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Developmental Dynamics : An Official... Jun 2024The Wnt signaling pathway is highly conserved in metazoans and regulates a large array of cellular processes including motility, polarity and fate determination, and...
BACKGROUND
The Wnt signaling pathway is highly conserved in metazoans and regulates a large array of cellular processes including motility, polarity and fate determination, and stem cell homeostasis. Modulation of the actin cytoskeleton via the non-canonical Wnt pathway regulate cell polarity and cell migration that are required for proper vertebrate gastrulation and subsequent neurulation. However, the mechanism(s) of how the non-canonical pathway mediates actin cytoskeleton modulation is not fully understood.
RESULTS
Herein, we characterize the role of the Formin-homology protein; dishevelled associated activator of morphogenesis 2 (Daam2) protein in the Wnt signaling pathway. Co-immunoprecipitation assays confirm the binding of Daam2 to dishevelled2 (Dvl2) as well as the domains within these proteins required for interaction; additionally, the interaction between Daam2 and Dvl2 was Wnt-regulated. Sub-cellular localization studies reveal Daam2 is cytoplasmic and regulates the cellular actin cytoskeleton by modulating actin filament formation. During Xenopus development, a knockdown or loss of Daam2 specifically produces neural tube closure defects indicative of a role in non-canonical signaling. Additionally, our studies did not identify any role for Daam2 in canonical Wnt signaling in mammalian culture cells or the Xenopus embryo.
CONCLUSIONS
Our studies together identify Daam2 as a component of the non-canonical Wnt pathway and Daam2 is a regulator of neural tube morphogenesis during vertebrate development.
PubMed: 38877839
DOI: 10.1002/dvdy.720 -
Birth Defects Research Jun 2024To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR...
OBJECTIVE
To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs).
METHODS
ARA, EPA, and DHA composition was assessed using capillary gas chromatography.
RESULTS
ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels.
CONCLUSIONS
More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.
Topics: Humans; Eicosapentaenoic Acid; Docosahexaenoic Acids; Female; Neural Tube Defects; Arachidonic Acid; Folic Acid; Adult; Tunisia; Methylenetetrahydrofolate Reductase (NADPH2); Homocysteine; Pregnancy; Vitamin B 12; Case-Control Studies; Genotype; Vitamin D
PubMed: 38877667
DOI: 10.1002/bdr2.2372 -
Pediatric Surgery International Jun 2024To determine the relationship between preoperative nutritional status assessed using anthropometric measures and postoperative complications in pediatric surgical... (Observational Study)
Observational Study
AIM
To determine the relationship between preoperative nutritional status assessed using anthropometric measures and postoperative complications in pediatric surgical patients.
METHODOLOGY
This prospective observational cohort study included 650 patients from 6 months to 18 years undergoing elective surgery at our institution. Elective surgery included procedures such as herniotomy, orchidopexy, urethroplasty, cystoscopy, PUV fulguration, pyeloplasty, ureteric reimplantation, stoma formation/closure, anorectoplasty, pull-through, choledochal cyst excision and repair, VP shunt insertion, lipomyelomeningocele repair, diastematomyelia excision and repair, and cyst excision. Nutritional status was standardized using Z scores for weight, length, and BMI. Patients were monitored for a month following surgery to detect any complications, and they were classified into five grades using the Clavien-Dindo classification. The duration of hospital stays and readmission within 30 days following discharge were secondary outcomes.
RESULTS
There were 627 patients of both sexes involved in the study: 350 patients aged 6 months to 5 years (Group A), while 277 were aged between 5 and 18 years (Group B). Wasting status was 47.71% in Group A and 41.52% in Group B. In Group A, 40% of patients were stunted, while 83.75% were in Group B. Group A had 57.14% underweight patients. The complication rate was 39.14% in Group A and 38.99% in Group B. The incidence of postoperative complications was not significantly different in malnourished patients. The patients with prolonged duration of surgery (> 2 h) developed more complications in both groups (Group A-67.2%, Group B-82.6%; p < 0.0001). In addition, the patients who experienced complications had lengthier hospital stays (p < 0.001 in both groups) and increased readmission rates (p = 0.016 in Group A and p = 0.008 in Group B).
CONCLUSION
In our study, half of the patients in Group A and nearly two-third in Group B were malnourished. The preoperative poor nutritional status based on anthropometric parameters is not associated with increased postoperative complications. Randomized control trials linking preoperative malnutrition based on anthropometric measures and clinical outcomes in pediatric surgery patients are necessary to provide more robust information on this subject.
Topics: Humans; Postoperative Complications; Male; Female; Child; Prospective Studies; Adolescent; Child, Preschool; Infant; Nutritional Status; Anthropometry; Length of Stay; Elective Surgical Procedures; Preoperative Period
PubMed: 38871828
DOI: 10.1007/s00383-024-05736-7 -
Zhongguo Yi Liao Qi Xie Za Zhi =... May 2024To select high-quality and cost-effective dural (spinal) membrane repair materials, in order to reduce the cost of consumables procurement, save medical insurance funds,...
OBJECTIVE
To select high-quality and cost-effective dural (spinal) membrane repair materials, in order to reduce the cost of consumables procurement, save medical insurance funds, and optimize hospital operation and management.
METHODS
Taking the BS06B disease group (spinal cord and spinal canal surgery without extremely severe or severe complications and comorbidities, mainly diagnosed as congenital tethered cord syndrome) as an example, a retrospective analysis was conducted on the relevant data of surgical treatment for congenital tethered cord syndrome conducted in our hospital from January 2021 to June 2023. Safety and efficacy indicators in clinical application (incidence of postoperative epidural hemorrhage, incidence of postoperative purulent cerebrospinal meningitis, incidence of cerebrospinal fluid leakage, surgical duration, and postoperative hospital stay) were compared.
RESULTS
There was no difference in safety and effectiveness between different brands of dura mater repair materials.
CONCLUSION
For the repair of small incisions in dura mater surgery, high-quality and cost-effective dura mater repair materials can be selected to reduce hospital costs and control expenses for the disease group.
Topics: Dura Mater; Retrospective Studies; Humans; Neural Tube Defects; Spinal Cord
PubMed: 38863099
DOI: 10.12455/j.issn.1671-7104.230638 -
FASEB Journal : Official Publication of... Jun 2024Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs)....
Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.
Topics: Inositol; Neural Tube Defects; Animals; Female; Mice; Pregnancy; Embryo, Mammalian; Maternal Nutritional Physiological Phenomena; Metabolome; Folic Acid
PubMed: 38855924
DOI: 10.1096/fj.202400206R -
Child's Nervous System : ChNS :... Jun 2024The objective of this study was to explore the effect of intraoperative neurophysiological monitoring (IONM) on tethered spinal cord release in children.
OBJECTIVE
The objective of this study was to explore the effect of intraoperative neurophysiological monitoring (IONM) on tethered spinal cord release in children.
METHODS
The clinical data of 454 children with tethered cord syndrome who underwent surgery for tethered cord release were retrospectively analyzed. The children were divided into two groups: the non-IONM group and the IONM group. SPSS 26.0 software was used for statistical analysis. The evaluation indices included the effective rate and incidence of new neurological dysfunction.
RESULTS
The short-term results showed that the effective rate of the non-IONM group was 14.8%, while that of the IONM group was 15.2%. Additionally, the incidence of new neurological dysfunction was 7.8% in the non-IONM group and 5.6% in the IONM group. However, there was no significant difference between the two groups (P > 0.05). The medium- to long-term follow-up had significant difference (P < 0.05), the response rate was 32.1% in the IONM group and 23.7% in the non-IONM group, and deterioration rates regarding neurological dysfunction were 3.3% in the IONM group and 8.5% in the non-IONM group.
CONCLUSION
This study revealed that the use of IONM does not significantly improve the short-term treatment effect of patients undergoing surgery for tethered cord release or reduce the short-term incidence of postoperative new neurological dysfunction. However, the medium- to long-term prognoses of patients in the IONM group were better than those of patients in the non-IONM group.
PubMed: 38850295
DOI: 10.1007/s00381-024-06483-9 -
Neurobiology of Disease Jun 2024Bioenergetics describe the biochemical processes responsible for energy supply in organisms. When these changes become dysregulated in brain development, multiple... (Review)
Review
Bioenergetics describe the biochemical processes responsible for energy supply in organisms. When these changes become dysregulated in brain development, multiple neurodevelopmental diseases can occur, implicating bioenergetics as key regulators of neural development. Historically, the discovery of disease processes affecting individual stages of brain development has revealed critical roles that bioenergetics play in generating the nervous system. Bioenergetic-dependent neurodevelopmental disorders include neural tube closure defects, microcephaly, intellectual disability, autism spectrum disorders, epilepsy, mTORopathies, and oncogenic processes. Developmental timing and cell-type specificity of these changes determine the long-term effects of bioenergetic disease mechanisms on brain form and function. Here, we discuss key metabolic regulators of neural progenitor specification, neuronal differentiation (neurogenesis), and gliogenesis. In general, transitions between glycolysis and oxidative phosphorylation are regulated in early brain development and in oncogenesis, and reactive oxygen species (ROS) and mitochondrial maturity play key roles later in differentiation. We also discuss how bioenergetics interface with the developmental regulation of other key neural elements, including the cerebrospinal fluid brain environment. While questions remain about the interplay between bioenergetics and brain development, this review integrates the current state of known key intersections between these processes in health and disease.
PubMed: 38849103
DOI: 10.1016/j.nbd.2024.106550 -
Child's Nervous System : ChNS :... Jun 2024Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications...
INTRODUCTION
Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications leading to chronic disability and mortality. Identifying prognostic risk factors for early outcomes is crucial for tailored intervention strategies.
METHODS
This prospective study involved newborns and infants diagnosed with MMC who underwent surgery between 2020 and 2023 at Urmia University of Medical Sciences. Demographic data and surgical outcomes were collected, and participants were followed up for six months. Statistical analyses were conducted using descriptive statistics, Chi-Square, and independent t-test.
RESULTS
The study included 29 MMC cases, with an incidence rate of 1.4 per 10,000 live births. Lesions were predominantly located in the lumbar spine. Although mortality rates appeared to increase with ascending lesion sites, this trend was not statistically significant. Short-term outcomes revealed high morbidity and mortality rates, with neurological deficits being the most prevalent complication. Multivariable analysis identified head circumference as a significant predictor of adverse outcomes (IRR = 1.37, 95% CI = 1.02 to 1.86, p = 0.04). Furthermore, an increase in birth weight was associated with a reduction in the incidence of requiring a ventriculoperitoneal shunt (IRR = 0.99, 95% CI = 0.998 to 0.999, p = 0.02).
CONCLUSION
This prospective study highlights prognostic risk factors for early outcomes in MMC patients, emphasizing the need for personalized intervention strategies. By addressing modifiable risk factors and implementing targeted interventions, healthcare providers can strive to improve outcomes and enhance the quality of life for MMC patients.
PubMed: 38847879
DOI: 10.1007/s00381-024-06455-z -
Acta Medica Philippina 2024We report the case of a 33-week-old female fetus born with craniorachischisis to a gravida 5, para 4 (3104) mother with no previous history of conceiving a child with a...
We report the case of a 33-week-old female fetus born with craniorachischisis to a gravida 5, para 4 (3104) mother with no previous history of conceiving a child with a neural tube defect. Craniorachischisis is characterized by anencephaly and an open defect extending from the brain to the spine and is the most severe and fatal type of neural tube defect. Although the cause of neural tube defects is hypothesized to be multifactorial and is usually sporadic, the risk is increased in neonates born to mothers with a family history or a previous pregnancy with neural tube defect, both of which are not present in the index case. This case is unique in that only during the fifth pregnancy did the couple conceive a child with a neural tube defect, emphasizing that folic acid supplementation, the sole preventive measure proven to decrease the risk of neural tube defects, remains to be important in the periconceptual period for all women of childbearing age.
PubMed: 38846167
DOI: 10.47895/amp.vi0.6712 -
Pediatrics Jul 2024Urinary tract infections (UTIs) are common, but overdiagnosed, in children with spina bifida. We sought to evaluate the diagnostic test characteristics of urinalysis...
OBJECTIVES
Urinary tract infections (UTIs) are common, but overdiagnosed, in children with spina bifida. We sought to evaluate the diagnostic test characteristics of urinalysis (UA) findings for symptomatic UTI in children with spina bifida.
METHODS
Retrospective cross-sectional study using data from 2 centers from January 1, 2016, to December 31, 2021. Children with myelomeningocele aged <19 years who had paired UA (and microscopy, when available) and urine culture were included. The primary outcome was symptomatic UTI. We used generalized estimating equations to control for multiple encounters per child and calculated area under the receiver operating characteristics curve, sensitivity, and specificity for positive nitrites, pyuria (≥10 white blood cells/high-powered field), and leukocyte esterase (more than trace) for a symptomatic UTI.
RESULTS
We included 974 encounters from 319 unique children, of which 120 (12.3%) met our criteria for UTI. Pyuria had the highest sensitivity while nitrites were the most specific. Comparatively, nitrites were the least sensitive and pyuria was the least specific. When the cohort was limited to children with symptoms of a UTI, pyuria remained the most sensitive parameter, whereas nitrites remained the least sensitive. Nitrites continued to be the most specific, whereas pyuria was the least specific. Among all encounters, the overall area under the receiver operating characteristics curve for all components of the UA was lower in children who use clean intermittent catheterizations compared with all others.
CONCLUSIONS
Individual UA findings have moderate sensitivity (leukocyte esterase or pyuria) or specificity (nitrites) but overall poor diagnostic accuracy for symptomatic UTIs in children with spina bifida.
Topics: Humans; Retrospective Studies; Cross-Sectional Studies; Urinary Tract Infections; Urinalysis; Female; Male; Child; Spinal Dysraphism; Child, Preschool; Adolescent; Infant; Carboxylic Ester Hydrolases; Sensitivity and Specificity; Pyuria; Nitrites; Meningomyelocele; ROC Curve
PubMed: 38845550
DOI: 10.1542/peds.2023-065192