective hemophilia program. Developing essential for an effective hemophilia program. Developing countries may have to use intermediate purity products because of economic considerations, but technologies must be used which reduce the risk of viral contamination. Successful programs also result from linking to hemophilia programs with national health care initiatives. Hemophilia health care must be recognized as a priority within the developing country's health care system.

Developing Countries↗

Telemedicine and developing countries. A report of study group 2 of the ITU Development Sector.

While there are significant potential advantages and benefits from telemedicine, the evidence of its cost-effectiveness and sustainability is meagre. This is because much of the telemedicine activity so far has been in the form of pilot projects of demonstrations in universities and hospitals with subsidized funding from government or other sources. The number of self-sustaining, commercial applications of telemedicine is still very small. Telemedicine undoubtedly yields cost savings in certain circumstances, but often the savings and benefits accrue to those who do not have to pay for the service. Thus, few service providers have found a way to recover their costs (and make a profit) from those to whom they provide their service. Even fewer countries have actually budgeted for the provision of telemedicine as a service widely available to their citizens. Nevertheless, with the rapidly declining cost in hardware and telecommunications, the level of interest and the corresponding activity in telemedicine is rising rapidly. Most of the telemedicine experience to date has been in the industrialized world. It is apparent that the first requirement of developing countries is for more information about telemedicine, what it is, and how it might be able to help solve some of the shortages in medical and health care. Given the potential of telemedicine to facilitate the provision of medical information and health care in rural areas, it seems useful for developing countries to undertake pilot projects in order to evaluate its potential and cost-benefits. The results of such pilot projects could be part of the development of a national health for all policy which takes telemedicine into account. In view of the other priorities of developing countries, especially those of the least developed countries, financing telemedicine activity is likely to remain a challenge for some time to come. Funding from external donor agencies may well be necessary, but local commitment and participation in pilot projects is essential if the project is to have a chance of success. As telemedicine requires a multidisciplinary approach, the active participation of telecommunication operators must be assured. Despite some false starts in the deployment of telemedicine as a continuing service to the general population--as opposed to a few well-to-do clients--telemedicine has great potential to improve access to health care and to contain costs in developing countries.

Computer Communication Networks↗

Development of catecholaminergic neurons in the pond snail, Lymnaea stagnalis: I. Embryonic development of dopamine-containing neurons and dopamine-dependent behaviors.

The embryonic development of the catecholaminergic system of the pond snail, Lymnaea stagnalis, was investigated by using chromatographic and histochemical methods. High performance liquid chromatography suggested that dopamine was the only catecholamine present in significant concentrations throughout the embryonic development of Lymnaea. Dopamine first became detectable at about embryonic stage (E) 15 (15% of embryonic development) and then increased in amount during early development to reach about 120-140 fmol per animal by around E40. Dopamine content remained stable during mid-embryogenesis (E40-65), increased slowing for the next couple of days, and then increased rapidly to culminate at about 400 fmol per animal by hatching. The detection of aldehyde- and glyoxylate-induced fluorescence and of tyrosine hydroxylaselike immunoreactivity indicated that the first catecholaminergic cells appeared in the late trochophore or early veliger stage of embryonic development (E32-35). The paired perikarya of these transient apical catecholaminergic (TAC) neurons were located beneath the apical plate, remained outside of the central ganglia during embryogenesis, and no longer contained detectable catecholamines close to hatching. TAC neurons bore cilia on the ends of short processes that penetrated the overlying epithelium; their long processes branched repeatedly under the ciliated apical plate. Several smaller catecholaminergic cells first appeared in the anterior margin of the foot at a stage when the embryos began to metamorphose from the veliger form (E55). Similar bipolar cells later appeared in the tentacle and lips. The axons of all of these small peripheral cells projected centrally and terminated within the neuropil of different central ganglia. Central catecholaminergic neurons, including RPeD1, differentiated only after metamorphosis was complete (E75). Development of locomotor, respiratory, and feeding behaviors correlated with maturation of catecholaminergic neurons, as indicated by histology and chromatography.

Animals↗

EDTA stimulates cleavage stage bovine embryo development in culture but inhibits blastocyst development and differentiation.

Culture of bovine zygotes in medium SOFaa supplemented with 100 microM EDTA significantly increased cleavage rates during the first 72 hr of development compared to development in SOFaa. However, continued culture in the presence of EDTA for a further 72 hr (total of 6 days of culture) resulted in significantly reduced development to the morulae/blastocyst and blastocyst stages compared to culture without EDTA. Highest rates of development to the morulae/blastocyst stage (56.5%) and to the blastocyst stage (43.2%) were achieved when zygotes were cultured for 72 hr with EDTA before transfer to medium SOFaa without EDTA. Resultant blastocysts also had significantly increased blastocyst cell number and ICM cell number compared to those cultured without EDTA in the first 72 hr. EDTA was shown to inhibit glycolytic activity of the cleavage stage embryo, thereby preventing the premature stimulation of glycolysis and enhancing development. However, EDTA should not be used for the later stage embryo as the inhibition of glycolysis reduces energy production at the blastocyst stage and significantly inhibits inner cell mass development.

Animals↗

Limb development in a "nonmodel" vertebrate, the direct-developing frog Eleutherodactylus coqui.

Mechanisms that mediate limb development are regarded as highly conserved among vertebrates, especially tetrapods. Yet, this assumption is based on the study of relatively few species, and virtually none of those that display any of a large number of specialized life-history or reproductive modes, which might be expected to affect developmental pattern or process. Direct development is an alternative life history found in many anuran amphibians. Many adult features that form after hatching in metamorphic frogs, such as limbs, appear during embryogenesis in direct-developing species. Limb development in the direct-developing frog Eleutherodactylus coqui presents a mosaic of apparently conserved and novel features. The former include the basic sequence and pattern of limb chondrogenesis, which are typical of anurans generally and appear largely unaffected by the gross shift in developmental timing; expression of Distal-less protein (Dlx) in the distal ectoderm; expression of the gene Sonic hedgehog (Shh) in the zone of polarizing activity (ZPA); and the ability of the ZPA to induce supernumerary digits when transplanted to the anterior region of an early host limb bud. Novel features include the absence of a morphologically distinct apical ectodermal ridge, the ability of the limb to continue distal outgrowth and differentiation following removal of the distal ectoderm, and earlier cessation of the inductive ability of the ZPA. Attempts to represent tetrapod limb development as a developmental "module" must allow for this kind of evolutionary variation among species.

Animals↗

Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

Animals↗

Clonal analysis of corn plant development. I. The development of the tassel and the ear shoot.

The development of the tassel and the ear shoot has been investigated in corn (Zea mays L.). X irradiation of dry kernels and seedlings heterozygous for anthocyanin markers or for factors altering tassel and ear morphology results in the formation of clones (sectors) from cells of the apical meristem. Most tassels develop from 4 +/- 1 cells of the mature embryo. The expression of ramosa-1, tunicate, tassel seed-6, and vestigial is cell autonomous in the tassel. These genes act late in development and modify the developmental fate or decision of an individual clone and not of the whole group of cells producing a tassel. The ear shoot develops from lineages of one to three cells derived each from the L-I (outmost cell layer) and L-II (second cell layer) of the apical meristem. Typically the clones start in the ear shoot (in the husks and possibly in the cob), extend upward in an internode, continue along the margin of the leaf sheath or leaf blade at the node above, and terminate in this or the next higher leaf. The separation of lineages for ear shoot and internode occurs in the period around 13 days after sowing. The analysis of clonal boundaries shows that a small number of embryonic cells become isolated in their developmental capacity. This commitment process appears to be analogous to the process of compartmentation in the imaginal disks of fruit flies. The extent of proliferation of individual cells within a group of highly flexible and any particular clone does not generate a specific part of a tassel or an ear shoot. There must be cellular communication between various clones so that the overall size and morphology of an organ remain normal and more or less fixed. Thus the process of development in plants is also highly regulative in nature and shares many features in common with development in fruit flies.

Anthocyanins↗

Disasters and development: Part 2: Understanding and exploiting disaster-development linkages.

This lesson is a continuation of Disasters and Development: Part 2: Understanding and Exploiting Disaster-Development Linkages published in Prehospital and Disaster Medicine in Volume 17, Number 3. It identifies the goals of a specific damage mitigation project that can be incorporated into a regular development project and the mechanisms for obtaining the mitigation component of such a project. Mechanisms for assessing the success of such a project are discussed. It stresses the importance of the application of building codes, associated training programs, and more extensive use of zoning regulations in urban development that decrease the population at risk and the likelihood of damage to industrial facilities. Disasters can elevate the development potential of a society at risk for damage from a hazard. The political impact of damage and disruption can be a catalyst for change. Development opportunities often are compromised because of an excessive focus on relief assistance. Interventions designed to mitigate the damage from a given hazard are particularly effective when they focus on areas at particularly high risk for actualization of the hazard. Support from the private sector, including the non-formal sector, is a key element of successful reconstruction management. The period of recovery is an opportunity for general assistance to government with administrative procedures, including enhanced management training programs.

Disaster Planning↗

Research in epilepsy: development priorities for developing nations.

PURPOSE: To identify research priorities in epilepsy for developing nations. METHODS: A panel discussion with audience participation at the Indo-U.K. Workshop on Epilepsy. This included short presentations by panelists, the presentation of a research proposal, and debate on research priorities. RESULTS: The need to focus on primary-care populations; to use a multi-centre random block design; to incorporate rural areas and a service component; to study incidence, natural history, and aetiology; to focus on problems, such as cysticercosis, and to adopt a comprehensive public health-centred approach in doing so; to study disorders of local interest, such as hot water epilepsy; to pilot both pharmacological and nonpharmacological interventions; to incorporate comprehensive measures of cognition, behaviour, and psychosocial outcome in all studies; and to examine the role of novel diagnostic tools (imaging for example) and therapy (surgery for example) on cost were all outlined as priority areas. DISCUSSION: There is a felt need for greater and better-quality research output from the developing world. The development of uniform research protocols, the twinning of developed and developing nations for research, and training of developing nations' personnel are likely to increase research output in the years that come.

Developing Countries↗

Blastomere development after embryo biopsy: a new model to predict embryo development and to select for transfer.

One of the most important and unsolved problems in in-vitro fertilization is to decide which embryos are more suitable to implant and therefore should be transferred. We analysed the in-vitro development of isolated biopsied blastomeres and compared it to the development of the original embryo, in order to find a relationship that could show the embryo's potential future development and so increase implantation rates. A total of 66 normally fertilized human embryos were biopsied at the 6- to 10-cell stages. At day 6, blastomeres were counted by nuclear labelling. A total of 33 embryos (50%) reached the blastocyst stage. Of the isolated blastomeres, 63% divided and 53% cavitated over 3 days in culture. Of the blastomeres taken from embryos that developed to the blastocyst stage, 88% divided, 79% cavitated, 76% divided and cavitated and 9% neither divided nor cavitated. In those from arrested embryos, 39% divided (P < 0.001), 21% cavitated (P < 0.001), 15% divided and cavitated (P < 0.001) and 55% neither divided nor cavitated (P < 0.001). Blastomeres biopsied from embryos that reached the blastocyst stage showed a significantly higher proportion of division and cavitation than those originated from arrested embryos. Culture of the isolated blastomeres can demonstrate those embryos more likely to develop to the blastocyst stage and that are probably more suitable to implant. Cryopreserving biopsed embryos and culturing blastomeres would increase implantation rates. Embryos can then be selected according to the blastomere development and thawed for transfer in a future cycle.

Biopsy↗

Development of a culture medium (BECM-3) for porcine embryos: effects of bovine serum albumin and fetal bovine serum on embryo development.

Media are available that can deliver modest porcine embryonic development from a single-cell zygote to the blastocyst stage. However, few embryos develop to hatched blastocysts by Day 7 in vitro, indicating deficiencies in media that inhibit early embryonic development. A defined culture medium, Beltsville Embryo Culture Medium (BECM-3), was developed to support porcine zygote development to the blastocyst stage. When fetal bovine serum was added by late Day 5 (late morula/early blastocyst stage), 80% of total embryos cultured from Day 2 developed into hatched blastocysts by Day 8. There was also a significant increase in the mean cell number of blastocysts and hatched blastocysts when culture was performed in BECM-3-based media in the absence of BSA fraction V. These studies provide a chemically defined foundation for elucidating key developmental components of preimplantation pig embryos.

Animals↗

Development of a positive youth development program: helping parents to improve their parenting skills.

The Project PATHS (Positive Adolescent Training through Holistic Social Programs) is a positive youth development program that attempts to promote holistic development in adolescents in Hong Kong. In the Tier 2 Program of this project, social workers are expected to develop positive youth development programs for adolescents having greater psychosocial needs. They are required to submit proposals that will be evaluated in terms of whether the proposals are evidence based, and appropriate evaluation mechanisms are included. With reference to the literature on parental control processes that Chinese parents may be loose in their behavioral control and they tend to overemphasize academic excellence, it is argued that improvement of the parenting skills of parents of Chinese adolescents is an important area to be addressed. To facilitate social workers to prepare the related proposals, a sample proposal on how to improve the parenting skills of Chinese parents is described, including its conceptual framework, proposed program, and evaluation plan. It is argued that this supportive approach (i.e., preparation of a sample proposal) can help social workers to develop quality proposals on positive youth development programs in Hong Kong.

Adolescent↗

Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung.

Recent investigations have suggested an active role for endothelial cells in organ development, including the lung. Herein, we investigated some of the molecular mechanisms underlying normal pulmonary vascular development and their influence on epithelial branching morphogenesis. Because the lung in utero develops in a relative hypoxic environment, we first investigated the influence of low oxygen on epithelial and vascular branching morphogenesis. Two transgenic mouse models, the C101-LacZ (epithelial-LacZ marker) and the Tie2-LacZ (endothelial-LacZ marker), were used. At embryonic day 11.5, primitive lung buds were dissected and cultured at either 20 or 3% oxygen. At 24-h intervals, epithelial and endothelial LacZ gene expression was visualized by X-galactosidase staining. The rate of branching of both tissue elements was increased in explants cultured at 3% oxygen compared with 20% oxygen. Low oxygen increased expression of VEGF, but not that of the VEGF receptor (Flk-1). Expression of two crucial epithelial branching factors, fibroblast growth factor-10 and bone morphogenetic protein-4, were not affected by low oxygen. Epithelial differentiation was maintained at low oxygen as shown by surfactant protein C in situ hybridization. To explore epithelial-vascular interactions, we inhibited vascular development with antisense oligonucleotides targeted against either hypoxia inducible factor-1 alpha or VEGF. Epithelial branching morphogenesis in vitro was dramatically abrogated when pulmonary vascular development was inhibited. Collectively, the in vitro data show that a low-oxygen environment enhances branching of both distal lung epithelium and vascular tissue and that pulmonary vascular development appears to be rate limiting for epithelial branching morphogenesis.

Animals↗

Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development.

Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization. Although it is known that Gli transcription factors are key effectors of hedgehog signaling, it has not been established which Gli protein mediates Ihh activity in skeletal development. Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and maturation of chondrocytes, but only partially rescued the defects in osteoblast development and cartilage vascularization. Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization promoted osteoblast development in perichondrial progenitor cells. Our results not only establish Gli3 as a critical effector for Ihh activity in the developing skeleton, but also identify an osteogenic role for a vasculature-derived signal, which integrates with Ihh and Wnt signals to determine the osteoblast versus chondrocyte fate in the mesenchymal progenitors.

Animals↗