9,011 research outputs found
Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice.
Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism
Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?
Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs
Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas
Neglected tropical diseases (NTDs) have\ud
been recently identified as significant public\ud
health problems in Texas and elsewhere in\ud
the American South. A one-day forum on the\ud
landscape of research and development and\ud
the hidden burden of NTDs in Texas\ud
explored the next steps to coordinate advocacy,\ud
public health, and research into a\ud
cogent health policy framework for the\ud
American NTDs. It also highlighted how\ud
U.S.-funded global health research can serve\ud
to combat these health disparities in the\ud
United States, in addition to benefiting\ud
communities abroad
The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination
Background:
Neglected tropical diseases (NTDs) are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward.
Results:
This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA), the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway.
Conclusion:
Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of NTDs, integrated mapping, rapid scale up of interventions and operational research into co implementation of intervention packages will be crucial
Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.
BackgroundNeural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.MethodsReplication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.ResultsOf the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.ConclusionsWe report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis
Epidemiologic aspects of neural tube defects in South East Iran
Objectives: To investigate the rate of neural tube defects (NTDs) and their relation to gender, maternal age, consanguineous marriage, season, and drug consumption in Birjand, Iran. Methods: This research was carried out on 16,785 live or stillborn newborns in Birjand, Iran from April 1997 to December 2001. Results: The rate of NTDs was 2.97 per 1000. This rate was 1.97 per 1000 in males, and 3.55 per 1000 in females. The rate of anencephaly was 1.37 per 1000, and spina bifida was 0.88 per 1000. We found that 32% of mothers with affected newborns had taken drugs during the first trimester of pregnancy, 90% of mothers did not consume folate before and during the first trimester, and 54% of parents had consanguineous marriage. Conclusion: We concluded that folate deficiency, usage of drugs during pregnancy, and consanguineous marriage may play a role of predisposition to NTD
Serum copper concentration in newborns with neural tube defects in northern Iran; A case control study
Objective: This study was conducted to determine the eventual association between copper deficiency in newborns with neural tube defects (NTD) in Northern Iran. A high prevalence of neural tube defects has been reported from this region. Methods: This hospital based case control study was carried out on 13 newborns having neural tube defects and 35 healthy controls in Northern Iran during 2005-2006. Serum copper was measured by spectrophotometery. Findings: Serum copper level in newborns with NTD and healthy normal newborns was 16.5 (±7.2) μmol/l and 16.7 (±6.6) μmol/ l, respectively. In case group 38.5% of newborns and in control group 28.6% had copper deficiency. Logistic regression analysis showed no association between the presence of NTD and copper deficiency (OR:1.6, 95% CI=0.3-7.1, P=0.5). Conclusion: This study showed no association between NTD and copper deficiency in newborns. © 2009 by Center of Excellence for Pediatrics, Children's Medical Center, Tehran University of Medical Sciences, All rights reserved
Improper Supplementation Habits of Folic Acid Intake by Hungarian Pregnant Women: Improper Recommendations
Background: Neural tube defects (NTDs) are some of the most common congenital anomalies. Proper folic acid supplementation is a dominant risk factor, which has been shown to decrease the incidence of NTDs. In Canada, the incidence of neuroblastoma has presented a considerable decrease of 60% as a result of enrichment cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of folic acid intake by pregnant women on the incidence of NTDs and neuroblastoma. Methods: Regular folic acid intake has been recommended to pregnant women in Hungary since the eighties of the last century by health visitors eventually raking effect as an official protocol which had been released in 1997. During 2001, 2002 and 2003. folic acid intake habits of pregnant women were evaluated by health visitors, proving to be successful in collecting data front 95.06% of the pregnant women. The incidence of NTDs has been registered by the Hungarian National Centre of Epidemiology, Department of Human Genetics and Teratology. The Pediatric Cancer Registry provided the incidence of neuroblastoma in children. Results: Consistent findings revealed a regular intake of supplementary folic acid products by 68.71% of the pregnant women. Out of these. 93.13% of pregnant women who were taking folic acid, started the supplementation after their 7 weeks of pregnancies, a time designated as the completion period of the development of the neural tube. The dose of folic acid supplementation was evaluated as less than 5 mg/day in 84.75% of the pregnant women. In Hungary, the incidence of NTDs has remained constant, while the incidence of neuroblastoma has shown constant slight increase in spite of the introduction of folic acid supplementation in 1997. Conclusions: Based on our experience, folic acid supplementation was initiated after the recognition of pregnancy and its application in a dose of lower than 5 mg/day neither decreased the incidence of NTDs nor did it have an effect on the neuroblastoma incidence. It is implicated that proper folic acid supplementation, which is started front the conception. can be achieved only with the enrichment of cereal grain flours
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