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Outcome in schizophrenia and related disorders compared between developing and developed countries. A recursive partitioning re-analysis of the WHO DOSMD data.

BACKGROUND: Data on the two-year pattern of course of illness have been collected in the WHO study of the Determinants of Outcomes of Severe Mental Disorder (DOSMD). These data are reanalysed using recursive partitioning, a method not yet applied to psychiatric data to test the hypothesis that subjects from participating centres in developing countries had better outcomes than those in developed countries. METHOD: Subjects were those from the DOSMD study for whom two-year follow-up data were available (n = 1056). The classification and regression trees recursive partitioning technique was used to examine the predictor variables associated with the outcome variable two year pattern of course. RESULTS: Pattern of course was best predicted by centre, but two developed centres (Prague and Nottingham) grouped with the developing country centres excluding Cali, having better outcomes than in the remaining developed country centres and Cali. Type of onset (insidious v. non-insidious) was the next strongest predictor, but its effect differed across these two centre groupings. Effects for some groups were modified by other predictor variables, including age, child and/or adolescent problems, and gender. CONCLUSIONS: The predominant predictor effects on two-year pattern of course continued to be centre and type of onset, but complex interactions between these variables and other predictor variables are seen in specific centre groupings not strictly defined by 'developing' and 'developed'.

Developed Countries↗

A comparison of the extent and impacts of sewage contamination on urban groundwater in developed and developing countries.

In much of the world urban groundwater is an important resource for domestic and industrial use. In many developing countries, groundwater taken directly (untreated) from individual springs and wells is the only option available to communities where comprehensive, reliable reticulated supply systems are absent. A common feature of urban groundwater in both developing and developed countries is contamination by sewage. Current and recent research is presented that shows sewer leakage impacts groundwater in developed countries whilst on-site sanitation contaminates groundwater in developing countries. In the latter case, the competing demands of sanitation and groundwater protection must be addressed. Limitations on the usefulness of accepted standard sewage indicator species in groundwater are also highlighted. As sewage contamination of groundwater is usually addressed only if an actual health risk is posed, it is vital both to developed and developing countries to understand the movement of actual pathogens in groundwater in the context of groundwater management. Further research is required on microbial survival and health risks posed by sewage contamination.

Cross-Cultural Comparison↗

[Causes of adult mortality in developing and developed countries with low mortality rates].

"In a certain number of developing countries, life expectancy levels now approach those of the developed world. But, though life expectancies at birth may be similar, the infant mortality rate in developing countries remains higher, but is compensated by a lower rate of mortality for adults. Is it to be expected that as infant mortality rates continue to decline, the developing countries will maintain their advantageous adult mortality rates and that life expectancy will forge ahead of the level achieved in developed countries?... To answer this question, recent trends in adult cause-specific mortality rates in four developing countries (Chile, Hong Kong, Mexico, and Costa Rica) were compared with those in three industrialized countries (France, Germany and Japan). The results were inconclusive. Whilst life expectancies in some of these countries may be expected to forge ahead (Chile, Hong Kong), in others the margin between their life expectancies and those of developed countries have already narrowed." (SUMMARY IN ENG)

Adult↗

The Minnesota Child Development Inventory: validity and reliability for assessing development in infancy.

The concurrent validity and reliability of the Minnesota Child Development Inventory (MCDI) was assessed by comparing the MCDI general development index score, and each of the seven subscale scores, with the mental and psychomotor age equivalents achieved on the Bayley Scales of Infant Development. In addition, the co-positivity, co-negativity, positive and negative predictive values of the MCDI in identifying infants with a mental development index (MDI), or psychomotor development index (PDI) of greater than 2 SD below the mean were assessed. Subjects were 101 infants (8 to 19 months old) who were seen at a neonatal developmental follow-up clinic after discharge from the neonatal intensive care unit. Correlations were obtained for the entire sample as well as for the two chronological age groups (i.e., 8 to 10 months and 17 to 19 months) within the sample. A strong correlation between the MCDI scales and the Bayley Mental and Psychomotor Scales was documented for the entire population as well as for the individual age groups. The overall validity of the MCDI in identifying infants with a MDI or PDI of greater than 2 SD below the mean was limited due to relatively poor co-positivity and positive predictive value. Although the MCDI may yield consistent information about the development of an infant's skills, this research suggests the MCDI has limited capacity to discern infants having delayed development.

Aptitude↗

Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: a possible signal for vessel development.

Hypoxia is a well-known signal for angiogenesis, but the recent proposal that hypoxia exists in developing embryonic tissues and that it induces vascular development remains to be proven. In the present study, we demonstrate the presence of hypoxia in normal developing embryos by means of a hypoxia marker, pimonidazole, and its associated antibody. Our data clearly show that hypoxia marker immunoreactivity was highly detected in developing neural tubes, heart, and intersomitic mesenchyme at an early stage of organogenesis, suggesting that hypoxia may exist in the early stages of embryo development. We also found that hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were spatiotemporally co-localized with possible hypoxic regions in embryos. Investigation of platelet endothelial cell adhesion molecule (PECAM) expression provides evidence that endothelial cells proliferate and form the vessels in the hypoxic region in developing organs. Furthermore, we found that hypoxia induced both HIF-1alpha and VEGF in F9 embryonic stem and differentiated cells. Thus, we suggest that hypoxia may exist widely in developing embryonic tissues and that it may act as a signal for embryonic blood vessel formation in vivo.

Animals↗

Development and DNA polymerase activities in cultured preimplantation mouse embryos: comparison with embryos developed in vivo.

Embryos from superovulated female mice that developed in vitro from the two-cell stage were compared with in vivo embryos with respect to yield of blastocytes, number and types of cells, morphology in histologic section, and DNA polymerase activities. Significantly more embryos developed into blastocytes in vitro (93%) than in vivo (18%). Inner cell mass (ICM) cells comprised approximately 30% of total cells in late morula/early blastocyst stage embryos developed either in vitro or in vivo. However, the in vitro embryos developed approximately half the number of total cells as in vivo embryos, did not develop endoderm, and did not develop abembryonic trophoblast cells with morphologic characteristics of late preimplantation in vivo embryos. DNA-dependent DNA polymerase activities in in vitro embryos decreased in correspondence with the decrease in cell number resulting in per cell levels comparable to in vivo embryos. In contrast, the poly (A).oligo(dT)-dependent DNA polymerase activity was the same in embryos developing either in vitro or in vivo, indicating different regulatory mechanisms for the two enzyme activities. A variety of nutrients and growth factors in the culture medium did not increase cell numbers or DNA polymerase activities in embryos cultured for 3 days; extending the culture an additional 24 hours resulted in a loss of ICM cells and decreases in both DNA polymerase activities. These results show that the retarded growth of embryos in vitro is equally distributed between ICM and trophoblast, is not reversed by culture conditions that include serum growth factors, and is not due to decreased cellular levels of DNA polymerase activities.

Animals↗

Rural development and primary health care in less developed countries.

The traditional approach has been to regard health activities as a small component of rural development programmes. Under the Primary Health Care approach health is seen as the lever for rural development. But there are tendencies in the implementation of Primary Health Care in less developed countries towards limiting the range of activities to preventive and curative personal health services and of denuding it of its community development orientation. This paper highlights some of the issues that seem to militate against the establishment of Primary Health Care with its full complement of rural development activities. These activities together with the preventive and curative personal health services undertaken in the framework of community development promise to lead to the achievement of the hitherto elusive goal of improving the socioeconomic and health status of the rural population of less developed countries.

Allied Health Personnel↗

Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex.

Motor development and cognitive development may be fundamentally interrelated. Contrary to popular notions that motor development begins and ends early, whereas cognitive development begins and ends later, both motor and cognitive development display equally protracted developmental timetables. When cognitive development is perturbed, as in a neurodevelopmental disorder, motor development is often adversely affected. While it has long been known that the striatum functions as part of a circuit with dorsolateral prefrontal cortex, it is suggested here that the same is true for the cerebellum and that the cerebellum may be important for cognitive as well as motor functions. Like prefrontal cortex, the cerebellum reaches maturity late. Many cognitive tasks that require prefrontal cortex also require the cerebellum. To make these points, evidence is summarized of the close co-activation of the neocerebellum and dorsolateral prefrontal cortex in functional neuroimaging, of similarities in the cognitive sequelae of damage to dorsolateral prefrontal cortex and the neocerebellum, of motor deficits in "cognitive" developmental disorders, and of abnormalities in the cerebellum and in prefrontal cortex in the same developmental disorders.

Cerebellum↗

Insulin-like growth factor (IGF)-I controls prostate fibromuscular development: IGF-I inhibition prevents both fibromuscular and glandular development in eugonadal mice.

Although antiandrogen therapy has been shown effective in treating prostatic tumors, it is relatively ineffective in treating benign prostatic hyperplasia (BPH). In an attempt to understand better the role of androgens in the development of the normal prostate and BPH, we studied the relative effects of testosterone and IGF-I on the development of the two compartments of the prostate in castrated IGF-I((-/-)) male mice. Here we report that IGF-I stimulated the development of the fibromuscular compartment, but testosterone inhibited it (stromal epithelial ratio 2.17 vs. 0.83, respectively; P < 0.001). Testosterone also impaired IGF-I induced insulin receptor substrate-1 phosphorylation and cell division, and increased apoptosis in fibromuscular tissue. In sharp contrast IGF-I and testosterone both stimulated the development of the glandular compartment individually and together. The combined effects were either additive or synergistic on compartment size, cell division, insulin receptor substrate-1 phosphorylation, and probasin production. Together they also had a greater inhibitory effect on apoptosis in gland tissue. To determine whether IGF-I inhibition would inhibit both fibromuscular and glandular compartments, we tested the effect of IGF binding protein-1 on prostate development in two different models: castrated Ames dwarf mice and eugonadal normal male mice. IGF binding protein-1 blocked bovine GH-induced fibromuscular and glandular development in both. It also inhibited epithelial cell division and increased apoptosis in both prostate compartments in the eugonadal mice. The observed discordance between IGF-I and testosterone control of prostate compartment development might explain the relative failure of 5alpha-reductase inhibition in BPH and why testosterone inhibition might theoretically reduce gland volume but increase fibromuscular tissue. The work also provides a rationale for considering IGF-I inhibition as therapy for BPH to reduce the size of both prostate compartments.

Androgen-Binding Protein↗

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

The proposed National Children's Study has helped raise awareness of the issues related to children's health and the importance of monitoring the growth and development of children from preconception through adulthood. Many genetic predispositions can adversely impact the normal development process, and various environmental exposures have been linked to adverse reproductive health in rodent models and a small number of accidental human exposures. To monitor reproductive health and identify adverse effects at the earliest possible juncture, investigators must develop a network of biomarkers covering all stages and aspects of reproductive development and function. Biomarkers are biological indicators that can be measured repeatedly and are informative on one or more aspects of biological development or function. They can range from the anatomical level down to the molecular level and may provide information on the nature of an exposure, the effect of an exposure, or the susceptibility of individuals or populations to the toxic effects of an exposure. In theory, biomarkers can be used to monitor a wide variety of conditions and responses ranging from abnormal development to early indicators of late-onset disease. The main stumbling block with this theory has been finding appropriate biomarkers for particular conditions and exposures. Such biomarkers must be easily accessible, robust, and sensitive. Ideally, they will be expressed across a large section of the population, and can be monitored quickly, easily, conveniently, and with minimal cost. In this review, we discuss some of the current and emerging biomarkers of human pubertal development.

Adolescent↗

Assembling a global vaccine development pipeline for infectious diseases in the developing world.

Commercial realities have drastically reduced private investment in the development of new public health tools, but increased awareness of this situation has resulted in the emergence of a variety of research-based, nonprofit organizations. We reviewed current vaccine developments and developed a framework for efficient research and development investments in this area. We have identified several key "push" and "pull" forces within the vaccine research and product development environment and have examined their impacts on the process. These forces affect the global vaccine pipeline, which is composed of all individual vaccine initiatives and global partnerships (i.e., stakeholders), All of these research and development stakeholders must work together to establish and promote a global, sustainable research and development pipeline that delivers optimal vaccines and immunization technologies.

Child↗

Perioperative death in Malaysia: the transition phase from a developing nation to a developed one.

This paper examines the surgical pathology associated with perioperative deaths in a country that is undergoing the transition from a developing to a developed nation status. The data from an ongoing nation-wide perioperative mortality study was prospectively collected for the period July 1996 to December 1997 and analyzed. The surgical pathology related to perioperative deaths in Malaysia is different from other developing and developed countries. While death from trauma and the late presentation of surgical conditions are similar to developing countries, infective gastrointestinal conditions were rarely encountered. Diseases associated with advanced age such as colorectal cancer, peptic ulcer, urological diseases and vascular conditions are beginning to emerge. As the country races towards a developed nation status, increasing life expectancy and changing life-styles are expected to influence the disease pattern. The planning of surgical facilities and manpower development must recognize the changes taking place.

Adolescent↗

Development of the nasal chemosensory organs in two terrestrial anurans: the directly developing frog, Eleutherodactylus coqui (Anura: Leptodactylidae), and the metamorphosing toad, Bufo americanus (Anura: Bufonidae).

Nearly all vertebrates possess an olfactory organ but the vomeronasal organ is a synapomorphy for tetrapods. Nevertheless, it has been lost in several groups of tetrapods, including aquatic and marine animals. The present study examines the development of the olfactory and vomeronasal organs in two terrestrial anurans that exhibit different developmental modes. This study compares the development of the olfactory and vomeronasal organs in metamorphic anurans that exhibit an aquatic larva (Bufo americanus) and directly developing anurans that have eliminated the tadpole (Eleutherodactylus coqui). The olfactory epithelium in larval B. americanus is divided into dorsal and ventral branches in the rostral and mid-nasal regions. The larval olfactory pattern in E. coqui has been eliminated. Ontogeny of the olfactory system in E. coqui embryos starts to vary substantially from the larval pattern around the time of operculum development, the temporal period when the larval stage is hypothesized to have been eliminated. The nasal anatomy of the two frogs does not appear morphologically similar until the late stages of embryogenesis in E. coqui and the terminal portion of metamorphosis in B. americanus. Both species and their respective developing offspring, aquatic tadpoles and terrestrial egg/embryos, possess a vomeronasal organ. The vomeronasal organ develops at mid-embryogenesis in E. coqui and during the middle of the larval period in B. americanus, which is relatively late for neobatrachians. Development of the vomeronasal organ in both frogs is linked to the developmental pattern of the olfactory system. This study supports the hypothesis that the most recent common ancestor of tetrapods possessed a vomeronasal organ and was aquatic, and that the vomeronasal organ was retained in the Amphibia, but lost in some other groups of tetrapods, including aquatic and marine animals.

Animals↗

A mutational analysis of conjugation in Tetrahymena thermophila. 2. Phenotypes affecting middle and late development: third prezygotic nuclear division, pronuclear exchange, pronuclear fusion, and postzygotic development.

Conjugation following pair formation in Tetrahymena can be divided into three distinct sequences of events: prezygotic development, postzygotic development, and exconjugant development. The decision to proceed with postzygotic development is governed by a developmental checkpoint occurring sometime during the middle stages of conjugation. A second developmental decision is made to initiate pair separation and exconjugant development. This paper examines the phenotypes of five newly isolated conjugation mutants (cnj6-cnj10) which affect middle and late events within the conjugation program. cnj6 mutants exhibit normal nuclear behavior throughout development up to and including differentiation of new macronuclear anlagen. Pairs arrest at this developmental endpoint, unable to dissociate. cnj7 and cnj8 eliminate the third prezygotic nuclear division and the first postzygotic nuclear division. All subsequent developmental events appear normal. cnj9 eliminates the second postzygotic nuclear division, and subsequently, new macronuclei fail to develop despite parental macronuclear degradation. cnj10 results in a pleiotropic phenotype characterized by failure of numerous events which all appear to involve nuclear-cytoskeletal interactions. These defects include nuclear selection (anchoring nuclei to the exchange junction), pronuclear exchange, pronuclear fusion, and anchoring postzygotic nuclear division products to the posterior cell cortex. These mutant phenotypes are used to draw inferences regarding developmental dependencies that govern a cell's entry into the postzygotic and exconjugant developmental programs.

Animals↗

The development of traffic and traffic safety in six developed countries.

Two models are presented, describing the development of traffic and traffic safety. Traffic volumes, measured by the total amount of vehicle kilometers per year, are expected to follow a sigmoid saturation curve over time. The logistic function is used to model this development. The fatality rate, the number of fatalities per vehicle kilometer, is chosen to measure safety. The (negative) exponential function is selected to model the fatality rates over time. It is argued that these two aspects of the traffic system are fundamental and that the development of the number of fatalities results by multiplication. Given this assumption, the fall in the number of fatalities, noticed in almost all developed countries after a steady increase until 1970, does not need a special explanation. It follows from the combination of the monotonically increasing traffic volumes and the monotonically decreasing fatality rates. The two parsimonious models fit the data fairly well for six developed countries. The parameters differ substantially between countries, but also show common features. It is found from the parameters of the logistic function, that for all countries the points of maximum increase in traffic volume coincide just after 1970, the moment of the energy crisis. It is concluded from this finding that the energy crisis was caused by the cumulating demands of the oil-consuming countries, resulting in a reaction of the oil-producing countries. From the parameters of the exponential function, it is found that there also is a common point of intersection for fatality rates around 1980. It is shown that the development of safety is directly related to the development of traffic. The ten-year delay is interpreted as the time necessary for planning and implementation of safety measures. Finally, a striking relation is found between the volume parameters and the fatality-rate parameters, suggesting that the number of fatalities is a function of the derivative of the amount of traffic in the mathematical sense.

Accidents, Traffic↗

The establishment of polarity by hippocampal neurons: the relationship between the stage of a cell's development in situ and its subsequent development in culture.

Neurons removed from the embryonic hippocampus and placed into culture develop structurally and functionally distinct axonal and dendritic processes. The central issue addressed in this study concerns the extent to which the sequence of events which results in the differentiation of neurites by hippocampal neurons in culture is influenced by the cell's state of development in situ. [3H]thymidine was administered to pregnant rats either on Embryonic Day 15 (E15) or on E18.5 to label hippocampal neurons at known stages of their development. All fetuses were sacrificed on E19. Some of the fetal brains were sectioned and examined by autoradiography to determine the location of labeled cells in the hippocampus. The remaining brains were used to prepare hippocampal cell cultures. Neurons labeled at E18.5 remained confined to the ventricular zone at E19. Those labeled at E15 had completed their migration to the cortical plate. Other data suggest that the former cells had not yet initiated process outgrowth, while the latter cells had begun to elaborate both axons and dendrites. When introduced into culture, both populations of cells developed axons and dendrites and both compartmentalized MAP2 to the dendritic domain. Moreover, despite marked differences in their developmental state at the time of introduction into culture, both underwent the same sequence of developmental events leading to axonal and dendritic development. In a few cases cells that incorporated [3H]thymidine in situ at E18.5 apparently underwent mitosis in culture. These neurons also developed axons and dendrites appropriately. These results indicate that hippocampal neurons become polarized in culture, even if they have never developed axons or dendrites in situ, and do so as efficiently as cells that have become polarized before being placed into culture. Moreover, they indicate that the same sequence of events leading to the establishment of polarity occurs for hippocampal neurons with different developmental histories prior to culturing.

Animals↗

Development and growth of mouse embryonic kidney in organ culture and modulation of development by soluble growth factor.

Differentiation of the metanephrogenic mesenchyme is triggered by an inductive tissue interaction between an inducer tissue and the mesenchyme. It is generally believed that the epithelial ureter bud acts as an inducer during in vivo development. In response to the inductive stimulus most of the mesenchymal cells convert into epithelial cells, while a small fraction differentiates into stromal cells. In vitro, differentiation of isolated mesenchyme to epithelium can be induced by a variety of embryonic tissues, but nothing is known about the molecular nature of the inducing stimulus. In recent years, large numbers of polypeptide growth factors have been described, which in addition to proliferative effects were shown to exert effects on a variety of biological phenomena such as chemotaxis, inflammation, tissue repair, or induction of embryonic development. We therefore analyzed whether growth factors in the absence of inducer tissue can induce isolated kidney mesenchyme to differentiate into epithelium or interstitium. As expected, both growth and differentiation into epithelium were stimulated by an inducer tissue, the spinal cord. We found that none of the various growth factors tested (including epidermal growth factor, transforming growth factors alpha and beta, insulin-like growth factors I and II, fibroblast growth factor, platelet-derived growth factor, and retinoic acid) could mimick the effect of an inducer tissue, although we tested the factors over a wide concentration range. One of the tested factors, epidermal growth factor (EGF) stimulated the mesenchymal cells to become stromal cells, although it could not stimulate development into epithelium. EGF could stimulate stromal development both when the mesenchyme was cultured in isolation and when the mesenchyme was stimulated by an inducer tissue to become epithelium. The expansion of the stromal compartment in response to EGF treatment occurred at the expense of the epithelial cells, but EGF could not completely suppress the formation of epithelium. These data suggest the presence of EGF receptors in the developing kidney, but since application of soluble EGF leads to abnormal development, soluble EGF cannot be the natural ligand. We suggest that locally produced mitogens with an EGF-like structure may regulate the relative amounts of stroma (interstitium) and epithelium in the developing kidney.

Animals↗

Sleep for development or development for waking?--some speculations from a human perspective.

The issue of the relationship between sleep and development could be posed in the following terms: (1) does sleep have a function for development? and (2) which is the specificity of sleep function during development? Is it possible to assess critical ages of emergence and decline of specific sleep functions? The results of recent investigations related to the so-called ontogenetic hypothesis for the function of rapid eye movement (REM) sleep will be reviewed; suggestions are put forward concerning the possible role of non-rapid eye movement (NREM) sleep. Because of the difficulties to provoke long-lasting sleep deprivation in humans during development, two different approaches were used. The results of one set of analyses concerned the secretion of growth hormone during sleep under normal and pathological conditions and the relationship between sleep organization and nutritional supply utilisation in infants and children. The second approach aimed at investigating the long-term development of children suffering from sleep abnormalities at earlier ages. Furthermore, the role of dreaming during development will be discussed. The data summarized here only partly support the function of sleep during development; we would like to underscore the difficulty to dissociate the function of sleep from that of waking.

Child↗