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Acta Neurochirurgica Jun 2024Myelocele is a rare form of open spina bifida. Surgical repair is recommended prenatally or in the first 48 h. In some cases, the repair may be delayed, and specific...
BACKGROUND
Myelocele is a rare form of open spina bifida. Surgical repair is recommended prenatally or in the first 48 h. In some cases, the repair may be delayed, and specific surgical factors need to be considered.
METHOD
We give a brief overview of the surgical anatomy, followed by a description of the surgical repair of a thoracolumbar Myelocele in an 11-month-old child.
CONCLUSION
Surgical repair of the Myelocele stabilizes the neurological status, prevents local and central nervous system infections. The understanding of Myelocele anatomy enables its removal while preserving as much healthy tissue as possible and restoring normal anatomy.
Topics: Humans; Thoracic Vertebrae; Infant; Lumbar Vertebrae; Meningomyelocele; Neurosurgical Procedures; Treatment Outcome; Male; Spinal Dysraphism; Magnetic Resonance Imaging
PubMed: 38884665
DOI: 10.1007/s00701-024-06163-2 -
Phenomics (Cham, Switzerland) Apr 2024The Shroom (Shrm) family of actin-binding proteins has a unique and highly conserved Apx/Shrm Domain 2 (ASD2) motif. Shroom protein directs the subcellular localization... (Review)
Review
The Shroom (Shrm) family of actin-binding proteins has a unique and highly conserved Apx/Shrm Domain 2 (ASD2) motif. Shroom protein directs the subcellular localization of Rho-associated kinase (ROCK), which remodels the actomyosin cytoskeleton and changes cellular morphology via its ability to phosphorylate and activate non-muscle myosin II. Therefore, the Shrm-ROCK complex is critical for the cellular shape and the development of many tissues, including the neural tube, eye, intestines, heart, and vasculature system. Importantly, the structure and expression of Shrm proteins are also associated with neural tube defects, chronic kidney disease, metastasis of carcinoma, and X-link mental retardation. Therefore, a better understanding of Shrm-mediated signaling transduction pathways is essential for the development of new therapeutic strategies to minimize damage resulting in abnormal Shrm proteins. This paper provides a comprehensive overview of the various Shrm proteins and their roles in morphogenesis and disease.
PubMed: 38884059
DOI: 10.1007/s43657-023-00119-9 -
Research Square Jun 2024Mesenchymal stem cells (MSCs) from gestational tissues represent promising strategies for treatment of congenital malformations, but plasticity and required high-risk...
BACKGROUND
Mesenchymal stem cells (MSCs) from gestational tissues represent promising strategies for treatment of congenital malformations, but plasticity and required high-risk surgical procedures limit their use. Here we propose natural exosomes (EXOs) isolated from amniotic fluid-MSCs (AF-MSCs), and their mimetic counterparts (MIMs), as valid, stable, and minimally invasive therapeutic alternatives.
METHODS
MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. Physiochemical and molecular characterization was performed to compare them to EXOs released from the same number of cells. The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake (using two different cell types, fibroblasts, and macrophages) and mRNA functionality overtime in an experimental setting as well as in an , whole embryo culture using pregnant C57BL6 dams.
RESULTS
Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a 3-fold greater yield. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein (GFP) in macrophages and fibroblasts. An whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo.
CONCLUSIONS
The present data confirms the potential application of EXOs for the prenatal repair of neural tube defects and proposes MIMs as prospective vehicles to prevent congenital malformations caused by exposure to drugs.
PubMed: 38883749
DOI: 10.21203/rs.3.rs-4325422/v1 -
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