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.

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.

Planar Cell Polarity Signaling: Coordinated Crosstalk for Cell Orientation.

The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. The PCP system uses inter- and intracellular feedback interactions between components of the core PCP, characterized by coordinated planar polarization and asymmetric distribution of cell populations inside the cells. PCP signaling connects the anterior-posterior to left-right embryonic plane polarity through the polarization of cilia in the Kupffer's vesicle/node in vertebrates. Experimental investigations on various genetic ablation-based models demonstrated the functions of PCP in planar polarization and associated genetic disorders. This review paper aims to provide a comprehensive overview of PCP signaling history, core components of the PCP signaling pathway, molecular mechanisms underlying PCP signaling, interactions with other signaling pathways, and the role of PCP in organ and embryonic development. Moreover, we will delve into the negative feedback regulation of PCP to maintain polarity, human genetic disorders associated with PCP defects, as well as challenges associated with PCP.

Human diprosopus: Case report of a rare congenital abnormality.

Diprosopus is a congenital anomaly in which partial or complete duplication of craniofacial structures occurs. Because it is rare, the mortality rate is high, and information concerning this anomaly is scarce. This study describes a case of human diprosopus in a 9-year-old male individual, who has severe complications associated with the central nervous, cardiovascular, respiratory, and digestive systems. Since birth, he has been monitored in a specialized hospital environment, where he has undergone several surgeries and multidisciplinary treatments. Regarding the craniofacial aspects, he had agenesis of the corpus callosum, floor of the nasal cavity, and floor of the anterior cranial fossa, in addition to the presence of bone dysplasia, ocular hypertelorism and cleft palate with nasal and oral teratoma. Regarding dental characteristics, the patient has duplication of the maxilla, mandible, tongue, and some teeth. After complementary imaging exams, several supernumerary teeth were found, with some being impacted and in complex regions, with an indication for extraction due to the risks of impaction, irruptive deviation, root resorption, and associated cystic or tumoral lesions. Because of the numerous complications, knowledge, and preparation of the entire team is necessary for the correct management of the case.

Neural tube defects and epigenetics: role of histone post-translational histone modifications.

Neural tube defects (NTDs) are the most common congenital anomalies of the CNS. It is widely appreciated that both genetic and environmental factors contribute to their etiology. The inability to ascribe clear genetic patterns of inheritance to various NTD phenotypes suggests it is possible that epigenetic mechanisms are involved in the etiology of NTDs. In this context, the contribution of DNA methylation as an underlying contributing factor to the etiology of NTDs has been extensively reviewed. Here, an updated accounting of the evidence linking post-translational histone modifications to these birth defects, relying heavily upon studies in humans, and the possible molecular implications inferred from reports based on cellular and animal models, are presented.

Multidisciplinary management of people with spina bifida across the lifespan.

The average worldwide prevalence of neural tube defects (NTDs) is 1.0 per 1000 births. Its development is multifactorial due to genetic and non-genetic factors. Spina bifida (SB) is one of main representatives of NTD. The spinal cord lesion level is the main determinant of the level of paralysis, numbness, and difficulties with bladder/bowel functions. Myelomeningocele prenatal repair reduces hydrocephalus and hindbrain herniation and improves motor function. The severity of hydrocephalus is associated with poorer neurodevelopmental outcomes whether operated on prenatally or after birth. People with SB tend to have a lower IQ and cognitive difficulties. Early diagnosis, proactivity, and lifelong multidisciplinary follow-up are key protective issues. Invasive urological interventions should be considered in selected patients after failure of conservative treatment. Transition to adult care should be well planned as it is challenging. Health literacy is directly associated with success at transition. Sexuality and fertility should be addressed before/during puberty. Overall, the rates of fecal and urinary continence and skin breakdown increase with age, whereas the ability to ambulate declines with age. Bowel and urinary incontinence are independent predictors of lower health-related quality of life (HRQoL) in adults with SB. Bowel incontinence has negative impact on HRQoL regardless of frequency or amount. Long-term caregiver support should be offered at diagnosis. Survival at a mean of 50 years is poor, at 32%, due to central nervous system deaths, cancer, urological disease, and sepsis. Challenges to implementation of recommended practices exist, especially in low and middle-income countries.

"Prevalence and secular trend of neural tube defects in fetal deaths in Argentina, 1994-2019".

BACKGROUND: Fetal deaths are a major source of information on the epidemiology of neural tube defects (NTDs; anencephaly and myelomeningocele). We analyzed NTDs prevalence and secular trend using fetal death records between 1994 and 2019 in Argentina. MATERIALS AND METHODS: Data were obtained from the Department of Statistics and Information of the Ministry of Health (DEIS). Using the number of fetal deaths due to anencephaly and myelomeningocele, we estimated the proportion of all fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) during pre- and post-fortification period in Argentina. We also estimated the ratio of fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) to 10,000 live births. Secular trend in the outcomes was analyzed using a Poisson model and Joinpoint regression analysis. RESULTS: In the entire period analyzed, the NTD proportion on fetal deaths was 1.32. In 1994, NTDs accounted for 34.7% of congenital malformations fetal deaths (CM) and 1.7% of all fetal deaths, whereas in 2019, these percentages were 9.4% and 0.5%, respectively. NTDs present a negative secular trend (p < .05). The risk of fetal death due to anencephaly and myelomeningocele decreases between 2005 and 2019 by 67% and 51% respectively (p < .05) in comparison to the period between 1994 and 2004 before the effective fortification of wheat flour used in the food industry destined for the domestic market. DISCUSSION AND CONCLUSION: We found a significant decrease in the risk of all fetal deaths due to NTDs, particularly anencephaly, in Argentina over the study period, with most reduction observed during the mandatory flour fortification era (introduced in Argentina in 2002). The inclusion of fetal deaths in NTD surveillance, coupled or uncoupled with other pregnancy outcomes, is essential for monitoring preventive supplementation measures.

Prevalencia de defectos congénitos folato-sensibles en la provincia de Villa Clara / Prevalence of folate-sensitive birth defects in Villa Clara province

Introducción: Los defectos congénitos son un problema global que anualmente afecta a 7,9 millones de recién nacidos, los cuales constituyen la primera causa de muerte en los países desarrollados, y la segunda en países en vías de desarrollo, como es el caso de Cuba. Objetivos: Determinar la prevalencia de defectos congénitos folato-sensibles entre nacidos vivos, nacidos muertos e interrupciones electivas del embarazo. Métodos: Se realizó un estudio descriptivo y transversal en la provincia de Villa Clara donde se incluyeron todos los casos con defectos congénitos folato-sensibles diagnosticados entre 2013 y 2018. Resultados: Las cardiopatías congénitas conotruncales, el síndrome Down y los defectos del tubo neural fueron los fenotipos clínicos más prevalentes. La tasa de prevalencia ajustada fue de 5,79 por 1 000 nacimientos. Se constató una mayor tasa de prevalencia entre nacidos muertos y se interrumpió el 43,26 % de los embarazos con defectos diagnosticados prenatalmente. Las mayores tasas de prevalencia ajustada de cardiopatías y hendiduras labiopalatinas se identificaron en los municipios de Corralillo y Quemado de Güines, mientras que Placetas tuvo las mayores tasas de defectos del tubo neural y síndrome Down, y Manicaragua las de gastrosquisis. Conclusiones: La mayor frecuencia de defectos congénitos entre nacidos muertos puede estar en relación con la gran expresividad variable de los defectos estudiados, donde se incluyen fenotipos clínicos de gravedad. En los diferentes municipios con elevadas tasas de prevalencia de estos defectos están involucrados diferentes factores de riesgo ambientales que actúan sobre un genotipo que predispone a estos defectos congénitos.

Introduction: congenital defects are a global problem, annually affecting 7.9 million newborns. They constitute the leading cause of death in developed countries and the second one in developing countries like Cuba. Objective: to determine the prevalence of folate-sensitive birth defects among live births, stillbirths and elective pregnancy terminations. Methods: a descriptive and cross-sectional study was carried out in Villa Clara province, where all cases with folate-sensitive birth defects diagnosed between 2013 and 2018 were included. Results: conotruncal congenital heart diseases, Down syndrome and neural tube defects were the most prevalent clinical phenotypes. The adjusted prevalence rate was 5.79 per 1,000 births. A higher prevalence rate was found among stillbirths and 43.26% of pregnancies with prenatally diagnosed defects were terminated. The highest rates of adjusted prevalence of cleft lip and palate and heart diseases were identified in Corralillo and Quemado de Güines municipalities, while Placetas had the highest rates of neural tube defects and Down syndrome, as well as Manicaragua those of gastroschisis. Conclusions: the higher frequency of congenital defects among stillbirths may be related to a highly variable expressivity of the studied defects, where serious clinical phenotypes are included. Different environmental risk factors acting on a genotype that predisposes these congenital defects are involved in the different municipalities with high prevalence rates of these defects.

Síndrome de Currarino incompleto. Presentación de un caso

El síndrome de Currarino es una enfermedad hereditaria y de baja incidencia, compuesta por una tríada: estenosis anal, malformación sacro coccígea y masa presacra. Puede cursar desapercibido hasta la adultez y generar subdiagnósticos. Se describe un paciente de 75 años, masculino, piel negra, de procedencia urbana y con antecedentes de hipertensión arterial, quien acudió al hospital por presentar hematuria, dolor en fosa lumbar izquierda y estreñimiento. Se realizaron estudios imagenológicos, como ultrasonido, tomografía de abdomen y resonancia magnética lumbosacra, los cuales condujeron al diagnóstico de tumor renal, síndrome de Currarino incompleto (dado por dos elementos de la triada: malformación sacro coccígea y masa presacra) asociado a otra enfermedad malformativa raquimedular, médula anclada. Son pocos los casos reportados en el mundo (casi 300), por lo que se considera una entidad rara, pero de fácil diagnóstico debido al advenimiento de las nuevas tecnologías en el campo de la imagenología.

Currarino syndrome is a hereditary disease with a low incidence, composed of a triad: anal stenosis, sacrococcygeal malformation and presacral mass. It can go unnoticed until adulthood and generate subdiagnoses. A 75-years-old male, black-skinned, urban origin patient with a history of arterial hypertension is described, who attended the hospital presenting hematuria, pain in the left lumbar fossa, and constipation. Radiological studies such as ultrasound, abdominal tomography and lumbosacral magnetic resonance were performed, which led to the diagnosis of a renal tumor, incomplete Currarino syndrome (given by two elements of the triad: sacrococcygeal malformation and presacral mass) associated with another spinal cord malformation disease, tethered cord. There are few cases reported in the world (almost 300), so it is considered a rare entity, but easy to diagnose due to new imaging technologies.

A quest for genetic causes underlying signaling pathways associated with neural tube defects.

Neural tube defects (NTDs) are serious congenital deformities of the nervous system that occur owing to the failure of normal neural tube closures. Genetic and non-genetic factors contribute to the etiology of neural tube defects in humans, indicating the role of gene-gene and gene-environment interaction in the occurrence and recurrence risk of neural tube defects. Several lines of genetic studies on humans and animals demonstrated the role of aberrant genes in the developmental risk of neural tube defects and also provided an understanding of the cellular and morphological programs that occur during embryonic development. Other studies observed the effects of folate and supplementation of folic acid on neural tube defects. Hence, here we review what is known to date regarding altered genes associated with specific signaling pathways resulting in NTDs, as well as highlight the role of various genetic, and non-genetic factors and their interactions that contribute to NTDs. Additionally, we also shine a light on the role of folate and cell adhesion molecules (CAMs) in neural tube defects.

Conocimientos sobre el ácido fólico periconcepcional en mujeres puérperas del hospital de la mujer, La Paz-Bolivia / Awareness of periconceptional folic acid in postpartum women at the hospital de la mujer, La Paz-Bolivia

INTRODUCCIÓN Y/O ANTECEDENTES: Los defectos del tubo neural se encuentran entre las anomalías congénitas más comunes en todo el mundo, el ácido fólico (0.4-0.8 ug/día) reduce el riesgo de ocurrencia y recurrencia, por lo que se recomienda su uso concepcional y periconcepcional. El conocimiento de sus efectos protectores varía mucho en la población. OBJETIVOS: Describir el conocimiento de las puérperas sobre el uso correcto del ácido fólico y sus alcances como factor protector. MATERIAL Y MÉTODO: Se condujeron encuestas entre un grupo de mujeres puérperas del Hospital de la Mujer mediante cuestionarios estructurados para obtener información el conocimiento del uso del ácido fólico periconcepcional. RESULTADOS: Entrevistamos 87 puérperas. El conocimiento y el uso del ácido fólico entre las entrevistadas fue bajo, 51% y 48.3% respectivamente. La escolaridad en este grupo poblacional es un factor predictivo del conocimiento y uso correcto del ácido fólico. DISCUSIÓN, CONCLUSIONES Y RECOMENDACIONES: El conocimiento del ácido fólico es relativamente bajo entre las mujeres puérperas entrevistadas, su uso durante el embarazo es insuficiente y la suplementación con antes de la concepción es nula. Aún nos queda un largo camino por recorrer. Se recomienda promover el conocimiento y el uso del ácido fólico en etapa periconcepcional, así como mayor información sobre los alimentos fortificados.

INTRODUCTION AND BACKGROUND: Neural tube defects are among the most common congenital anomalies worldwide; folic acid reduces their risk of occurrence and is strongly recommended for conceptional and periconceptional use. Awareness of its protective effects varies widely among populations. OBJECTIVES: To measure the awareness of postpartum women about the correct use of folic acid and its protectants. MATERIALS AND METHODS: A survey was conducted in one group of postpartum women using structured questionnaires to obtain information on awareness and use of folic acid. RESULTS: We interviewed 87 postpartum women. Awareness and use of folic among the interviewees were low, 51% and 48.3% respectively. Schooling is a predictor of folic acid correct use and awareness. DISCUSSION, CONCLUSIONS, AND RECOMMENDATIONS: Awareness of folic acid is relatively low among pregnant Bolivian women, its use during pregnancy is insufficient and supplementation before conception is zero. We still have a long way to go. We recommend the promotion of awareness and the use of folic acid in pregnant women.

Barriers and facilitators to the implementation of mandatory folate fortification as an evidence-based policy to prevent neural tube defects.

BACKGROUND: Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities. AIM: This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide. METHODS: A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy. RESULTS: We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively. CONCLUSIONS: Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.

Pre and postnatal care characteristics and management features of children born with myelomeningocele in the post-folate fortification era of staple foods in Costa Rica (2004-2022).

PURPOSE: To describe the clinical characteristics of pre- and postnatal care of children born with myelomeningocele in Costa Rica from 2004 to 2022 after the introduction of mandatory fortification of four major staple foods, describing the clinical features of this cohort including the size of the meningomyelocele, neurological level, presence of symptomatic Chiari II at birth, kyphosis, and the severity of hydrocephalus requiring cerebrospinal fluid (CSF) shunting. These results were compared against the pre-fortification historical data to determine favorable outcomes from this health policy. METHODS: We performed a retrospective review of the clinical records of patients with myelomeningocele at the spina bifida clinic from the National Children's Hospital of Costa Rica who were born between 2004 and 2022, a period when staple food fortification was implemented in the country for four food staples (wheat and corn flour, rice, and dairy products). Pre and postnatal care data pertaining to the number of obstetric ultrasound studies, the trimester in which they were performed, the detection of myelomeningocele and associated hydrocephalus, gestational age and route of delivery, neurological level, myelomeningocele defect size, associated kyphosis and symptomatic Chiari II malformation at birth, time periods of myelomeningocele repair, and CSF shunting were examined. A descriptive comparative frequency analysis between myelomeningocele (MMC) defect size, CSF shunt insertion, symptomatic Chiari II, and kyphosis between the different functional levels was performed with the estimation of the Fisher's exact chi-square test by contingency tables, and 0.05 was set as significance level. Additionally, the postnatal features of this cohort were compared against pre-fortification historical data obtained from 100 live-born patients between 1995 and 1996. RESULTS: A total of 215 patients that were live born between 2004 and 2022 were eligible for analysis with a follow up ranging from 1 to 19 years (median follow up: 7.9 years). Among 99.1% of the mothers of patients who had prenatal consultations, 95.8% had an average of 3.8 obstetric ultrasound studies which led to a 59% prenatal detection rate of myelomeningocele. The pre and post fortification features showed a male/female ratio that changed from 0.92 to 1.25 respectively. Among these newborns, there was an increase from 54 to 64% cesarean sections as method for delivery. Only 26% of the pre fortification patients had the MMC defect repaired in the first 24 h, 32% from 24 to 72 h, 20% from 72 h to 1 week, and 22% later than 10 days respectively which deeply contrasted with the post fortification cohort where 7.5% had the MMC defect repaired in less than 8 h, 12.2% from 8 to 12 h, 66.5% 12-24 h, and 12.7% from 24 to 48 h and 1% later than 48 h, respectively (P < 0.01). Regarding the post fortification myelomeningocele anatomic and functional characteristics, defect size was measured as less than 3 cm in 7% of cases, 3 to 5 cm in 50% of cases, 5 to 7 cm in 42% of cases, and greater than 7 cm in 1% of cases. Thirteen percent of the cases had paraplegia due to a thoracic level, 10% had a high lumbar level, 58% had a middle lumbar level, 13% a lower lumbar level, and 6% only sacral compromise. When the data from the pre and post fortification cohorts were adjusted and compared, there was a reduction from thoracic/high lumbar cases from 26 to 23% (P < 0.56), with an increase of middle lumbar cases from 43 to 58% and a reduction from 25 to 13% of low lumbar cases (P < 0.01) while there was no change in the 6% percentage of sacral cases respectively. Lesions that were considered too extensive or larger than 7 cm decreased from 7 to 1% while associated kyphotic deformities decreased from 6 to 1.4% (P < 0.01); symptomatic Chiari II malformation at birth also decreased from 7 to 2% in the pre- and post-fortification cohorts respectively with all these changes being statistically significant (P < 0.01). Seventy-nine percent and 80% of the pre and post FAF cohorts required CSF VP shunting with a mean time for insertion of 10 days after spinal defect closure with no significant statistical change between the two groups. CONCLUSIONS: This study describes a four-staple folate fortified population of live-born patients with myelomeningocele lesions whose neurological level, defect size, and associated deformities such as spinal kyphosis and symptomatic Chiari II at birth suggest that folate fortification could have diminished the severity of this congenital disease.

Neural tube defects: Prevalence, mortality, and maternal characteristics in two departmental hospitals in the northwestern region of Nicaragua, 2006-2018.

BACKGROUND: Congenital anomalies are the fifth most common cause of neonatal mortality in Nicaragua, and neural tube defects (NTDs) are the most common of all cases of lethality associated with a birth defect. Prevalence and mortality estimates are needed to propose effective intervention strategies that prevent NTDs over time. METHODS: A cross-sectional study was carried out in northwestern Nicaragua from January 2006 to December 2018. All cases of NTDs (anencephaly, spina bifida, and encephalocele) were registered in hospital surveillance systems, and the medical histories of the mothers and newborns were reviewed. Prevalence was calculated by considering the number of live births and stillbirths older than 20 weeks of gestation with NTDs, divided by the total number of live births and stillbirths in each study year. Neonatal mortality rate (NMR) for NTD, and case fatality for spina bifida was calculated. RESULTS: Two hundred fifty cases of NTDs were identified from 178,498 deliveries (177,316 live births and 1,182 stillbirths). The prevalence of NTDs during this time period was 14.01 (95% CI: 12.27-15.74) per 10,000 births. The prevalence of spina bifida (n = 140), anencephaly (n = 97), and encephalocele (n = 13) was 7.84, (95% CI: 6.54-9.14), 5.43 (95% CI: 4.30-6.45), and 0.73 (95% CI: 0.33-1.12) per 10,000 births, respectively. Mothers with fetus or newborns affected with NTDs did not use folic acid prior to conception, and 11% experienced periods of hyperthermia during the first trimester of pregnancy. NMR for NTDs was 0.55 per 1.000 livebirths. Case fatality for all NTDs and for spina bifida were 55% and 18%, respectively. CONCLUSION: The prevalence and mortality of NTDs in the northwestern region of Nicaragua present peaks and troughs during the study period. Spina bifida was the most frequent type of NTD. We believe that these findings could be of use by health policy makers to strengthen the primary prevention of NTDs in the region through the monitoring of the food fortification policy and folic acid supplementation to women of childbearing age. Additional etiologic studies of NTDs should be considered to identify additional prevention measures.

The role of Wnt signaling in Xenopus neural induction.

Development of the central nervous system in amphibians has called attention from scientists for over a century. Interested in the matter of embryonic inductions, Hans Spemann and Hilde Mangold found out that the dorsal blastopore lip of the salamander's embryo has organizer properties. Such an ectopic graft could induce structures in the host embryo, including a neural tube overlying the notochord of a perfect secondary body axis. A couple of decades later, the frog Xenopus laevis emerged as an excellent embryological experimental model and seminal concepts involving embryonic inductions began to be revealed. The so-called primary induction is, in fact, a composition of signaling and inductive events that are triggered as soon as fertilization takes place. In this regard, since early 1990s an intricate network of signaling pathways has been built. The Wnt pathway, which began to be uncovered in cancer biology studies, is crucial during the establishment of two signaling centers in Xenopus embryogenesis: Nieuwkoop center and the blastula chordin noggin expression center (BCNE). Here we will discuss the historical events that led to the discovery of those centers, as well as the molecular mechanisms by which they operate. This chapter highlights the cooperation of both signaling centers with potential to be further explored in the future. We aim to address the essential morphological transformation during gastrulation and neurulation as well as the role of Wnt signaling in patterning the organizer and the neural plate.

Training model for the fetal myelomeningocele correction with multiportal endoscopic technique.

PURPOSE: The recent history of myelomeningocele has shown that treatment during the fetal life may reduce the risk of developing hydrocephalus in individuals by approximately 50%. Thus, a significant advancement involves fetal surgery performed through an endoscopic technique in which portals are placed to introduce the forceps and laparoscopic instruments. However, the development of this technique requires training; therefore, this study aimed to develop a training model for fetal myelomeningocele repair technique with multi-portal endoscopy. METHODS: Two stages of endoscopic technique development were performed. The first stage consisted of exercises in order to familiarize the surgeon with 2D-vision endoscopic surgery, associated with the application of exercises focused on surgical skills, such as the development of laparoscopic knots in a synthetic model. The second stage involved the creation and application of the stages of myelomeningocele closure with a non-living animal model consisting of a chicken breast to simulate the myelomeningocele and a basketball to simulate the gravid uterus, in which perforations were made to introduce vascular introducers (portals) that, as in vivo, are used as portals (trocars) for the introduction of laparoscopic instruments. Overall, two different scenarios with three portals and two portals were tested. RESULTS: In three-portal simulator, the triangular apex trocar was used for the introduction of 4-mm 0° or 30° optics or even Minop type neurodoscope (Aesculap®, Germany) that was operated by the assistant surgeon; the other two portals are used for the introduction of laparoscopic instruments. Thus, the surgeon is able to perform maneuvers bimanually since dissection to laparoscopic sutures. In two-portal simulator, the surgeon and assistant stay side by side and one of the portals is used for the optic and the other for the laparoscopic instruments. There is no possibility of bimanual dissection in this method. CONCLUSION: Realistic simulation models for endoscopic fetal surgery for myelomeningocele correction are easily performed and help develop the necessary skills for fetal surgery teams.

The First Case of Fetus in Fetu in Nicaragua: The Management Experience of the Pediatric Neurosurgery Team.

Fetus in fetu (FIF) is a rare congenital anomaly of asymmetric monozygotic twins, where the parasitic twin develops abnormally inside the body of the host twin. In most cases, it is incorporated into the sibling's abdomen, which frequently presents as a retroperitoneal mass. Currently, at least 200 cases have been reported worldwide, being this the first case in Nicaragua. We describe a case of a male newborn, born via cesarean section, with a history of multiple congenital malformations observed via ultrasound examination. At birth, a mass is observed on its dorsum that impresses a skull, but without the presence of bones, with three limbs, two upper and one lower, with an outline located transversely on the pelvic girdle and the presence of two male genitalia with agenesis of the testicles and an accessory kidney. A preoperative diagnosis of FIF and spinal dysraphism was made by computed tomography (CT) and magnetic resonance imaging (MRI). They shared a spinal cord and had the presence of an open spinal defect type meningocele with aberrant roots. After the diagnosis and discussion, the multidisciplinary team proceeded to surgery to perform the separation of the twin (FIF). The subsequent anatomopathological examination revealed that the fetus was anencephalic and had reliable FIF characteristics. The resection was performed followed by the closure of the 430 mL meningocele and complete separation of the spine and the parasitic twin. We present the first case of fetus in fetu in Nicaragua.

Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.

Integrated surveillance strategy to support the prevention of neural tube defects through food fortification with folic acid: the experience of Costa Rica.

PURPOSE: (1) To describe how Costa Rica implemented an integrated surveillance strategy of folate deficiency, neural tube defects (NTDs) prevalence, NTDs-associated infant mortality rate (NTDs-IMR), and folic acid food fortification (FAFF), to support with evidence NTDs prevention policies; (2) to disseminate updated data from monitoring programs. METHODS: We performed a cross-sectional analysis, using the databases of national surveillance systems for NTDs outcomes to compare NTDs-prevalence and NTDs-IMR observed in the pre-fortification (1987-1998) and post-fortification (2010-2020) periods. In addition, using data from FAFF monitoring program (2010-2020), means of folic acid concentration (mg/kg) and folic acid daily intake (µg/day) were calculated for each fortified food (corn and wheat flour, rice and milk), as well as its contribution to folic acid estimated average requirement (EAR). RESULTS: After FAFF Costa Rica showed a decrease of 84% in folic acid deficiency in women of childbearing age, as well as a 53% decrease in the prevalence of NTDs, falling from 11.82/10,000 to 5.52/10,000 livebirths. In addition, there was a 76% reduction in the NTDs-IMR from 77.01/100,000 to 18.66/100,000 livebirths. Between 2010 and 2020, all fortified foods provided an average contribution of 119% of the EAR of folic acid in the population. CONCLUSION: To reduce NTD risk, an integrated surveillance strategy is essential not only to base prevention strategies on evidence, but also to demonstrate their impact and improve interventions over time. The experience in Costa Rica provides evidence that this type of surveillance is feasible to be implemented in developing countries.

Defectos del tubo neural en recien nacidos en el hospital de la mujer / Neural tube defects in newborns in women's hospital

OBJETIVO: Conocer la prevalencia al nacimiento de los defectos del tubo neural en recién nacidos del Hospital de la Mujer, La Paz, Bolivia, período comprendido entre el año 2008 - 2017. DISEÑO METODOLÓGICO: Observacional, descriptivo, de corte transversal, retrospectivo. LUGAR: Hospital de la Mujer, a 3650 m.s.n.m. La Paz, Bolivia. MÉTODOS: Se examinaron los expedientes clínicos de todos los recién nacidos del Hospital de la Mujer, en período ya establecido. Para la detección de anomalías congénitas, se utilizaron libros de registro de nacimientos. Se ingresaron los datos a una base Excel, se procedió al análisis de los mismos a través del uso de la estadística descriptiva. RESULTADOS: Se recurrió a registros de 58120 expedientes de recién nacidos, se presentaron 1269 casos con Anomalías Congénitas (2.2%) con una prevalencia al Nacimiento (PN) de 21.83/10.000 RN (22.57/10.000 RN vivos). De dichos 1269 casos, 69 (5.44%) correspondieron a Defectos del Tubo Neural (DTN), con una PN de 11.87/10.000 RN (12.27/10.000 RN vivos), 59.42% DTN asociados al sexo masculino. El tipo de DTN más frecuente evidenciado fue Mielomeningocele (52.17%), y los DTN mortinatos representan el 17.39%. CONCLUSIONS: La llamativa diferencia encontrada, (en relación a la predilección por el sexo masculino), podría sugerir la presencia de una carga genética cuantitativamente mayor (propia de la población estudiada) en la etiología de los DTN en nuestro medio, ya que cuando las condiciones multifactoriales como los DTN afectan al sexo menos frecuentemente descrito, se puede asumir un peso mayor de los factores genéticos en relación a factores ambientales, siguiendo conceptos de heredabilidad y la teoría del umbral para este modo de herencia, sin embargo, somos conscientes que se requiere un tamaño de muestra mayor para arribar a conclusiones más certeras, dichos factores se adicionan al subregistro y posibles sesgos de registro evidenciados durante la realización del estudio.

OBJECTIVE: To know the prevalence at birth of neural tube defects in newborns at Hospital de La Mujer, La Paz, Bolivia, 3650 m.a.s.l, period between 2008 - 2017. PLACE: Women's Hospital, La Paz, Bolivia. METHODS: Observational, descriptive, cross-sectional, retrospective. The clinical records of all newborns were examined, in an already established period. For the detection of congenital anomalies, birth registration books were used. The data were entered into an Excel database, and analyzed through the use of descriptive statistics. RESULTS: 58120 newborn records were examined, 1269 cases with Congenital Anomalies (2.2%) with a prevalence at Birth (PB) of 21.83/10.000 RN (22.57/10.000 RN alive) were presented. Of these 1269 cases, 69 (5,44%) corresponded to Neural Tube Defects (NTD), with a PB of 11.87/10,000 RN (12.27/10,000 RN alive), 59.42% DTN associated with the male sex. The most frequent type of NTD evidenced was Myelomeningocele (52.17%), and stillborn DTNs represented 17.39%. CONCLUSIONS: The distinctive difference found (predilection of NTD for the male sex), could suggest the presence of a quantitatively greater genetic load (typical of the population studied) in the etiology of NTDs in our environment, since when multifactorial conditions affect the less frequently described sex, a greater weight of genetic factors can be assumed compared to environmental factors, following concepts of heritability and the threshold theory for this mode of inheritance; however, we are aware that a larger sample size is needed to arrive at more accurate conclusions, these factors are added to the underreporting and possible recording biases evidenced during the study.