Burden of neural tube defects in India: a systematic review and meta-analysis.

BACKGROUND: One of the most common and serious congenital defects is neural tube defect (NTD) in India. The data about the NTDs in India is lacking. The objective of this meta-analysis is to provide an estimate of NTDs in India with regional variations. METHOD: This study was conducted by doing a literature search using PubMed (Medline) and Embase databases for studies published from their inception to 1 October 2023 by using relevant keywords. We have prepared our study protocol by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, and our study is registered in PROSPERO. Pooled prevalence was calculated by using the Der Simonian-Liard method and random effect model to find out the burden of NTD in India. Additionally, subgroup and sensitivity analyses were also performed. NHLBI (National Heart, Lung, and Blood Institute) tool was used for assessing the study quality. RESULTS: A total of 1129 articles were identified by using the predefined keywords in which 27 articles were selected which were fitting the selection criteria defined in our study. The prevalence of NTDs in our meta-analysis was found to be 9.46 per 1000 births with a 95% confidence interval of 8.01 to 10.91 per 1000 births with significant heterogeneity with I2 of 99.15%. CONCLUSION: Our study highlights the increasing trend of NTDs over the past decades, with significant regional variation in India. There is an urgent need for comprehensive prevention strategies such as advocacy and awareness, antenatal screening for NTDs, folic acid supplementation, and food fortification. Future research is required for identification and implementation for a target-based approach for region specific.

Glial fibrillary acidic protein immunopositive neuroglial tissues with or without ependyma-lined canal in spinal lipoma of filar type: Relationship with retained medullary cord.

Background: Retained medullary cord (RMC) and filar lipomas are believed to originate from secondary neurulation failure; filar lipomas are reported to histopathologically contain a central canal-like ependyma-lined lumen with surrounding neuroglial tissue with ependyma-lined central canal (NGT w/E-LC) as a remnant of the medullary cord, which is a characteristic histopathology of RMC. With the addition of glial fibrillary acidic protein (GFAP) immunostaining, we reported the presence of GFAP-positive NGT without E-LCs (NGT w/o E-LCs) in RMC and filar lipomas, and we believe that both have the same embryopathological significance. Methods: We examined the frequency of GFAP-positive NGT, with or without E-LC, in 91 patients with filar lipoma. Results: Eight patients (8.8%) had NGT w/E-LC, 25 patients (27.5%) had NGT w/o E-LC, and 18 patients (19.8%) had tiny NGT w/o E-LC that could only be identified by GFAP immunostaining. Combining these subgroups, 56% of the patients (n = 51) with filar lipoma had GFAP immunopositive NGT. Conclusion: The fact that more than half of filar lipomas have NGT provides further evidence that filar lipoma and RMC can be considered consequences of a continuum of regression failure that occurs during late secondary neurulation.

Dwelling proximity to wildfire and spina bifida risk in offspring.

OBJECTIVE: To evaluate the association between wildfire exposure in pregnancy and spina bifida risk. METHODS: This retrospective cohort study used the California Office of Statewide Health Planning and Development Linked Birth File with hospital discharge data between 2007 and 2010. The Birth File data were merged with the California Department of Forestry and Fire Protection data of the same year. Spina bifida was identified by its corresponding ICD-9 code listed on the hospital discharge of the newborn. Wildfire exposure was determined based on the zip code of the woman's home address. Pregnancy was considered exposed to wildfire if the mother lived within 15 miles of a wildfire during the pregnancy or within 30 days prior to pregnancy. RESULTS: There were 2,093,185 births and 659 cases of spina bifida between 2007 and 2010. The births were analyzed using multivariable logistic regression models and adjusted for potential confounders. Exposure to wildfire in the first trimester was associated with higher odds of spina bifida (aOR= 1.43 [1.11-1.84], p-value = 0.01). Wildfire exposure 30 days before the last menstrual period and during the second and third trimesters were not associated with higher spina bifida risk. CONCLUSION: Wildfire exposure has shown an increased risk of spina bifida during the early stages of pregnancy.

Use of 'stacked' dermal template: Biodegradable temporising matrix to close a large myelomeningocele defect in a newborn.

Background: Myelomeningocele is a severe and complex congenital malformation of the central nervous system. Failure of neural tube closure at around four weeks of gestation results in an open communication between the neural placode and the external environment with varied functional impairment. Surgery is usually required. Objectives: The primary goals of surgical management are to preserve neural function and minimise infection. Reconstruction is dependent upon the site and size of the defect as well as the quality of the surrounding soft tissues. Surgeons may employ a range of reconstructive techniques in order to achieve closure. Skin substitutes, also known as dermal regeneration templates, have also been utilised. Discussion: In our unit, we use NovoSorb Biodegradable Temporising Matrix to reconstruct full-thickness skin and soft tissue defects. It is a synthetic, biodegradable, dermal regeneration template, composed of polyurethane foam bonded to a transparent sealing membrane and typically requires a two stage reconstruction. Integration and vascularisation take approximately three weeks. After this time, the recipient wound bed is suitable for split thickness skin grafting. A further benefit of dermal regeneration templates is the possibility of 'stacking' layers, which serves to increase the thickness of the final construct and to minimise overall contour defects. The authors present the case of a one-day-old full-term neonate with a large lumbosacral myelomeningocele that was successfully managed with staged, stacked NovoSorb Biodegradable Temporising Matrix and split thickness skin grafting. The authors believe this is the first case in which a 'stacked' dermal regeneration templates has been used to achieve healing of a primary myelomeningocele defect. Lay Summary: Background: NovoSorb Biodegradable Temporising Matrix (BTM) is a dermal regeneration template (DRT) and is used to reconstruct wounds following full-thickness skin and soft tissue loss resulting from burn injury, trauma, infection or surgery. It is composed of 2-millimetre thick, synthetic, biodegradable polyurethane foam bonded to a transparent (non-biodegradable) sealing membrane. Like all DRTs, it acts as a scaffold for cellular integration and vascularisation to eventually form a 'neo-dermis'. This is usually apparent from around three weeks. A second stage procedure can then be performed, with removal of the outer sealing membrane and split thickness skin grafting of the vascularised layer.Objectives: Myelomeningocele is a severe and complex congenital malformation of the central nervous system and forms the group of anomalies commonly referred to as neural tube defects (NTDs). Neural tube closure usually occurs at around four weeks of gestation and failure to do so, results in an open communication between the neural placode and the external environment. The degree of functional impairment varies but can include: lower limb paralysis; sensory loss; bladder and bowel dysfunction. In order to preserve neural function and minimise the risk of infection, surgery is usually required to close the defect. Reconstruction is varied and is dependent upon the site and size of the defect as well as the quality of the surrounding soft tissues. The use of local flaps has the potential complication of skin necrosis. Muscle based flaps may be debilitating and limit future functionality and worsen postural development. We were presented with a one-day-old neonate with a large lumbosacral myelomeningocele. A DRT (NovoSorb BTM) was selected as the primary reconstruction. Firstly, selection provided relatively low risk, with minimal morbidity and preserved the full complement of flap based reconstructive options for a later stage should instrumentation be required. Secondly, NovoSorb BTM conferred a robust seal over the dural repair with no demonstrable cerebrospinal fluid leak. Thirdly, the ability to add layers ('stack') of NovoSorb BTM in stages, once integration and vascularisation of the previous layer is complete, allows reconstruction of deeper contour defects.Discussion: We have illustrated the successful use of NovoSorb BTM as a DRT to achieve closure of a large lumbosacral myelomeningocele without complication and with longstanding stability. We believe this technique provides reconstructive teams with an alternative option that is effective, safe and reproducible and which spares local tissues for future elective reconstructive procedures, should they be required.

Unruptured Myelomeningocele Closure Surgery: A Case Report.

Myelomeningocele (MMC) is an in-utero closure defect of the posterior portion of the neural tube, and it is the most common neural tube defect (NTD) compatible with life. It is usually associated with other congenital malformations, such as hydrocephalus and Chiari type 2 syndrome. Therefore, the long-term outcome depends on early repair, and the surgery is urgently scheduled. Newborns with MMC are a special population that requires meticulous preoperative preparation to maintain hemodynamic stability during the procedure and a favorable outcome. In this case report, we describe the challenges of unruptured myelomeningocele closure surgery in a newborn with 12 hours of life. This special case emphasizes the importance of a multidisciplinary approach between anesthesiologists, neurosurgeons, and plastic surgeons to provide the best care to this subset of patients.

A Devastating Diagnosis: Anencephaly With Unexpected Fetal Heartbeat.

This case report describes a severe birth defect called anencephaly in a fetus at 18 weeks of pregnancy. Anencephaly occurs when the upper part of the baby's brain and skull do not form correctly. This condition is usually detected earlier in pregnancy, often in the first three months. However, this case was discovered at 18 weeks, highlighting the need for careful monitoring throughout pregnancy. The unique aspect of this case is that most pregnancies with anencephaly do not progress this far. This later diagnosis provides important information about the different ways the condition can develop. By studying cases like this, healthcare providers can improve prenatal care and potentially detect such defects earlier, even in the later stages of pregnancy. Overall, this report emphasizes the importance of continuous monitoring during pregnancy and offers insights that could lead to better diagnosis, care, and support for families facing similar situations.

Cellular responses to developmental exposure to pyriproxyfen in chicken model: Contrasting embryos with and without exencephaly.

The insecticide pyriproxyfen (PPF), commonly used in drinking water, has already been described as a potential neurotoxic agent in non-target organisms, particularly during embryonic development. Consequently, exposure to PPF can lead to congenital anomalies in the central nervous system. Therefore, understanding the impact of this insecticide on developing neural cells is a relevant concern that requires attention. Thus, this study aimed to investigate the effects of PPF on the proliferation, differentiation, migration, and cell death of neural cells by comparing embryos that develop exencephaly with normal embryos, after exposure to this insecticide. Chicken embryos, used as a study model, were exposed to concentrations of 0.01 and 10 mg/L PPF on embryonic day E1 and analyzed on embryonic day E10. Exposed embryos received 50 µL of PPF diluted in vehicle solution, and control embryos received exclusively 50 µL of vehicle solution. After exposure, embryos were categorized into control embryos, embryos with exencephaly exposed to PPF, and embryos without exencephaly exposed to PPF. The results showed that although the impact was differentiated in the forebrain and midbrain, both brain vesicles were affected by PPF exposure, and this was observed in embryos with and without exencephaly. The most evident changes observed in embryos with exencephaly were DNA damage accompanied by alterations in cell proliferation, increased apoptosis, and reduced neural differentiation and migration. Embryos without exencephaly showed DNA damage and reduced cell proliferation and migration. These cellular events directly interfered with the density and thickness of neural cell layers. Together, these results suggest that PPF exposure causes cellular damage during neurogenesis, regardless of whether embryos display or do not display external normal morphology. This nuanced understanding provides important insights into the neurotoxicity of PPF and its potential effects on inherent events in neurogenesis.

In need of robust evidence of non-association of pregestational and early pregnancy SARS-CoV-2 infections with congenital anomalies.

SARS-CoV-2 infection during pregestational and early pregnancy periods has an unclear impact on fetal development. Although vertical transmission is rare, potential effects on the developing fetal brain are plausible. However, robust evidence linking maternal SARS-CoV-2 infection to congenital anomalies is limited due to inadequate tracking of infection history and methodological flaws in published studies. This is further complicated by limitations, such as restricted testing access and undiagnosed infections, particularly in low- and middle-income countries. Most data focus on hospitalized women near term, lacking information on first- and second-trimester infections. Thus, an accurate assessment of the impact of COVID-19 on congenital anomalies is essential. It should however be emphasised that we have robust evidence that vaccination against COVID-19 before or during early pregnancy is not associated with malformations, ruling out any role of COVID-19 vaccines in these increased rates of congenital abnormalities. This viewpoint discusses findings from surveillance registries, highlights study limitations, and offers research recommendations to inform clinical guidelines and public health strategies, aiming to mitigate the effects of viral infections on early neurodevelopment.

Congenital syndromic Chiari-like malformation (CSCM) in Holstein cattle: towards unravelling of possible genetic causes.

BACKGROUND: Chiari malformation type II (CMII) was originally reported in humans as a rare disorder characterized by the downward herniation of the hindbrain and towering cerebellum. The congenital brain malformation is usually accompanied by spina bifida, a congenital spinal anomaly resulting from incomplete closure of the dorsal aspect of the spinal neural tube, and occasionally by other lesions. A similar disorder has been reported in several animal species, including cattle, particularly as a congenital syndrome. A cause of congenital syndromic Chiari-like malformation (CSCM) in cattle has not been reported to date. We collected a series of 14 CSCM-affected Holstein calves (13 purebred, one Red Danish Dairy F1 cross) and performed whole-genome sequencing (WGS). WGS was performed on 33 cattle, including eight cases with parents (trio-based; group 1), three cases with one parent (group 2), and three single cases (solo-based; group 3). RESULTS: Sequencing-based genome-wide association study of the 13 Holstein calves with CSCM and 166 controls revealed no significantly associated genome region. Assuming a single Holstein breed-specific recessive allele, no region of shared homozygosity was detected suggesting heterogeneity. Subsequent filtering for protein-changing variants that were only homozygous in the genomes of the individual cases allowed the identification of two missense variants affecting different genes, SHC4 in case 4 in group 1 and WDR45B in case 13 in group 3. Furthermore, these two variants were only observed in Holstein cattle when querying WGS data of > 5,100 animals. Alternatively, potential de novo mutational events were assessed in each case. Filtering for heterozygous private protein-changing variants identified one DYNC1H1 frameshift variant as a candidate causal dominant acting allele in case 12 in group 3. Finally, the presence of larger structural DNA variants and chromosomal abnormalities was investigated in all cases. Depth of coverage analysis revealed two different partial monosomies of chromosome 2 segments in cases 1 and 7 in group 1 and a trisomy of chromosome 12 in the WDR45B homozygous case 13 in group 3. CONCLUSIONS: This study presents for the first time a detailed genomic evaluation of CSCM in Holstein cattle and suggests an unexpected genetic and allelic heterogeneity considering the mode of inheritance, as well as the type of variant. For the first time, we propose candidate causal variants that may explain bovine CSCM in a certain proportion of affected calves. We present cattle as a large animal model for human CMII and propose new genes and genomic variants as possible causes for related diseases in both animals and humans.

Epidemiology of neural tube defects in Finland: a nationwide register study 1987-2018.

BACKGROUND: Our aim was to evaluate the prevalence, mortality, regional and sex distribution of neural tube defects (NTDs) in Finland. METHODS: Data for this population-based study were collected from 1987 to 2018 from the national health and social welfare registers. RESULTS: There were in total 1634 cases of NTDs, of which 511 were live births, 72 pregnancies ended in stillbirth and 1051 were terminations of pregnancy due to fetal anomaly (TOPFA). The total prevalence of NTDs was 8.6 per 10 000 births and it increased slightly annually (OR 1.008; 95% CI: 1.002, 1.013) during the 32-year study period. The birth prevalence of NTDs decreased (OR 0.979; 95% CI: 0.970, 0.987), but the prevalence of TOPFA increased annually (OR 1.024; 95% CI 1.017, 1.031). The perinatal mortality of NTD children was 260.7 per 1000 births and the infant mortality was 184.0 per 1000 live births, whereas these measures in the general population were 4.6 per 1000 births and 3.3 per 1000 live births, respectively. There was no difference in the NTD prevalence between males and females (P-value 0.77). The total prevalence of NTDs varied from 7.1 to 9.4 per 10 000 births in Finland by region. CONCLUSIONS: Although the majority of NTDs are preventable with an adequate folic acid supplementation, the total prevalence increased in Finland during the study period when folic acid supplementation was mainly recommended to high-risk families and to women with folic acid deficiency. NTDs remain an important cause of infant morbidity and mortality in Finland.

Preconception Folic Acid and Multivitamin Supplementation for the Prevention of Neural Tube Defect: An Umbrella Review of Systematic Review and Meta-analysis.

BACKGROUND: Previous reviews explored the association between maternal use of folic acid and multivitamin supplements and risk of neural tube defect (NTD) in children, with no definitive conclusion. These reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review is to combine the inconsistent data on the effect of prenatal folic acid and/or multivitamin supplementation for the prevention of NTD in offspring. METHODS: Using the PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar reported that the effects of folic acid and/or multivitamin supplementation for the prevention of NTD in offspring were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. RESULT: Ten SRM with 296,816 study participants were included. The random-effects model analysis from 10 included systematic review and meta-analysis revealed that the pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD globally is found to be 0.43 (95% CI: 0.29, 0.58) (I2 = 93.50%; p ≤0.001). In the subgroup analysis, the pooled effect was found to be 0.23 (0.09, 0.37) in folic acid group, while this estimate is 0.63 (0.53, 0.72) and 0.61 (0.46, 0.75) in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50 (0.34, 0.66) in SRMs aimed at occurrence prevention (primary prevention) group, while this estimate is 0.20 (-0.01, 0.41) among SRMs, which aimed at reoccurrence (secondary) prevention, and 0.61 (0.46, 0.75) among those SRMs aimed to assess the effect folic acid or multivitamin for the prevention of both occurrence and reoccurrence. The pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD was found to be 0.45 (0.03, 0.87) in SRMs of observational studies, while this estimate is 0.43 (0.32, 0.54) among SRMs of randomized controlled trials. CONCLUSION: This umbrella review of systematic review and meta-analysis found that prenatal folic acid and/or multivitamin supplementation was associated with a 57% reduction in NTD. Participants who took folic acid supplementation were associated with a slightly higher (77%) percentage of reduction in NTD compared with those who took multivitamin (37%). Reductions of 80% and 50% were observed for reoccurrence and occurrence prevention of NTD. Reductions of 57% and 55% of NTD have been found in SRM of RCTs and observational studies. This umbrella review revealed that both folic acid and multivitamin were associated with significantly lower levels of NTD in children. Considering the incorporation of those supplements in NTD prevention strategies during the preconception period is recommended. More large-scale prospective cohort and RCTs are needed to understand the protective effect of multivitamins and/or folic acid on NTD risk addressing the molecular mechanisms and to determine the optimal dose, duration, and timing of maternal multivitamin and folic acid intake for best child NTD risk reduction.

Maternal Smoking during Pregnancy and its effects on Neural Tube Defects.

Objectives: Maternal smoking is a potent teratogen among congenital malformations, however its role in the development of Neural Tube Defects (NTDs) is still unclear. In this systematic review, we intend to further investigate the interaction of smoking during pregnancy and the incidence of NTDs. Materials & Methods: This article was written according to PRISMA criteria from February 2015 and August 2022. After examining the four stages of PRISMA criteria, we selected clinical articles. These articles were selected from PubMed, Scopus and Google scholar (for results follow-up) databases. We gathered NTDs effect and types, smoking type and habit of parents, from neonates. Results: Eventually, 8 articles were included by two separated authors, Smoking was associated with an increase NTDs in the population of pregnant mothers and also among children whose fathers smoked. The main side effects that were considered to be the cause of NTDs besides smoking were alcohol and BMI (18.5-24.9). Smoking also affects the level of folic acid as a substance with an essential role that affects the closure of the neural tube. folic acid available to infants changing along with the level of other blood elements such as zinc, that necessary prevent for NTDs condition. Conclusion: Parental smoking can be considered as one of the strong teratogens in the occurrence of NTDs. Smoking, whether active or passive by the mother, or by the father, is associated with the occurrence of NTDs, In order to reduce the prevalence this disorder, we advise pregnant mothers and neonate's fathers to quit smoking.

First-trimester ultrasound of the cerebral lateral ventricles in fetuses with open spina bifida: a retrospective cohort study.

BACKGROUND: Beyond 18 weeks of gestation, an increased size of the fetal lateral ventricles is reported in most fetuses with open spina bifida. In the first trimester of pregnancy, the definition of ventriculomegaly is based on the ratio of the size of the choroid plexus to the size of the ventricular space or the entire fetal head. However, contrary to what is observed from the midtrimester of pregnancy, in most fetuses with open spina bifida at 11 to 13 weeks of gestation, the amount of fluid in the ventricular system seems to be reduced rather than increased. OBJECTIVE: This study aimed to compare the biometry of the lateral ventricles at 11 0/7 to 13 6/7 weeks of gestation between normal fetuses and those with confirmed open spina bifida. STUDY DESIGN: This was a retrospective cohort study that included all cases of isolated open spina bifida detected at 11 0/7 to 13 6/7 weeks of gestation over a period of 5 years and a group of structurally normal fetuses attending at our center over a period of 1 year for the aneuploidy screening as controls. Transventricular axial views of the fetal brain obtained from cases and controls were extracted from the archive for post hoc measurement of cerebral ventricles. The choroid plexus-to-lateral ventricle length ratio, sum of the choroid plexus-to-lateral ventricle area ratio, choroid plexus area-to-fetal head area ratio, and mean choroid plexus length-to-occipitofrontal diameter ratio were calculated for both groups. The measurements obtained from the 2 groups were compared, and the association between each parameter and open spina bifida was investigated. RESULTS: A total of 10 fetuses with open spina bifida were compared with 358 controls. Compared with controls, fetuses with open spina bifida showed a significantly smaller size of the cerebral ventricle measurements, as expressed by larger values of choroid plexus-to-lateral ventricle area ratio (0.49 vs 0.72, respectively; P<.001), choroid plexus-to-lateral ventricle length ratio (0.70 vs 0.79, respectively; P<.001), choroid plexus area-to-fetal head area ratio (0.28 vs 0.33, respectively; P=.006), and choroid plexus length-to-occipitofrontal diameter ratio (0.52 vs 0.60, respectively; P<.001). The choroid plexus-to-lateral ventricle area ratio was found to be the most accurate predictor of open spina bifida, with an area under the curve of 0.88, a sensitivity of 90%, and a specificity of 82%. CONCLUSION: At 11 0/7 to 13 6/7 weeks of gestation, open spina bifida is consistently associated with a reduced amount of fluid in the lateral cerebral ventricles of the fetus, as expressed by a significantly increased choroid plexus-to-lateral ventricle length ratio, choroid plexus-to-lateral ventricle area ratio, choroid plexus area-to-fetal head area ratio, and choroid plexus length-to-occipitofrontal diameter ratio.

Characteristics and Outcomes of Patients With Spina Bifida in Texas by Patient Age.

INTRODUCTION: Spina bifida (SB) occurs in 3.5/10,000 live births and is associated with significant long-term neurologic and urologic morbidity. We explored the characteristics and outcomes of pediatric patients with SB and the facilities that treat them in Texas. METHODS: We retrospectively reviewed a statewide hospital inpatient discharge database (2013-2021) to identify patients aged <18 y with SB using International Classification of Diseases 9/10 codes. Patients transferred to outside hospitals were excluded to avoid double-counting. Descriptive statistics and chi-square test were performed. RESULTS: Seven thousand five hundred thirty one inpatient hospitalizations with SB were analyzed. Most SB care is provided by a few facilities. Two facilities (1%) averaged >100 SB admissions per year (33% of patients), while 15 facilities (8%) treat 10-100 patients per year (51% of patients). Most facilities (145/193, 75%) average less than one patient per year. Infants tended to be sicker (17% extreme illness severity, P < 0.001). Overall mortality is low (1%), primarily occurring in the neonatal period (8%, P < 0.001). Most admissions are associated with surgical intervention, with 63% of encounters having operating room charges with an average cost of $25,786 ± 24,884. Admissions for spinal procedures were more common among infants, whereas admissions for genitourinary procedures were more common among older patients (P < 0.001). The average length of stay was 8 ± 16 d with infants having the longest length of stay (19 ± 33, P < 0.001). CONCLUSIONS: Patients have significant long-term health needs with evolving pediatric surgical indications as they grow. Pediatric SB care is primarily provided by a small number of facilities in Texas. Longitudinal care coordination of their multidisciplinary surgical care is needed to optimize patient care.

Pin1 Downregulation Is Involved in Excess Retinoic Acid-Induced Failure of Neural Tube Closure.

Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans isomerase 1 (Pin1) is a prolyl isomerase that uniquely regulates cell signaling by manipulating protein conformation following phosphorylation, although its involvement in neuronal development remains unknown. In this study, we explored the involvement of Pin1 in NTDs and its potential mechanisms both in vitro and in vivo. The levels of Pin1 expression were reduced in NTD models induced by all-trans retinoic acid (Atra). Pin1 plays a significant role in regulating the apoptosis, proliferation, differentiation, and migration of neurons. Moreover, Pin1 knockdown significantly was found to exacerbate oxidative stress (OS) and endoplasmic reticulum stress (ERs) in neuronal cells. Further studies showed that the Notch1-Nrf2 signaling pathway may participate in Pin1 regulation of NTDs, as evidenced by the inhibition and overexpression of the Notch1-Nrf2 pathway. In addition, immunofluorescence (IF), co-immunoprecipitation (Co-IP), and GST pull-down experiments also showed that Pin1 interacts directly with Notch1 and Nrf2. Thus, our study suggested that the knocking down of Pin1 promotes NTD progression by inhibiting the activation of the Notch1-Nrf2 signaling pathway, and it is possible that this effect is achieved by disrupting the interaction of Pin1 with Notch1 and Nrf2, affecting their proteostasis. Our research identified that the regulation of Pin1 by retinoic acid (RA) and its involvement in the development of NTDs through the Notch1-Nrf2 axis could enhance our comprehension of the mechanism behind RA-induced brain abnormalities.

Complex neural tube and skeletal malformations, resembling Chiari malformations, in two calves.

Two 1-day-old full-term female calves from different farms located in the Brazilian state of Rio Grande do Sul were unable to stand due to paresis of the pelvic limbs. Both calves had spina bifida on the spinal lumbar segment and were submitted to euthanasia due to poor prognosis. Postmortem examination revealed cerebellar herniation, caudal displacement of the brainstem, rostral deviation of the cranial nerves, caudal extension of occipital lobes, absence of dorsal lamina of lumbar vertebrae with exposed spinal cord, myelodysplasia, kyphosis, segmental spinal agenesis, renal fusion, muscular atrophy, and arthrogryposis. Histology highlighted myelodysplasia (syringomyelia and diplomyelia) and muscular atrophy. The reverse transcription-polymerase chain reactions for ruminant pestivirus were negative. Based on these lesions, the diagnosis of complex neural tube and skeletal malformations was made. A review of previous publications on calves diagnosed with these malformations, originally called Chiari or Arnold-Chiari malformations, revealed a wide range of nervous system and skeletal lesions. These variations amplified the uncertainty regarding whether all cases represent the same disorder and reinforced the importance of reconfiguring the terminology.

Anencephaly in a triplet pregnancy: Unprecedented spontaneous reabsorption in-utero and subsequent normal delivery via c-section: A rare case report.

Multiple pregnancies are infrequently encountered, with the incidence of spontaneous triplet pregnancies estimated at approximately 1 in 7000 pregnancies. Triplet gestations are recognized for their propensity to bring about a spectrum of pregnancy related complexities, encompassing fetal structural abnormalities, neurological anomalies, disturbances in amniotic fluid levels, preterm labor, and suboptimal neonatal outcomes. Anencephaly is a serious congenital defect where the brain and skull do not fully develop, often leading to a poor prognosis. It's a preventable neural tube defect (NTD) with timely intake of folic acid, is caused by the incomplete closure of the neural tube during fetal development, resulting in the absence of the cerebrum (responsible for thinking and coordination) and the front part of the brain (forebrain) in affected infants. While anencephaly in a triplet is scarcely reported, spontaneous reabsorption of an anencephalic fetus in utero is a rare and unexpected event, with no documented cases in triplet pregnancies until now. We report a case of anencephaly in a triplet pregnancy where the mother presented late during her third trimester, the reabsorption of the anencephalic fetus in utero is an unprecedented event, highlighting the unique nature of this triplet pregnancy.

Prenatal diagnosis of meningomyelocele resolves as a mature cystic teratoma in the thoracolumbar region.

A mature cystic teratoma is a mass with heterogeneous appearance, consisting of adult tissue with two or three layers: endoderm, mesoderm, and ectoderm. It is a rare, benign transformation of somatic tissue most commonly found in the sacrococcygeal region and may resemble an uncomplicated spina bifida on prenatal ultrasonography. In this case report, we describe a female newborn with an extremely rare mature cystic teratoma in the thoracolumbar region. She presented prenatally with a preliminary diagnosis of meningomyelocele, diastematomyelia, and Chiari II malformation and a possible teratoma. However, a mass containing solid glandular tissues and bony calcifications approximately 3 × 4 cm in size was observed in the thoracolumbar region upon birth. During surgical resection, no nerve roots were found in the associated meningocele. The patient retained full lower body function postoperatively following surgical excision of the thecal sac and teratoma.

Surgical outcomes of myelomeningocele repair: A 20-year experience from a single center in a middle-income country.

BACKGROUND AND PURPOSE: Spina bifida is the second major cause of congenital disorders and the most common central nervous system congenital malformation compatible with life primarily. Herein, we describe the short-term outcome of post-natal Myelomeningocele (MMC) surgical management and predictors of its postoperative complications and mortality. METHODS: This retrospective chart review studies the children who underwent post-natal surgical management for MMC in Namazi hospital, a tertiary referral center, in southern Iran from May 2001 to September 2020. RESULTS: 248 patients were included in this study. The mean age at the operation was 8.47 ± 8.69 days. The most common site of involvement of MMC was Lumbosacral (86%, n = 204). At the evaluation conducted prior to the operation, cerebrospinal fluid leak was observed in 7% (n=16) of the patients. Postoperatively, 5.7% of the patients expired in the 30-day follow-up after the operation (n = 14), while 24% needed readmission (n = 47). The most common complications leading to readmission were wound dehiscence (n = 10, 42%) and wound purulence (n = 6, 25%). Only the site of the lesion (p-value = 0.035) was associated with postoperative complication. After controlling for potential confounders, the site of the lesion (adjusted odds ratio = 0.146, 95% confidence interval = 0.035-0.610, p-value = 0.008) and age at surgery (adjusted odds ratio = 1.048, 95% confidence interval = 1.002-1.096, p-value = 0.041) were significantly associated with mortality CONCLUSIONS: The age of the patients at the surgery and the site of the lesion are the two factors that were associated with mortality. However, further investigations into preoperative interventions and risk factors to mitigate the risk of complications and mortality are highly encouraged.