Interactions between the Foot and the Head Patterning Systems in Hydra vulgaris

AbstractThe Cnidarian, hydra, is an appealing model system for studying the basic processes underlying pattern formation. Classical studies have elucidated much basic information regarding the role of development gradients, and theoretical models have been quite successful at describing experimental results. However, most experiments and computer simulations have dealt with isolated patterning events such as the dynamics of head regeneration. More global events such as interactions among the head, bud, and foot patterning systems have not been extensively addressed. The characterization of monoclonal antibodies with position-specific labeling patterns and the recent cloning and characterization of genes expressed in position-specific manners now provide the tools for investigating global interactions between patterning systems. In particular, changes in the axial positional value gradient may be monitored in response to experimental perturbation. Rather than studying isolated patterning events, this approach allows us to study patterning over the entire animal. The studies reported here focus on interactions between the foot and the head patterning systems in Hydra vulgaris following induction of a foot in close proximity to a head, axial grafting of a foot closer to the head, or doubling the amount of basal tissue by lateral grafting of an additional peduncle-foot onto host animals. Resulting positional value changes as monitored by antigen (TS19) and gene (ks1 and CnNK-2) expression were assessed in the foot, head, and intervening tissue. The results of the experiments indicate that positional values changed rapidly, in a matter of hours, and that there were reciprocal interactions between the foot and the head patterning systems. Theoretical interpretations of the results in the form of computer simulations based on the reaction-diffusion model are presented and predict many, but not all, of the experimental observations. Since the lateral grafting experiment cannot, at present, be simulated, it is discussed in light of what has been learned from the axial grafting experiments and their simulations

Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America [NCT00097149]

Background: The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally. Methods/Design: We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions. Discussion: Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight.Instituto Multidisciplinario de Biología Celula

Oral cleft prevention programa (OCPP)

Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion: The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women

Oral cleft prevention program (OCPP)

Abstract Background Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. ClinicalTrials.gov Identifier NCT0039791

The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

Background: Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.Methods: The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7 thand 28 thday of life. The primary outcomes were mortality between the 7 thand 28 thday of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.Results: There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.Conclusions: Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.Instituto Multidisciplinario de Biología Celula

Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America [NCT00097149]

BACKGROUND: The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally. METHODS/DESIGN: We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions. DISCUSSION: Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight

The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

<p>Abstract</p> <p>Background</p> <p>Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.</p> <p>Methods</p> <p>The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7^thand 28^thday of life. The primary outcomes were mortality between the 7^thand 28^thday of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.</p> <p>Results</p> <p>There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.</p> <p>Conclusions</p> <p>Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00097149">NCT00097149</a></p

PATTERN REGULATION AND PATTERN SPECIFICATION IN THE EMBRYONIC CHICK WING

In an effort to determine the key factors involved in the processes of pattern regulation and pattern specification in the embryonic chick limb, the response of chick limb bud cells to experimental perturbations was studied. The results obtained are discussed in light of two contrasting models which have been formulated to describe pattern regulation and pattern specification: the ZPA/progress zone model which is based on long-range signalling via a diffusible morphogen and an autonomous cell counting mechanism, and the polar coordinate model which is based on local cell-cell interactions and cell proliferation. Experimental results discussed here indicate that there are three key factors involved in determining whether and what supernumerary limb structures will form following the juxtaposition of normally non-adjacent limb bud tissue. These factors are the position of origin of the donor tissue, the position grafted in the host, and the orientation of the graft in the host. All of these factors suggest that the response of chick limb bud cells to normally non-adjacent neighbors in a result of local cell interactions and cell proliferation. It is concluded that a model like the polar coordinate model best describes the experimental results obtained. A diagrammatic polar coordinate model description of many grafting operations performed with the embryonic chick wing is presented, as well as a polar coordinate model description of normal chick limb development

Interactions between the Foot and Bud Patterning Systems inHydra vulgaris

AbstractIn the freshwater coelenterate, hydra, asexual reproduction via budding occurs at the base of the gastric region about two-thirds of the distance from the head to the foot. Developmental gradients of head and foot activation and inhibition originating from these organizing centers have long been assumed to control budding in hydra. Much has been learned over the years about these developmental gradients and axial pattern formation, and in particular, the inhibitory influence of the head on budding is well documented. However, understanding of the role of the foot and potential interactions between the foot, bud, and head patterning systems is lacking. The purpose of this study was to investigate the role of the foot in the initiation of new axis formation during budding by manipulating the foot and monitoring effects on the onset of first bud evagination and the time necessary to reach the 50% budding point. Several experimental situations were examined: the lower peduncle and foot (PF) were injured or removed, a second PF was laterally grafted onto animals either basally (below the budding zone) or apically (above the budding zone), or both the head and PF were removed simultaneously. When the PF was injured or removed, the onset of first bud evagination was delayed and/or the time until the 50% budding point was reached was longer. The effects were more pronounced when the manipulation was performed closer to the anticipated onset of budding. When PF tissue was doubled, precocious bud evagination was induced, regardless of graft location. Removal of the PF at the same time as decapitation reduced the inductive effect of decapitation on bud evagination. These results are discussed in light of potential signals from the foot or interactions between the foot and head patterning systems that might influence bud axis initiation

Application of neurodevelopmental screening to a sample of South American infants: the Bayley Infant Neurodevelopmental Screener (BINS)

Submitted by Sandra Infurna ([email protected]) on 2016-08-22T19:14:21Z No. of bitstreams: 1 eduardo7_castilla_etal_IOC_2012.pdf: 346304 bytes, checksum: d5dddb3a415aabfb31bb93ff23281ca0 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2016-08-22T19:26:52Z (GMT) No. of bitstreams: 1 eduardo7_castilla_etal_IOC_2012.pdf: 346304 bytes, checksum: d5dddb3a415aabfb31bb93ff23281ca0 (MD5)Made available in DSpace on 2016-08-22T19:26:52Z (GMT). No. of bitstreams: 1 eduardo7_castilla_etal_IOC_2012.pdf: 346304 bytes, checksum: d5dddb3a415aabfb31bb93ff23281ca0 (MD5) Previous issue date: 2012The University of Iowa. College of Nursing. Iowa City, IA, USA.The University of Iowa. College of Public Health. Iowa City, IA, USA.The University of Iowa. College of Education. Statistics Outreach Center. Iowa City, IA, USA.Southern Illinois University School of Medicine. Division of Developmental and Behavioral Pediatrics/Psychology. Springfield, IL, USA.Instituto Nacional de Genética Médica Populacional (INAGEMP) and Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC) at CEMIC: Centro de Educación Médica e Investigación Clínica. Buenos Aires, Argentina / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ, BrasilNational Institutes of Health. Eunice Kennedy Shriver National Institute of Child Health and Human Development. Developmental Biology, Genetics and Teratology Branch Center for Developmental Biology and Perinatal Medicine. Bethesda, MD, USA.RTI International, Research Triangle Park. NC, USA.The University of Iowa. Department of pediatrics, Iowa, USA.Objective—To evaluate the utility of the Bayley Infant Neurodevelopmental Screener (BINS), standardized in the US, for South American infants, 3 to 24 months of age. Method—Thirty-five physicians administered the BINS to 2,471 South American infants recruited during routine well-child visits, 578 (23%) from Brazil and 1,893 (77%) from six other South American countries. The BINS was translated into Spanish and Portuguese and participating physicians were trained to administer the BINS. Physician inter-rater agreement with training tapes was 84.4%; test-retest reliability for age item sets ranged from 0.80 to 0.93 (Pearson’s r). Infants were classified into being at low, moderate, or high risk for developmental delay or neurological impairment based on their total BINS score. The sample was stratified by infant’s age, sex and language (Spanish and Portuguese). The BINS scores were compared to the scores of the US infant sample used to standardize the BINS. Results—Female infants performed higher than male at 16 to 20 months and 21 to 24 months; male infant scores were more variable at 5 to 6 months. Scores on only two items were significantly different between Spanish and Portuguese speaking participants. South American scores were typically significantly higher than the US sample, and a lower proportion of infants were classified as being at high risk in the South American sample than in the US standardization sample. Conclusion—Overall, the results of this study indicate that the BINS is feasible and appropriate for neurodevelopmental screening in South America. Further studies are needed to confirm the BINS utility in South America, including its use with a clinical sample