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Revue Medicale de Liege Sep 2020We report a case of a 35-year-old woman with recurrent lumbar pain and left cruralgia in a post-traumatic context, for which the scanner had made possible the fortuitous...
We report a case of a 35-year-old woman with recurrent lumbar pain and left cruralgia in a post-traumatic context, for which the scanner had made possible the fortuitous diagnostic of a congenital anomaly. The diagnosis of diastematomyelia, which is more frequent in utero, is rare in adulthood and results from the implementation of an iconographic assessment. We will present the major malformations that are associated with diastematomyelia and which could evoke the presence of this malformation. The management of the anomaly is still controversial and can lead, if not done properly, to invalidating neurological deteriorations.
Topics: Adult; Female; Humans; Low Back Pain; Neural Tube Defects
PubMed: 32909406
DOI: No ID Found -
EBioMedicine Sep 2023Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with...
BACKGROUND
Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model.
METHODS
C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5 mg/kg), or 5xDTG (12.5 mg/kg) both administered orally with 50 mg/kg tenofovir disoproxil fumarate 33.3 mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified.
FINDINGS
313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls.
INTERPRETATION
Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs.
FUNDING
This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network.
Topics: Female; Pregnancy; Humans; Mice; Animals; Incidence; Placenta; Mice, Inbred C57BL; Folic Acid; Folic Acid Deficiency; Neural Tube Defects; Disease Models, Animal; HIV Infections; Maternal-Fetal Exchange; Fetus; Ontario
PubMed: 37586112
DOI: 10.1016/j.ebiom.2023.104762 -
The Pan African Medical Journal 2022
Topics: Humans; Meningocele; Meningomyelocele; Spinal Dysraphism
PubMed: 36405669
DOI: 10.11604/pamj.2022.42.288.36209 -
Journal of Pediatric Rehabilitation... 2020Research supports a resilience-disruption model of family functioning in families with a child with spina bifida. Guidelines are warranted to both minimize disruption to... (Review)
Review
Research supports a resilience-disruption model of family functioning in families with a child with spina bifida. Guidelines are warranted to both minimize disruption to the family system and maximize family resilience and adaptation to multiple spina bifida-related and normative stressors. This article discusses the spina bifida family functioning guidelines from the 2018 Spina Bifida Association's Fourth Edition of the Guidelines for the Care of People with Spina Bifida, and reviews evidence-based directions with the intention of helping individuals with spina bifida achieve optimal mental health throughout their lifespan. Guidelines address clinical questions pertaining to the impact of having a child with spina bifida on family functioning, resilience and vulnerability factors, parenting behaviors that may facilitate adaptive child outcomes, and appropriate interventions or approaches to promote family functioning. Gaps in the research and future directions are discussed.
Topics: Adaptation, Psychological; Adolescent; Adult; Child; Child, Preschool; Family; Family Health; Female; Humans; Infant; Infant, Newborn; Male; Practice Guidelines as Topic; Resilience, Psychological; Spinal Dysraphism; Stress, Psychological; Young Adult
PubMed: 33285643
DOI: 10.3233/PRM-200720 -
International Journal of Molecular... Jan 2023Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction... (Review)
Review
Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction of genetic and environmental factors. It is well known that folate deficiency increases the incidence of NTDs; however, the underlying mechanism remains unclear. Folate deficiency not only causes DNA hypomethylation, but also blocks the synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) and increases uracil misincorporation, resulting in genomic instabilities such as base mismatch, DNA breakage, and even chromosome aberration. DNA repair pathways are essential for ensuring normal DNA synthesis, genomic stability and integrity during embryonic neural development. Genomic instability or lack of DNA repair has been implicated in risk of development of NTDs. Here, we reviewed the relationship between folate deficiency, DNA repair pathways and NTDs so as to reveal the role and significance of DNA repair system in the pathogenesis of NTDs and better understand the pathogenesis of NTDs.
Topics: Humans; Folic Acid; Neural Tube Defects; Folic Acid Deficiency; DNA Repair; DNA; Genomic Instability
PubMed: 36768542
DOI: 10.3390/ijms24032220 -
Nutrients Apr 2023Maternal dietary factors have been suggested as possible contributing influences for congenital anomalies (CAs). We aimed to assess the association between vitamin D... (Meta-Analysis)
Meta-Analysis Review
Maternal dietary factors have been suggested as possible contributing influences for congenital anomalies (CAs). We aimed to assess the association between vitamin D supplementation or vitamin D status (s-25OHD) during pregnancy and CAs in the offspring. A comprehensive literature search was conducted in the three electronic databases: PubMed, Embase, and Cochrane Library. Included studies were critically appraised using appropriate tools (risk of bias 2, ROBINS-I). A protocol was registered in the International Prospective Register of Systematic Reviews (CRD42019127131). A meta-analysis of four randomised controlled trials (RCTs) including 3931 participants showed no effect of vitamin D supplementation on CAs, a relative risk of 0.76 (95% CI 0.45; 1.30), with moderate certainty in the effect estimates by GRADE assessment. Of the nine identified observational studies, six were excluded due to a critical risk of bias in accordance with ROBINS-I. Among the included observational studies, two studies found no association, whereas one case-control study identified an association between s-25OHD < 20 nmol/L and neural tube defects, with an adjusted odds ratio of 2.34 (95% CI: 1.07; 5.07). Interpretation of the results should be cautious given the low prevalence of CAs, RCTs with onset of supplementation after organogenesis, and low-quality observational studies.
Topics: Female; Pregnancy; Humans; Vitamin D; Vitamins; Neural Tube Defects; Case-Control Studies; Dietary Supplements
PubMed: 37432271
DOI: 10.3390/nu15092125 -
Birth Defects Research Jan 2020Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly...
BACKGROUND
Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5-2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary neurulation events. This study aimed to assess protein acetylation contribution to early patterning of the central nervous system both in human and murine specimens.
METHODS
We used both human and mouse (Cited2 ) samples to analyze the dynamic acetylation of proteins during embryo development through immunohistochemistry, western blot analysis and quantitative polymerase chain reaction.
RESULTS
We report the dynamic profile of histone and protein acetylation status during neural tube closure. We also report a rescue effect in an animal model by chemical p53 inhibition.
CONCLUSIONS
Our data suggest that the p53-acetylation equilibrium may play a role in primary neurulation in mammals.
Topics: Acetylation; Anencephaly; Animals; Disease Models, Animal; Embryonic Development; Histone Acetyltransferases; Humans; Mammals; Mice; Neural Tube Defects; Neurulation; Repressor Proteins; Spinal Dysraphism; Trans-Activators; Transcription Factors; Tumor Suppressor Protein p53
PubMed: 31758757
DOI: 10.1002/bdr2.1618 -
Journal of Pediatric Rehabilitation... 2020Orthopedic or musculoskeletal problems are common in individuals with spina bifida. They can affect function and mobility and, in the case of spinal deformity, affect... (Review)
Review
Orthopedic or musculoskeletal problems are common in individuals with spina bifida. They can affect function and mobility and, in the case of spinal deformity, affect pulmonary function. We discuss the current treatment guidelines developed through collaboration with the Spina Bifida Association and the Orthopedics and Mobility working group using a specific methodology previously reported [1,2]. General considerations are discussed followed by evaluation and treatment guidelines for specific age ranges. References are provided where applicable, but where data is lacking treatment guidelines fall under the umbrella of clinical consensus. This leaves "research gaps" where areas of possible future study could be considered.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Musculoskeletal Diseases; Orthopedics; Practice Guidelines as Topic; Spinal Dysraphism; Young Adult
PubMed: 33252095
DOI: 10.3233/PRM-200750 -
Genesis (New York, N.Y. : 2000) Nov 2021Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex... (Review)
Review
Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex involving the interplay of genetic and environmental factors. Since nutrient deficiency is a risk factor and dietary changes are the major preventative measure to reduce the risk of NTDs, a more detailed understanding of how common micronutrient imbalances contribute to NTDs is crucial. While folic acid has been the most discussed environmental factor due to the success that population-wide fortification has had on prevention of NTDs, folic acid supplementation does not prevent all NTDs. The imbalance of several other micronutrients has been implicated as risks for NTDs by epidemiological studies and in vivo studies in animal models. In this review, we highlight recent literature deciphering the multifactorial mechanisms underlying NTDs with an emphasis on mouse and human data. Specifically, we focus on advances in our understanding of how too much or too little retinoic acid, zinc, and iron alter gene expression and cellular processes contributing to the pathobiology of NTDs. Synthesis of the discussed literature reveals common cellular phenotypes found in embryos with NTDs resulting from several micronutrient imbalances. The goal is to combine knowledge of these common cellular phenotypes with mechanisms underlying micronutrient imbalances to provide insights into possible new targets for preventative measures against NTDs.
Topics: Animals; Gene-Environment Interaction; Humans; Micronutrients; Neural Tube Defects
PubMed: 34665506
DOI: 10.1002/dvg.23455 -
Journal of Molecular Medicine (Berlin,... Sep 2022No highly specific and sensitive biomarkers have been identified for early diagnosis of neural tube defects (NTDs). In this study, we used proteomics to identify novel...
No highly specific and sensitive biomarkers have been identified for early diagnosis of neural tube defects (NTDs). In this study, we used proteomics to identify novel proteins specific for NTDs. Our findings revealed three proteins showing differential expression during fetal development. In a rat model of NTDs, we used western blotting to quantify proteins in maternal serum exosomes on gestational days E18, E16, E14, and E12, in serum on E18 and E12, in neural tubes on E18 and E12, and in fetal neural exosomes on E18. The expression of coronin 1A and dynamin 2 was exosome-specific and associated with spina bifida aperta embryogenesis. Furthermore, coronin 1A and dynamin 2 were significantly downregulated in maternal serum exosomes (E12-E18), neural tubes, and fetal neural exosomes. Although downregulation was also observed in serum, the difference was not significant. Differentially expressed proteins were further analyzed in the serum exosomes of pregnant women during gestational weeks 12-40 using enzyme-linked immunosorbent assays. The findings revealed that coronin 1A and dynamin 2 showed potential diagnostic efficacy during gestational weeks 12-40, particularly during early gestation (12-18 weeks). Therefore, these two targets are used as candidate NTD screening and diagnostic biomarkers during early gestation. KEY MESSAGES: We used proteomics to identify novel proteins specific for NTDs. CORO1A and DNM2 showed exosome-specific expression and were associated with SBA. CORO1A and DNM2 were downregulated in maternal serum exosomes and FNEs. CORO1A and DNM2 showed good diagnostic efficacy for NTDs during early gestation. These two targets may have applications as NTD screening and diagnostic biomarkers.
Topics: Animals; Biomarkers; Dynamin II; Female; Fetus; Humans; Microfilament Proteins; Neural Tube Defects; Pregnancy; Rats
PubMed: 35915349
DOI: 10.1007/s00109-022-02236-w