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Progestogen-only contraceptives during lactation: II. Infant development. World Health Organization, Task Force for Epidemiological Research on Reproductive Health; Special Programme of Research, Development, and Research Training in Human Reproduction.

Growth, development and health of infants whose mothers used progestogen-only contraceptives during lactation were examined in a prospective, non-randomized study that was carried out in seven centres in five countries (Egypt, Thailand, Kenya, Chile and Hungary). The results on development are reported here. Breastfeeding women requesting effective contraception were admitted to the study at six weeks postpartum. Infants of acceptors of progestogen-only methods (pill, DMPA, NET-EN or NORPLANT implants) and non-hormonal methods (IUD, barrier methods or sterilization) formed the study groups. The follow-up was at monthly intervals until the end of the first postpartum year. At each visit, the infant examination included, among other things, a set of developmental tests covering the following areas: gross motor, vision and fine motor, hearing, language and concept development, and self help and social skills. Participating in the study were 2466 mother-infant pairs. The comparisons between the study groups were carried out within centres using life table methods and Cox-model analysis having the time to first passing the test as the criterion. There were altogether 247 comparisons between the study groups. Thirty-two (13%) of these comparisons showed statistically significant differences: 20 differences showed that the infants in the progestogen-only groups passed the tests at an earlier age and 12 at a later age than infants in the non-hormonal groups. Since no consistent trends were observed across the centres, we conclude that in this study the progestogen-only contraceptives used during lactation did not adversely affect infant development.

Adolescent↗

State of the science: violence prevention efforts in developing and developed countries.

Violence is an important global public health problem that claims the lives of over 1.6 million people each year and results in numerous other health and social consequences. It is also a preventable health problem. This paper provides an overview of the current status of prevention efforts in developing and developed countries, describes what is known about the effectiveness of different approaches and highlights some of the important challenges in building the evidence-base for violence prevention programmes. Research conducted to date shows an imbalance in the emphasis of prevention programmes across the different types of violence. This imbalance is reflected in the timing of response, the nature and level of influence of interventions and programmes and the outcomes studied. Promising and effective approaches have been identified, but many more still require rigorous testing, particularly in developing countries. The current state of the science in violence prevention reveals both progress and a number of remaining challenges.

Developed Countries↗

Development of the orangutan permanent dentition: assessing patterns and variation in tooth development.

This study examines dental formation and alveolar emergence in a large cross-sectional sample composed primarily of wild-reared orangutans (N = 89) in order to provide information on the development of the permanent dentition in this hominoid and to address questions of variation in individual tooth formation, between teeth and between individuals. All specimens have been radiographed in lateral aspect and stages of crown and root formation recorded for all teeth. The ranges of crown and root formation of I1(1), C1(1), P4(4), M2(2), and M3(3) have been calculated relative to the stage of M1(1) development within a specific tooth quadrant. Then, for each specimen, BMDP scatterplot and nonparametric statistics have been used to graph changes in stages of these teeth relative to M1(1) stages and to examine relationships between pairs of upper and lower dental counterparts and between teeth of each jaw. Results indicate 1) high correlations between upper and lower tooth pairs and between many of the permanent teeth within individuals, 2) a relatively large range of variability in individual tooth development (multistage ranges relative to M1(1)), 3) greater variation in root development at emergence than earlier reports, and 4) evidence of variability within the sequence emergence pattern of the orangutan.

Animals↗

Gonadal development and plasma steroid levels during pubertal development in captive-reared striped bass, Morone saxatilis.

Puberty is the period during which full sexual development occurs and the capacity to reproduce is acquired. Despite its importance, our understanding of the endocrine regulation of puberty in lower vertebrates is still limited. The objective of the present study was to describe the changes in gonadal development and plasma steroid levels in a relatively late maturing species, the striped bass, during the first four years of life. In about 65% of the females, puberty was initiated during the third year. Although gonadosomatic index (GSI) and oocyte diameter increased during this year, this first cycle was characterized by a heterogeneous population of developing oocytes, a relatively low mean maximum oocyte diameter, and an absence of yolk granules in the oocytes. Plasma 17beta-estradiol (E(2)) levels were low in all three-year-old fish, suggesting that an insufficient stimulation of vitellogenin production by E(2) may underlie the lack of vitellogenin incorporation into developing oocytes. All monitored parameters increased during the fourth year, but were still below the values attained by older females. In about 60% of the males, puberty was initiated during the first year and all males were mature by the third year. During the first two years, several immature males initiated spermatogenesis without reaching full maturity. In mature males, mean GSI, plasma testosterone, and 11-ketotestosterone levels increased simultaneously, reaching higher values each subsequent year. Our results indicate that, similar to the situation in mammals, more than one reproductive cycle is required in striped bass before complete adulthood is reached.

Animals↗

Relationship between cyclooxygenase 1 and 2 selective inhibitors and fetal development when administered to rats and rabbits during the sensitive periods for heart development and midline closure.

BACKGROUND: A review of the scientific literature suggested the occurrence of low-level incidences of ventricular septal defect (VSD) and midline defect (MD) in rat fetuses and diaphragmatic hernia (DH), VSD, and MD in rabbit fetuses after maternal exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, an NSAID that irreversibly inhibits cyclooxygenase 1 (COX-1) and COX-2, induces DH, VSD, and MD when administered as one dose during the sensitive periods of development in rats. Unlike aspirin, other NSAIDs, including selective COX-2 inhibitors, reversibly inhibit COX activity. To evaluate whether the dysmorphogenesis observed after maternal NSAID exposure correlates with COX-1 or COX-2 inhibition, a series of compounds with different capacities to inhibit COX-1 and COX-2 were administered to pregnant rats and rabbits during the sensitive period for heart development and midline closure. METHODS: The compounds selected, ranked from the most COX-2 selective to the most COX-1 selective based onCOX inhibition in a human whole blood assay, were CJ-19,209, meloxicam, diclofenac, diflunisal, ibuprofen, and ketorolac. Rat dams were treated on gestation days (GDs) 9 and 10, and rabbit does were treated on GDs 9, 10, and 11. The doses selected for evaluation represented the maximum tolerable dose for the compound, with the exception of CJ-19,209, which was dosed at 1000 mg/kg. Fetuses were collected by cesarean section on GDs 21 and 29 for rats and rabbits, respectively, and all fetuses were examined for external and visceral developmental anomalies. RESULTS: In rabbits, diflunisal induced DH, VSD, and MD (omphalocele) and single incidences of VSD and MD (gastroschisis) were noted in the ibuprofen group; no other developmental findings were associated with treatment. In rats, ibuprofen, diflunisal, and ketorolac induced increases in the incidence of VSD. In general the induction of developmental defects was associated with compounds that selectively inhibit COX-1 or have a high ratio of COX-1 to COX-2 inhibition. CONCLUSIONS: Inhibition of COX-1 may be involved in the disruption of heart development, whereas the selective inhibition of COX-2 (as assessed with CJ-19,209) appears to have no effect on heart development and midline closure in rats and rabbits.

Abdominal Wall↗

Disturbed root development of permanent teeth after pediatric stem cell transplantation. Dental root development after SCT.

BACKGROUND: Deficient dental root development has been reported after conventional pediatric anticancer therapy, but less information is available on stem cell transplantation (SCT) recipients. METHODS: Root-crown (R/C) ratios of fully developed permanent teeth were assessed from panoramic radiographs of 52 SCT recipients, who were treated when they were age < 10 years. Using standard deviation scores (SDSs), the authors compared the R/C ratios to the corresponding tooth and gender-specific values in a healthy population. The percentage of affected R/C ratios per individual was examined in a subgroup of 39 (SG39) patients with advanced tooth development. The effects of total body irradiation (TBI) and SCT age on the R/C ratios were studied in TBI and high-dose chemotherapy (HDC = non-TBI) groups and in 3 age groups (< or = 3.0 years, 3.1-5.0 years, > or = 5.1 years). RESULTS: Per individual, 77% of the fully developed permanent teeth were affected in SG39. At the tooth level, in 77% of the 945 teeth studied (52 patients), the R/C ratios were outside +/-2 SDSs. More teeth were affected in the TBI (85%) than in the non-TBI (55%) group (P < 0.001). The teeth of the patients who were ages 3.1-5.0 years old at SCT presented with the most severe aberrations of the R/C ratio (mean SDS = -4.4) whereas the teeth of the youngest (age < or = 3.0 years) and the oldest (age > or = 5.1 years) patients were equally affected (mean SDSs = -3.1 and -3.0, respectively). CONCLUSIONS: Disturbances of dental root growth always followed pediatric SCT. HDC alone intensely harmed root growth but TBI further increased the adverse effects that were most extensive in the patients 3.1-5.0 years at SCT. These sequelae should be taken into account during the lifelong dental follow-up to minimize the clinical consequences of dental injuries.

Adolescent↗

Development of species identification in ducklings. XIII: A comparison of malleable and critical periods of perceptual development.

The present experiments sought to determine the relationship of the malleable period--when the mallard duck embryo is most susceptible to alien forms of maternal auditory stimulation--to the critical period, when the embryo must hear its own vocalizations in order to respond normally to the species-typical maternal call after hatching. It was found that a preference for either a wood duck or a chicken maternal call could be induced in devocalized mallard duck embryos by exposing them to either alien call some time between day 24, 0600 to day 26, 0600 hrs. Further experiments showed the height of the malleable period to be between day 24, 1400 hrs and day 25, 0800 hrs of embryonic development. Since the embryonic critical period for maintenance of the species-typical maternal auditory preference spans day 24, 0800 hrs to day 26, 0800 hrs, the malleable period for the induction of a preference for species-atypical maternal stimulation falls inside the critical period. While it is often assumed that malleable and critical periods overlap, this is the first behavioral study to actually demonstrate the temporal relationship of the two periods. It would seem important to further examine malleable and critical periods of development in a broader array of developmental contexts and species to determine whether malleable periods for atypical or abnormal development and critical periods for species-typical or normal development always coincide.

Acoustic Stimulation↗

Toward a global picture of development: lessons from genome-scale analysis in Caenorhabditis elegans embryonic development.

Development is the result of complex events, including cascades of transcriptional programs and numerous molecular interactions. Traditionally, research focus has been given to the characterization of individual mutants, regulators, or interactions. With the availability of complete genome sequences and high-throughput (HT) experimental techniques, probing development on a system level has become feasible. Pioneering work initiated in invertebrate model systems such as Caenorhabditis elegans has provided first drafts of catalogs of essential components, transcriptional regulatory diagrams and molecular interaction networks underlying developmental processes. Integrating these drafts approximates a system-level picture of development and provides local models for protein/gene functions. Here we summarize the progress toward elucidating developmental processes on a system level, including the applications of genomic technologies and computational analyses. We discuss C. elegans embryonic development in case studies to illustrate how various HT approaches can be integrated and how biological insights can be gained from these approaches.

Animals↗

Natural killing and antibody-dependent cellular cytotoxicity in specific-pathogen-free miniature swine and germ-free piglets. II. Ontogenic development development of NK and ADCC.

The ontogenic development of natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) in germ-free and specific-pathogen-fee (SPF) miniature swine were compared. Activities of NK and ADCC were tested by a short-term (2.5 to 4 h) 51Cr-labelled human myeloid cell line K562 and TNP-conjugated human B-cell line SB as target cells for NK and ADCC, respectively. Animals obtained by aseptic hysterectomy 3-5 days prior to term showed ADCC activities similar to adult levels but lacked NK activity. Hysterectomy-derived piglets which were colostrum-deprived and maintained in germ-free isolators developed NK activity at 3-4 weeks of age. In comparison, naturally-farrowed, colostrum-fed piglets maintained in our SPF facility developed NK activity at 2-3 weeks of age. Thereafter, there was no significant difference in the levels of either NK or ADCC between germ-free and SPF animals. This suggests that microbial flora and environment do not affect the development of effector cells for ADCC but do play some role in the maturation of NK cells during ontogeny. The difference in ontogeny of NK an ADCC further support our previous suggestion that the effector cells for NK and ADCC in swine are distinct sub-populations.

Animals↗

Distribution and expression of two interactive extracellular matrix proteins, cytotactin and cytotactin-binding proteoglycan, during development of Xenopus laevis. I. Embryonic development.

An immunohistochemical study of the localization of cytotactin and cytotactin-binding (CTB) proteoglycan throughout embryonic development of the anuran Xenopus laevis reveals that both appear in a restricted pattern related to specific morphogenetic events. CTB proteoglycan expression is first detected during gastrulation at the blastopore lip. Later, it is seen in the archenteron roof around groups of cells forming the notochord, somites and neural plate. Cytotactin first appears after neurulation, and is restricted to the intersomitic regions. Both molecules appear along the migratory pathways of neural crest cells in the trunk and tail. Later, cytotactin is present at sites where neural crest cells differentiate, around the aorta and in the smooth muscle coat of the gut; CTB proteoglycan is absent from these sites. In the head, cytotactin is initially restricted to the regions between cranial somites, while CTB proteoglycan is distributed throughout the cranial mesenchyme. The expression of both molecules is later associated with key events in chondrogenesis during the development of the skull. After chondrogenesis, CTB proteoglycan is distributed throughout the cartilage matrix, while cytotactin is restricted to a thin perichondrial deposit. Both molecules are expressed in developing brain. These findings are compared to studies of the chick embryo and although distinct anatomical differences exist between frog and chick, the expression of these molecules is associated with similar developmental processes in both species. These include mesoderm segmentation, neural crest cell migration and differentiation, cartilage development, and central nervous system histogenesis.

Animals↗

Developing rod photoreceptors from normal and mutant Rd mouse retinas: altered fatty acid composition early in development of the mutant.

The phospholipid and fatty acid contents of developing rod photoreceptor cells were determined in dissociated photoreceptor cells obtained from normal mice and from rd mice exhibiting an inherited retinal degeneration. Photoreceptors were dissociated from retinas by mechanical agitation after mild protease treatment and characterized by light and electron microscopy. Phospholipid classes were isolated by thin-layer chromatography, and fatty acyl groups separated and quantitated by capillary gas-liquid chromatography. Developing photoreceptor cells of normal retinas accumulated all phospholipid classes, but in proportions which shifted with age. The mole % contents of phosphatidylcholine (PC) and phosphatidylinositol (PI) decreased with age, whereas phosphatidylethanolamine (PE) and phosphatidylserine (PS) increased. The content of the polyunsaturated fatty acid docosahexaenoate (22:6), expressed as nmol/microgram lipid phosphorus, increased rapidly during development, whereas arachidonate (20:4) content tended to decline. Mono-unsaturated fatty acid levels (palmitoleate, 16:1; oleate, 18:1) declined with age. Among saturated fatty acids, palmitate (16:0) decreased during normal development, whereas stearate (18:0) increased. The total mass of phospholipid/photoreceptor cell in the normal, adult mouse retina was estimated to be approximately 14 pg. The total phospholipid content and mole % distribution of individual phospholipid classes in immature rd photoreceptors were similar to values for normal cells. In contrast, significant changes in fatty acid composition were detected between immature rd cells and normal cells. Rd cells generally had higher levels of saturated (myristate, 14:0; palmitate, 16:0) and monounsaturated fatty acids (oleate, 18:1) and lower levels of polyunsaturated fatty acids (arachidonate, 20:4; docosahexaenoate, 22:6), suggesting that fatty acid metabolism is altered by expression of the rd gene and/or by the associated impairment of photoreceptor cell differentiation.

Animals↗

The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development.

We have used confocal microangiography to examine and describe the vascular anatomy of the developing zebrafish, Danio rerio. This method and the profound optical clarity of zebrafish embryos make it possible to view the entire developing vasculature with unprecedented resolution. A staged series of three-dimensional images of the vascular system were collected beginning shortly after the onset of circulation at 1 day postfertilization through early- to midlarval stages at approximately 7 days postfertilization. Blood vessels in every region of the animal were imaged at each stage, and detailed "wiring patterns" were derived describing the interconnections between every major vessel. We present an overview of these data here in this paper and in an accompanying Web site "The interactive atlas of zebrafish vascular anatomy" online at (http://eclipse.nichd.nih.gov/nichd/lmg/redirect.html). We find a highly dynamic but also highly stereotypic pattern of vascular connections, with different sets of primitive embryonic vessels severing connections and rewiring in new configurations according to a reproducible plan. We also find that despite variation in the details of the vascular anatomy, the basic vascular plan of the developing zebrafish shows strong similarity to that of other vertebrates. This atlas will provide an invaluable foundation for future genetic and experimental studies of vascular development in the zebrafish.

Angiography↗

Craniofacial development: the tissue and molecular interactions that control development of the head.

The molecular cascades that control craniofacial development have until recently been little understood. The paucity of data that exists has in part been due to the complexity of the head, which is the most intricate regions of the body. However, the generation of mouse mutants and the identification of gene mutations that cause human craniofacial syndromes, together with classical embryological approaches in other species, have given significant insight into how the head develops. These studies have emphasized how unique the head actually is, with each individual part governed by a distinct set of signalling interactions, again demonstrating the complexity of this region of the body. This review discussed the tissue and molecular interactions that control each region of the head. The processes that control neural tube closure together with correct development of the skull, midline patterning, neural crest generation and migration, outgrowth, patterning, and differentiation of the facial primordia and the branchial arches are thus discussed. Defects in these processes result in a number of human syndromes such as exencephaly, holoprosencephaly, musculoskeletal dysplasias, first arch syndromes such as Riegers and Treacher-Collins syndrome, and neural crest dysplasias such as DiGeorge syndrome. Our current knowledge of the genes responsible for these human syndromes together with how the head develops, is rapidly advancing so that we will soon understand the complex set of molecular and tissue interactions that build a head.

Animals↗

[Light microscopic studies on the development of Theileria annulata (Dschunkowsky and Luhs, 1904) in Hyalomma anatolicum excavatum (Koch, 1844). I. The development in the gut of engorged nymphs (author's transl)].

A laboratory strain of H. a. excavatum was selected on high susceptibility for T. annulata through several generations. Giemsa-stained smears and wet smears of gut and gut content were studied. After engorgement of erythrocytic stages of T. annulata by the nymphs the following development was observed: 1. Erythrocytic merozoites developed to slender, spindleshaped "microgamonts" in the gut 24 to 96 hours after repletion (p. repl.). Spherical stages with a conspicuous spike developed at the same time and earlier. The "microgamonts" then form up to 4 nuclei and several flagella-like appendices. Filiform "microgametes" obviously develop from the "microgamonts". In addition, spherical stages, i.e. "macrogametes", occur. 2. Spherical "zygotes" with a vacuole-like center appear in the epithelial cells of the gut from day 5 p. repl. These "zygotes" increase steadily in size and then stain more intensely up to day 12 p. repl. 3. From day 12 p. repl. the spherical "Zygotes" change to elongate forms by a continuing process of folding. Finally, from day 13 p. repl., they extend to clubshaped kinetes. These kinetes move actively by gliding within the gut cells and from day 17 p. repl. in the haemolymph. It could not be decided yet whether these kinetes are oo- or sporokinetes.

Animals↗

On the development of the cerebellum of the trout, Salmo gairdneri. V. Neuroglial cells and their development.

The neuroglia of the cerebellum of Salmo gairdneri Richardson, 1836, has been studied in mature and developing specimens with light and electron microscopy. The light microscopic observations were largely carried out on Golgi material. The cerebellum of the trout contains all of the neurologlial cell types described for the mammalian cerebellum, viz. ependymal cells, Golgi epithelial cells, velate protoplasmic astrocytes, smooth protoplasmic astrocytes and oligodendrocytes. In addition two types of glial elements, which combine characteristics of ependymal cells and of velate astrocytes, are found. These elements are designated as ependymoid astrocytes and astrocytoid ependymal cells. Smooth astrocytes and oligodendrocytes were observed only in later stages of development and possibly arise from the secondary matrix. The other glial cell types, as well as transitional forms between these types, are present in rather early stages, and show a similar ultrastructure. It is plausible that all these types develop from the glioblasts produced by the ventricular matrix layer. Many glial cells are radially oriented and keep in contact with the meningeal surface throughout development. The lattice formed by matrix cells in the earliest stages, and by glial cells and the axons of granule cells later on, plays a role in directing the migration of cells. Other functions of the glia, such as dividing the cerebellar cortex in synaptic compartments, are suggested. It may be concluded that the high degree of differentiation of the teleostean cerebellum is also reflected by the morphology of the neuroglia.

Animals↗

Developing an environmental indicator system for sustainable development in China: Two case studies of selected indicators.

Environmental indicator systems are a fundamental tool in quantifying the environmental component of sustainable development. They are useful because they quantify the status and trends of key environmental parameters and provide information on the environment that allows authorities and communities to make informed decisions. This article analyzes the basic framework for Chinese environmental indicator systems and presents a "core" set of environmental indicators. In our research, we used a theme approach to develop the environmental indicator systems. We performed two case studies of selected indicators. In the first, we used an urban ambient air pollution composite index and an urban ambient air pollution indicator for three main pollutants to examine trends in urban air pollution in China from 1990 to 2000 at regional and national levels. The results indicate that China has made some progress towards controlling urban air pollution, but must do more in order to reach acceptable pollution levels. We think that an aggregated index and disaggregated indicators have important complementary roles in the policy-making processes. In the second case study, we developed and constructed a grassland degradation index that aggregates information on the extent and severity of grassland degradation. Taking the Xilinhaote region of Inner Mongolia as the study area, we calculated this index by combining remote-sensing data, a geographical information system (GIS), and field investigation. Based on these results, we provide recommendations regarding further development and measurement of environmental indicators in China.

Air Pollutants↗

A quantitative study of the morphological development and bacterial colonisation of the gut of the tammar wallaby Macropus eugenii eugenii and brushtail possum Trichosurus vulpecula during in-pouch development.

We compared the rates of change of various morphological parameters of the stomach, small intestine, caecum and colon of tammar wallabies and brushtail possums with body mass during in-pouch development. These were correlated with changes in the numbers of bacterial species in the various gut segments. In the pouch-young of both species, the wet tissue masses of all gut segments increased with body mass in a positively allometric manner (i.e. with a body mass exponent > 1), suggesting that the mass of each component was disproportionately low at birth, but increased disproportionately rapidly postnatally. However, the lengths of the wallaby stomach and small intestine scaled isometrically with respect to body mass (i.e. with a body mass exponent around 0.33), which may indicate that the shape of these components changes to the adult form during early neonatal development. Conversely, the length of the caecum and colon of both wallabies and possums scaled in a positively allometric manner with respect to body mass, showing area to volume compensation. This may indicate a more general pattern of disproportionately rapid postnatal enlargement in areas that are distal to the principal sites of neonatal digestion (i.e. the stomach). The numbers of bacterial species present in the various gastrointestinal segments of both species were low in animals aged 100 days or less but there was a significant increase in microbial diversity in the caecum of brushtail possums aged over 100 days. The possum caecum also showed the greatest rate of increase in wet tissue mass relative to body mass. It is postulated that caecal development may act as a nidus for establishment of communities of commensal microflora in the developing marsupial.

Animals↗

Opercular development and ontogenetic re-organization in a direct-developing frog.

The direct-developing frog, Eleutherodactylus coqui, has eliminated the tadpole stage from its ontogeny, and lacks many larval characters. We demonstrate that the dermal folds of E. coqui are homologous with the opercular folds of metamorphosing frogs. In both E. coqui and its metamorphic counterparts the opercular folds grow over the developing forelimb before perforating to free the entrapped limb. Opercular perforation in E. coqui occurs even in the absence of the forelimb but shows no signs of thyroid hormone dependence. The condensation of E. coqui development appears due to the excision of the extended larval period of developmental stasis. Analysis of opercular development, when viewed in conjunction with other developmental characters, suggests the ontogenetic period in the ancestral Eleutherodactylus life-history from which the tadpole was likely eliminated.

Animals↗