Common Congenital Disabilities Research Articles

Risk factors associated with congenital central nervous system abnormalities in the National Hospital of Zinder, Niger

IntroductionCongenital malformations of the central nervous system (CNS) are morphological abnormalities of the brain and spinal cord that occur during fetal development. They constitute the second most common congenital disability, after congenital cardiac defects. Many risk factors have been identified; however, these studies included various types of congenital abnormality. Furthermore, there is a lack of information on risk factors for congenital CNS malformation, and notably in the Zinder region of Niger. ObjectiveThis study aimed to identify the risk factors associated with congenital CNS malformations in the Zinder region. MethodsIn a case-control design, patients with congenital CNS malformation were enrolled between June 2022 and April 2023 in the Department of Neurosurgery of the National Hospital of Zinder. ResultsFamily history of malformation (aOR:3.31, 95% CI:1.25−8.78) and consanguine marriage (aOR:2.28, 95% CI:1.23−4.20) were significantly associated with congenital CNS malformation. In contrast, folic acid supplementation (aOR:0.34, 95% CI:0.13, 0.89), multiparity (aOR:0.34, 95% CI:0.13, 0.89), and grand multiparity (aOR, 0.47; 95% CI:0.23, 0.97) had a protective effect. ConclusionRisk factors such as family malformation history and consanguine marriage increased the risk of developing congenital malformations of the central nervous system. In contrast, folic acid supplementation in the index period and multiparity had a significant protective effect.

SKGC: A General Semantic-level Knowledge Guided Classification Framework for Fetal Congenital Heart Disease.

Congenital heart disease (CHD) is the most common congenital disability affecting healthy development and growth, even resulting in pregnancy termination or fetal death. Recently, deep learning techniques have made remarkable progress to assist in diagnosing CHD. One very popular method is directly classifying fetal ultrasound images, recognized as abnormal and normal, which tends to focus more on global features and neglects semantic knowledge of anatomical structures. The other approach is segmentation-based diagnosis, which requires a large number of pixel-level annotation masks for training. However, the detailed pixel-level segmentation annotation is costly or even unavailable. Based on the above analysis, we propose SKGC, a universal framework to identify normal or abnormal four-chamber heart (4CH) images, guided by a few annotation masks, while improving accuracy remarkably. SKGC consists of a semantic-level knowledge extraction module (SKEM), a multi-knowledge fusion module (MFM), and a classification module (CM). SKEM is responsible for obtaining high-level semantic knowledge, serving as an abstract representation of the anatomical structures that obstetricians focus on. MFM is a lightweight but efficient module that fuses semantic-level knowledge with the original specific knowledge in ultrasound images. CM classifies the fused knowledge and can be replaced by any advanced classifier. Moreover, we design a new loss function that enhances the constraint between the foreground and background predictions, improving the quality of the semantic-level knowledge. Experimental results on the collected real-world NA-4CH and the publicly FEST datasets show that SKGC achieves impressive performance with the best accuracy of 99.68% and 95.40%, respectively. Notably, the accuracy improves from 74.68% to 88.14% using only 10 labeled masks.

Characteristics of hearing loss-associated gene mutations: A multi-center study of 119,606 neonates in Gannan.

HL is the second most common congenital disability in China, and its high incidence brings a serious burden of medical and educational sequelae. HL genetic screening enables the identification of individuals with inherited HL and carriers in a large scale. This study aimed to measure the detection rates of hearing loss (HL)-associated gene mutations in the Gannan population. The molecular etiology and risk factors of hereditary HL were also analyzed. In total, 119,606 newborns from 18 districts of Gannan were enrolled in this multi-center study conducted between April 2019 and April 2021. Otoacoustic Emission (OAE) was used for primary hearing screening 3 days after birth in quiet conditions, and OAE combined with automated auditory brainstem response (AABR) was applied 29-42 days after birth for those who failed or missed the initial screening. Meanwhile, high-throughput sequencing of hotspot HL-associated mutations in GJB2, GJB3, MTRNR1, and SLC26A4 were performed. Among the 119,606 newborns, 7796 (6.52%) failed the hearing screening. Genetic screening revealed that 5092 neonates (4.26%) carried HL-associated mutations. The detection rate of GJB2, SLC26A4, MTRNR1 and GJB3 mutations were 2.09%, 1.51%, 0.42% and 0.24%, respectively. The most prevalent variant was GJB2 c.235delC (1.74%). The second most prevalent variant was SLC26A4 c.919-2A>G (0.93%). The population who failed the hearing screening had a lower proportion (24.64%) of SLC26A4 gene variants compared to the population who passed (37.46%). Genetic screening identified 4612 (3.86%) carriers who were normal in hearing screenings. The concurrent hearing and genetic screening identified 480 (0.40%) neonates at high risk for hereditary HL. The results of this study suggest that the concurrent hearing screening and high-throughput genetic screening would greatly improve the effectiveness of newborn HL programs. This integration also facilitates the management of congenital HL, and aids in the prevention of aminoglycoside antibiotics-induced HL.

Prevalence of Breech Presentation and Other Gestational/Delivery Characteristics Among Patients Born With Developmental Dysplasia of the Hip.

Introduction Developmental dysplasia of the hip (DDH) is the most common congenital disability in newborns. The condition can range from a slight laxity in the hip joint to secondary femoral head injury, early osteoarthritis (OA), and mobility issues. There are several risk factors for DDH, including positive family history, female sex, breech presentation, and the presence of clubfoot. Early detection and treatment are crucial to avoidlong-term hip dysplasia and arthritis, which can cause difficulty in walking and discomfort. Breech presentation, in particular, is a significant risk factor for DDH, with spontaneous vaginal birth increasing the risk of hip pathology and instability compared to elective Caesarean section. However, whether breech presentation continues to be a risk factor for DDH in preterm children is unknown. Objective and methods This study aimed to investigate the prevalence of breech presentation and other gestational/delivery characteristics among newborns diagnosed with DDH.This retrospective study was conducted at Abha Maternity and Children Hospital,Abha, Saudi Arabia, over a period of six months. Data were collected from medical records of DDHcases diagnosed between 2016 and 2023. Data analysis was performed using Microsoft Excel (MicrosoftCorporation, Redmond, Washington, United States)and IBMSPSSStatistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). Descriptive statistics and statistical tests were used to analyze the data. Results Most of the diagnosed children were female (86.7%), and bilateral hip dislocation (40%) was the most common presentation. X-ray was the most common diagnostic tool (48.3%), and operative management was the most common management strategy (73.3%). A positive family history of DDH was reported in more than one-third of cases. The study also analyzed the association between complications during pregnancy and various factors such as mode of delivery, presentation at delivery, gestational age at delivery, and associated maternal diseases. The difference in complication rates between women who delivered via C-section and those who delivered vaginally was insignificant (p = 0.14). Similarly, the difference in complication rates between women with breech and cephalic presentation was not statistically significant (p = 0.094). The difference in complication rates between women who delivered preterm, at term, or post-term was also not statistically significant (p = 0.578). Furthermore, the association between complications during pregnancy and pregnancy-associated maternal diseases was not statistically significant (p = 1.00). Conclusion DDH is a significant health issue in newborns, leading to long-term mobility problems and discomfort. Positive family history of DDH is a significant risk factor. Breech presentation was not significantly associated with DDH in preterm children, and no significant associations were found between complications during pregnancy and various factors. Early detection and treatment of DDH are crucial for preventing long-term complications. Family history should be considered an important risk factor, emphasizing the need for screening programs in families with a history of DDH.

Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry

Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been made in understanding OFCs, due to advances in sequencing and genotyping technologies. Despite these advances, very little is known about the genetic interplay in the Malagasy population. Here, we performed high-resolution whole-exome sequencing (WES) on non-syndromic cleft lip with or without palate (nCL/P) trios in the Malagasy population (78 individuals from 26 families (trios)). To integrate the impact of genetic ancestry admixture, we computed both global and local ancestries. Participants demonstrated a high percentage of both African and Asian admixture. We identified damaging variants in primary cilium-mediated pathway genes WNT5B (one family), GPC4 (one family), co-occurrence in MSX1 (five families), WDR11 (one family), and tubulin stabilizer SEPTIN9 (one family). Furthermore, we identified an autosomal homozygous damaging variant in PHGDH (one family) gene that may impact metabiotic activity. Lastly, all variants were predicted to reside on local Asian genetic ancestry admixed alleles. Our results from examining the Malagasy genome provide limited support for the hypothesis that germline variants in primary cilia may be risk factors for nCL/P, and outline the importance of integrating local ancestry components better to understand the multi-ethnic impact on nCL/P.

Periderm Fate during Palatogenesis: TGF-β and Periderm Dedifferentiation

Failure of palatogenesis results in cleft palate, one of the most common congenital disabilities in humans. During the final phases of palatogenesis, the protective function of the peridermal cell layer must be eliminated for the medial edge epithelia to adhere properly, which is a prerequisite for the successful fusion of the secondary palate. However, a deeper understanding of the role and fate of the periderm in palatal adherence and fusion has been hampered due to a lack of appropriate periderm-specific genetic tools to examine this cell type in vivo. Here we used the cytokeratin-6A (Krt-6a) locus to develop both constitutive (Krt6ai-Cre) and inducible (Krt6ai-Cre ERT2 ) periderm-specific Cre driver mouse lines. These novel lines allowed us to achieve both the spatial and temporal control needed to dissect the periderm fate on a cellular resolution during palatogenesis. Our studies suggest that, already before the opposing palatal shelves contact each other, at least some palatal periderm cells start to gradually lose their squamous periderm-like phenotype and dedifferentiate into cuboidal cells, reminiscent of the basal epithelial cells seen in the palatal midline seam. Moreover, we show that transforming growth factor–β (TGF-β) signaling plays a critical periderm-specific role in palatogenesis. Thirty-three percent of embryos lacking a gene encoding the TGF-β type I receptor (Tgfbr1) in the periderm display a complete cleft of the secondary palate. Our subsequent experiments demonstrated that Tgfbr1-deficient periderm fails to undergo appropriate dedifferentiation. These studies define the periderm cell fate during palatogenesis and reveal a novel, critical role for TGF-β signaling in periderm dedifferentiation, which is a prerequisite for appropriate palatal epithelial adhesion and fusion.

Gene-Edited Human-Induced Pluripotent Stem Cell Lines to Elucidate DAND5 Function throughout Cardiac Differentiation.

(1) Background: The contribution of gene-specific variants for congenital heart disease, one of the most common congenital disabilities, is still far from our complete understanding. Here, we applied a disease model using human-induced pluripotent stem cells (hiPSCs) to evaluate the function of DAND5 on human cardiomyocyte (CM) differentiation and proliferation. (2) Methods: Taking advantage of our DAND5 patient-derived iPSC line, we used CRISPR-Cas9 gene-editing to generate a set of isogenic hiPSCs (DAND5-corrected and DAND5 full-mutant). The hiPSCs were differentiated into CMs, and RT-qPCR and immunofluorescence profiled the expression of cardiac markers. Cardiomyocyte proliferation was analysed by flow cytometry. Furthermore, we used a multi-electrode array (MEA) to study the functional electrophysiology of DAND5 hiPSC-CMs. (3) Results: The results indicated that hiPSC-CM proliferation is affected by DAND5 levels. Cardiomyocytes derived from a DAND5 full-mutant hiPSC line are more proliferative when compared with gene-corrected hiPSC-CMs. Moreover, parallel cardiac differentiations showed a differential cardiac gene expression profile, with upregulated cardiac progenitor markers in DAND5-KO hiPSC-CMs. Microelectrode array (MEA) measurements demonstrated that DAND5-KO hiPSC-CMs showed prolonged field potential duration and increased spontaneous beating rates. In addition, conduction velocity is reduced in the monolayers of hiPSC-CMs with full-mutant genotype. (4) Conclusions: The absence of DAND5 sustains the proliferation of hiPSC-CMs, which alters their electrophysiological maturation properties. These results using DAND5 hiPSC-CMs consolidate the findings of the in vitro and in vivo mouse models, now in a translational perspective. Altogether, the data will help elucidate the molecular mechanism underlying this human heart disease and potentiates new therapies for treating adult CHD.

Intestinal fibrosis in aganglionic segment of Hirschsprung's disease revealed by single-cell RNA sequencing.

Hirschsprung's disease (HSCR) is a relatively common congenital disability. Accumulating extracellular matrix (ECM) prompts intestinal fibrosis remodelling in the aganglionic segments of HSCR. The contributions of various cellular subsets in the fibrogenesis of HSCR segments are poorly understood. Single-cell transcriptomics from 8 aganglionic segments and 5 normal segments of 7 HSCR subjects and 26 healthy segments of seven healthy donors were analysed. Fibrotic phenotype and alterations were explored using differential expression analysis and single-cell trajectory analysis. Fibrosis-related transcription factors were inferred through single-cell regulatory network inference. Bulk transcriptomic data, proteomic data, immunohistochemistry (IHC) and real-time polymerase chain reaction were used to validate the alterations in the HSCR intestine. Various collagen, fibronectin and laminin protein-coding genes expression were up-regulated in the stromal and glial cells of the HSCR intestine. The number of fibroblasts and myofibroblasts in the aganglionic segments increased, and more myofibroblasts were activated at an earlier stage in HSCR segments, which infers that there is an intestinal fibrosis phenotype in HSCR segments. The fibrotic regulators POSTN, ANXA1 and HSP70 were highly expressed in the ECM-related cellular subsets in the transitional segments and aganglionic segments. The transcription factor regulatory network revealed that fibrosis-related and megacolon-related NR2F1 in the fibroblasts and glial subsets was up-regulated in the aganglionic segment. This work identifies intestinal fibrosis and related regulators in aganglionic segments of HSCR; hence, anti-fibrotic therapy may be considered to prevent HSCR-associated enterocolitis (HAEC), relieve intestinal stricture and improve cell therapy.

Genetic analysis of 55 cases with fetal skeletal dysplasia

BackgroundFetal skeletal dysplasia (SD) is a common congenital disability comprising a complex group of skeletal disorders with substantial clinical and genetic heterogeneity. Many of these defects are detected prenatally using ultrasound (US). However, the diagnostic accuracy of the US is limited.MethodsWe recruited 55 unrelated fetuses with US-detected skeletal anomalies and performed sequential tests using copy number variation sequencing, targeted skeletal gene panel sequencing, or whole exome sequencing. The detected variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification. We conducted breakpoint analysis and structural modeling of variants possibly involved in fetal SD.ResultsA definitive diagnosis was achieved in 81.82% of affected fetuses (45/55). We identified chromosomal abnormalities in seven cases and 36 variants, of which 18 were novel pathogenic or likely pathogenic in 11 genes in 38 cases. De novo variants were identified in 27 cases (71.05%, 27/38), and one gonosomal mosaicism variant was found in the mother of one fetus. Our case examples demonstrated the high heterogeneity of fetal SDs and the rare fetal SD-associated challenges.ConclusionsCareful clinical evaluation of fetuses with SD can guide appropriate molecular testing. Our study extends the SD-associated pathogenic variant spectrum and provides useful genetic counselling guidance and an accurate prenatal diagnosis strategy.

The UA Doppler Index, Plasma HCY, and Cys C in Pregnancies Complicated by Congenital Heart Disease of the Fetus.

Background: Congenital heart disease/defect (CHD) is one of the most common congenital disabilities. Early diagnosis of CHD can improve the prognosis of newborns with CHD. The aim of this study was to evaluate the relationship between the factors and the onset of fetal congenital heart disease by measuring fetal umbilical artery (UA) Doppler index, maternal HCY, and Cys C levels during pregnancy. Methods: This retrospective study analyzed 202 fetuses with CHD, including 77 cases (39.1%) of simple CHD and 120 cases (60.9%) of complex CHD. Singleton pregnant women who were examined at the same time and whose malformation screening did not suggest any structural abnormalities in the fetus were assigned to the control group (n = 400). The UA Doppler index, plasma HCY, and Cys C levels were compared among the pregnant women across the three groups, and logistic regression analysis was performed on statistically significant markers. The ROC of UA S/D, PI, RI, HCY, and Cys C were plotted, and the area under the ROC (AUC) was calculated. Results: The UA S/D, PI, and RI in the complex CHD group were significantly higher than those in the control group (p < 0.05). The levels of HCY and Cys C in the CHD group were significantly higher than those in the control group (p < 0.05). HCY and S/D revealed a positive correlation (r = 0.157), and the difference was statistically significant (p < 0.001). Cys C and S/D were positively correlated (r = 0.131), and the difference was statistically significant (p < 0.05). The levels of UA Doppler indices, maternal plasma HCY, and Cys C were elevated in fetuses with CHD. The AUC of the combined test of the UA index, HCY, and Cys C was higher than that of each individual test. Conclusions: Elevated levels of the UA doppler indices, HCY, and Cys C during pregnancy are positively associated with the development of congenital heart disease in offspring. The combination of HCY and Cys C was the most efficient test for the diagnosis of CHD. We are the first to report that plasma Cys C levels of women pregnant with fetuses with CHD were higher than those of women pregnant with normal fetuses.

Computed Tomography and Other Imaging Modalities in Pediatric Congenital Heart Disease

Congenital heart defects (CHD) are the most common congenital disabilities. Early and accurate diagnosis of coronary heart disease is very important for patients to get timely and effective treatment. In recent years, the accuracy of coronary heart disease diagnosis has been greatly improved with the development of medical imaging equipment and technology. At present, the clinical application of echocardiogram (echo), cardiovascular magnetic resonance (CMR) and computed tomography angiography (CTA) in coronary heart disease anatomy and function has increased significantly, which plays an important role in preoperative diagnosis, intraoperative monitoring, and postoperative recovery evaluation. However, each imaging technique has its indications. Providing the best examination plan for patients requires clinicians and radiologists’ close cooperation. Therefore, this study reviewed the imaging techniques for diagnosing coronary heart disease.

A prospective observational study to evaluate the change in inhibin-B as a marker of sertoli cell function in children subjected to surgical correction for undescended testes

Background and Objectives:Undescended testes (UDT) or cryptorchidism is a common congenital disability characterised by the absence of at least one testicle from the scrotum. The primary aim of surgical correction is to preserve fertility potential and prevent complications including trauma, malignancy, hernia and torsion. Often, children, especially in developing countries, present late with UDT. The effect of surgical correction in the recovery of Sertoli cell function in children aged more than 2 years is not apparent. The present study was conducted to study the change in inhibin-B level as a marker of Sertoli cell function in surgically corrected UDT in a heterogeneous population.Materials and Methods:A prospective observational study conducted over a 3-year period at a tertiary care paediatric surgery centre recruited 76 children with UDT undergoing surgical correction. Inhibin-B as a marker for Sertoli cell function was studied preoperatively and postoperatively. Continuous variables were summarised by calculating mean, standard deviation, median and interquartile range (IQR). Quantile versus quantile plotting was done to assess the distribution of the data. Data were analysed in two groups, with participants aged <2 years (Group A) and more than 2 years (Group B). Wilcoxon signed-rank test was used to compare the pre-operative and post-operative value.Results:In Group A (n =39), the median (IQR) of pre-operative inhibin-B was 181 pg/ml (148–254) and post-operative inhibin-B was 230 pg/ml (176–296). In Group B, the median (IQR) of pre-operative inhibin was 70 pg/ml (44–104) and post-operative inhibin was 102 pg/ml (46–176). There was a significant increase in post-operative inhibin when compared to the pre-operative inhibin (P = 0.015 and 0.012, respectively, in Group A and B). Luteinizing hormone (LH) showed a significant decrease (P = 0.002) in Group A following surgery but bordering on significance in Group B (P = 0.43). On the other hand, follicle-stimulating hormone showed a significant decrease (P < 0.01) in Group B following surgery but not in Group A (P = 0.87).Conclusion:The mean post-operative inhibin-B levels were increased significantly as compared to the pre-operative levels indicating either a successful orchiopexy/adequate germ cell number or both. The benefit of orchiopexy may extend even to children presenting late for evaluation.

Dynamic Changes in Serum Inhibin B Levels in 6- to 24-Month-Old Children Receiving Cryptorchidism Surgery.

ObjectiveCryptorchidism is the most common congenital disability and is defined as the absence of one or both testicles in the scrotum during fetal development. In patients with cryptorchidism, lowered serum inhibin B levels suggest testicular dysfunction. The practical application of serum inhibin B levels in childhood remains controversial. The purpose of this study was to observe the post-operational changes of serum inhibin B levels in patients with cryptorchidism and provide evidence that serum inhibin B is a potential marker for the efficacy of testicular surgery.MethodsA total of 83 male children with cryptorchidism were enrolled in this study. All the children had blood samples taken by venipuncture on the day of surgery. The serum inhibin B levels in the blood samples were measured using an ELISA kit. Paired t-tests were used to assess differences between the groups.ResultsThe results show that, compared with the preoperative values, there was a statistically significant increase in serum inhibin B values one month after the operation in each group (P < 0.05). Compared with the one-month post-operation results, there were no significant changes six months after operation in each group (P>0.05). However, serum inhibin B values decreased significantly in all groups at 12 months post-operation (P < 0.05), suggesting that serum inhibin B values are significantly correlated with age. Correlation analysis showed that serum inhibin B was negatively correlated with age from 6 to 36 months, and the correlation coefficient was −0.488.ConclusionSerum inhibin B can be used as a short-term evaluation index of cryptorchidism surgery rather than as a long-term indicator.

Prevalence and Risk Factors for Hearing Loss in Neonates Admitted to the Neonatal Intensive Care Unit: A Hospital Study.

Introduction: Hearing loss is one of the most common congenital disabilities in neonates. The aims of this study were to investigate the prevalence of hearing loss and identify the most significant risk factor in neonates hospitalized at the Neonatal Intensive Care Unit (NICU).Methods: This cross-sectional study involved 530 neonates admitted to NICU Abuzar Hospital with risk factors for hearing loss based on Joint Committee of Infant Hearing (JCIH). The hearing screening tests include transient evoked otoacoustic emissions (TEOAES) and the automated auditory brain stem response (AABR). For infants with abnormal AABR and TEOAE results, the Auditory Brainstem Response (ABR) and Auditory Steady-State Responses (ASSR) tests were performed.Result: Of 530 infants, 27 (5.09%) were diagnosed with different types of hearing loss. Ototoxic drugs, hyperbilirubinemia requiring exchange transfusion, asphyxia, low weight birth, Apgar score < 5, and a kinship marriage of parents were significant risk factors for hearing loss in our study population.Conclusion: Due to the high prevalence of hearing loss in the NICU, it is recommended that a hearing screening program be performed for all infants admitted to the NICU. Implement a comprehensive plan for neonatal hearing screening for early detection and intervention of hearing loss is essential.

Hemifacial Microsomia Review: Recent Advancements in Understanding the Disease.

Hemifacial microsomia (HFM) is the second most common congenital disability of the face, with a prevalence of 1 in 3000 to 5600 live births. Although etiology is still not fully understood, including both genetics and environmental factors, the latest reports indicate the prominence of premature loss of the neural crest cells. What is more, a deficit of muscles of mastication, except the masseter, correlates in the pathomechanism of mandibular underdevelopment. Due to the significant phenotypic diversification, the typical picture of HFM cannot be determined. It may present as an esthetic concern-minor asymmetry with deformed auricle, and on the contrary, as microtia/anotia with conductive type hearing loss, hypoplastic mandible, and microphthalmia, impairing patient's daily activities. Referring to psychosocial problems, it has been proved that in population with HFM, there is a modestly elevated risk for behavior problems, social competence, and less acceptance. Over the years, more comprehensive methods of assessing the extent and severity of the HFM as the OMENS (+) classification have emerged. The authors like to summarize and present for plastic surgery resident and plastic surgeons the critical features of HFM, including the epidemiology, clinical presentation, pathogenesis, and innovative management reported in the current literature.

The Effect of Moringa oleifera (Lam) Leaf Extracts on Growth of Chicken Embryo Induced by Alkohol

Fetal Alcohol Syndrome (FAS) is a condition associated with drinking alcohol during pregnancy and affect embryo development. FAS is the most common congenital disabilities in the world. The effects of FAS are mental retardation, cranial abnormalities, and heart defects. Moringa oleifera is a highly valued plant. It has an impressive range of biological activities, including antioxidant, antiproliferation, and anti-inflammatory. This study aims to assess the effect of Moringa oleifera leaf extracts in inhibiting growth retardation of chicken embryo growth induced by alcohol. The study was a true experimental design with posttest controlled group design. There were five groups with 5 of chicken embryo each group. The treatments contained 15% alcohol and aquadest as positive control (P+), without alcohol as negative control (P-), P0.5 (0,5g/dl), P5 (5g/dl), P50 (50g/dl) by adding Moringa oleifera leaf extracts, respectively. Moringa oleifera leaf extracts showed the improvement of length and head diameter as a benchmark for chicken embryo development with P5 concentration showed the best results to overcome growth retardation in alcohol-induced chicken embryos. This finding implies against possibility Moringa oleifera leaf extracts can be alternative medicine to prevent growth retardation.

Role of Indian Hedgehog Signaling in Palatal Osteogenesis

Cleft lip-cleft palate is a common congenital disability and represents a large biomedical burden. Through the use of animal models, the molecular underpinnings of cleft palate are becoming increasingly clear. Indian hedgehog (Ihh) has been shown to be associated with craniofacial development and to be active in the palatine bone. The authors hypothesize that Indian hedgehog activity plays a role in osteogenesis within the secondary palate and that defects in this pathway may inhibit osteogenesis of the secondary palate. Palates were isolated from wild-type mice during the period of palate development (embryonic days 9.5 to 17.5). Quantitative real-time polymerase chain reaction was used for detecting gene expression during osteogenic differentiation and cellular differentiation (Shh, Ihh, Ptc1, Gli1, Gli2, Gli3, Runx2, Alp, and Col1a1). Next, palates were analyzed by hematoxylin and eosin, aniline blue, pentachrome, and in situ hybridization to assess osteogenesis of the palatal shelf and expression of hedgehog pathway genes. Finally, the palates of Indian hedgehog-null mice were analyzed to determine the effect of genetic deficiency on palatal development osteogenesis. Increased Indian hedgehog and osteogenic signaling coincided with ossification and fusion of the palate in wild-type mice. This included a fivefold to 150-fold peak in expression of hedgehog elements, including Ihh, at embryonic day 15.5 as compared with embryonic day 9.5. Contrarily, loss of Indian hedgehog by genetic knockout (Ihh-/-) resulted in decreased secondary palate ossification. The authors' results suggest a role for hedgehog signaling during palatal ossification. The hedgehog pathway is activated during palatal fusion, and deletion of Indian hedgehog leads to diminished ossification of the secondary hard palate.

Contractile Properties of Single Permeabilized Muscle Fibers from Congenital Cleft Palates and Normal Palates of Spanish Goats

Analysis of the composition of muscle fibers constituent to a cleft palate could provide significant insight into the cause of velopharyngeal inadequacy. The authors hypothesized that levator veli palatini muscle dysfunction inherent to cleft palates could affect the timing and outcome of cleft palate repair. Single, permeabilized muscle fibers from levator veli palatini muscles of three normal (n = 19 fibers) and three chemically induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were isolated, and contractile properties were evaluated. The maximum isometric force and rate constants of tension redevelopment (ktr) were measured, and the specific force and normalized power were calculated for each fiber. The ktr measures indicate that cleft fibers are predominantly fast-fatigable; normal fibers are slow fatigue-resistant: after a 10-minute isometric contraction, fibers from cleft palates had a loss of force 16 percent greater than that from normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal palates (2226 +/- 143 microm2). Specific forces did not differ between the two groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82 W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12 W/l). There are clear physiologic differences in single muscle fibers from cleft palates and normal palates: cleft palate fibers are physiologically fast, have greater fatigability, and have greater power production. Detection of functional and/or fiber type differences in muscles of cleft palates may provide preoperative identification of a patient's susceptibility to velopharyngeal inadequacy and permit early surgical intervention to correct this clinical condition.

The Young Child with Cleft Lip and Palate: Intervention Needs in the First Three Years

Cleft lip and cleft palate (CL/P) comprise the fourth most common congenital disability and affect approximately 1 out of every 700 children born in the United States. The treatment needs of children with CL/P are numerous and complex, requiring the specialized, coordinated care of an interdisciplinary team. Young children and their families must adapt to the impact of a congenital disability and the subsequent onslaught of emotions, questions, physician appointments, surgeries, and hospitalizations that accompany cleft lip and palate. This article discusses the multiple medical, dental, therapeutic, psychosocial, and early intervention needs faced during the first 3 years of life.