Common Defects Research Articles

Research on wheel–rail impact dynamics due to combined rail weld irregularities and polygonal wheel effects considering 3D contact geometry

The geometric irregularities of rail welds and polygonal wheels are common defects observed in high-speed railways, leading to the generation of high-frequency impact forces and vibrations in the wheel–rail contact system. This research establishes a novel vehicle-track coupled dynamic model that incorporates a 3D wheel–rail contact model using meshing grid and conjugate gradient methods to study the high-magnitude wheel–rail impact forces caused by rail weld irregularities and polygonal wheel combinations. The primary objective of this study is to develop a precise 3D contact model that incorporates the actual geometry of wheel and rail surface irregularities into the calculation of vehicle-track dynamic interactions. The study evaluates the effects of 3D rail weld irregularities and polygonal wheels on wheel–rail dynamic interaction by comparing results with those obtained from a conventional vehicle-track coupled model that considers a 2D contact model. The results show that the lengths and depths of polygonal wheels and rail weld irregularities, as well as vehicle speeds, significantly increase the wheel/rail dynamic impact forces. The results also indicate that the widening of irregularities not only significantly affects the wheel–rail contact force but also has an important influence on the contact stiffness.

Remodeling of adult rat heart subjected to pressure overload from the neonatal period is dependent on the sex

Abstract Background Congenital heart diseases (CHD) represents the most common birth defect. Despite progress in their treatment improving acute survival, there is a paucity of data concerning the long-term consequences of CHD in adults. Purpose Here, we investigate the remodeling in adult rat hearts subjected to pressure overload from the early postnatal period. Methods We used the neonatal abdominal aortic constriction (AAC) model to analyze morphological, functional (by echocardiography), and electrophysiological long-term outcomes. Given the known differences in cardiac pathologies between males (M) and females (F), we focused on the role of sex in cardiac remodeling. Results Our data showed that both sexes exhibited a similar left ventricular weight/body weight ratio at the age of 12 weeks, indicating comparable left ventricle (LV) enlargement as a response to AAC (increase by 103 ± 9 % in M AAC and 99 ± 10 % in F AAC vs. sham-operated animals). However, the right ventricular weight/body weight and lung/ body weight ratios, indicative of LV failing, differed significantly between sexes with better values in F AAC. The favorable cardiac remodeling in F AAC was corroborated by significantly smaller LV systolic and diastolic diameters, along with a lower amount of myocardial fibrosis. Using optical mapping, we revealed preserved longitudinal and transversal conduction velocities (CVL; CVT) in females (CVL 104 ± 8 vs. 109 ± 8 cm/s and CVT 66 ± 7 vs. 59 ± 6 cm/s in F AAC and F Sham, respectively). However, compared to M Sham, the conduction velocities in M AAC showed a significant decrease (CVL 80 ± 3 vs. 92 ± 3 cm/s and CVT 35 ± 2 vs. 54 ± 3 cm/s). Similarly, the amount of connexion 43 (Cx43) and its phosphorylated state (Cx43Ser368) was preserved in F AAC while exhibiting a decrease in M AAC compared to the sham-operated controls. Thus, electrophysiological findings implicate that while the adult M AAC underwent pro-arrhythmogenic remodeling due to the elevated workload, the adult F AAC preserved physiological conduction properties. Conclusion Our data showed different consequences of the increased pressure load exposed from early after birth to the adult M and F heart. These findings highlighted the involvement of both sexes in cardiac studies.

Rare Combination of Congenital Microtia and Limb Malformations: Analysis of Etiology and Treatment.

Congenital microtia is the second most common congenital craniofacial deformity, and limb malformation is the most common birth defect. The combination of the 2 deformities is rare. In this study, the authors present 3 cases with a rare combination of congenital microtia and limb malformations and analyze the etiology and treatment of the malformations. There may be genetic homology between these two malformations, and they can be associated with abnormal ectodermal migration. Level IV-case study.

Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.

Bicuspid Aortic Valve (BAV) is the most common congenital heart defect, affecting at least 2% of the population. The embryonic origins of BAV remain poorly understood, with few assays for validating patient variants, limiting the identification of causative genes for BAV. In both human and mouse, the left and right leaflets of the arterial valves arise from the outflow tract cushions, with interstitial cells originating from neural crest cells and the overlying endocardium through endothelial-to-mesenchymal transition (EndoMT). In contrast, an EndoMT-independent mechanism of direct differentiation of cardiac progenitors from the second heart field (SHF) is responsible for the formation of the anterior and posterior leaflets. Defects in either of these developmental mechanisms can result in BAV. Although zebrafish have been suggested as a model for human variant testing, their naturally bicuspid arterial valve has not been considered suitable for understanding human arterial valve development. Here, we have set out to investigate to what extent the processes involved in arterial valve development are conserved in zebrafish and ultimately, whether functional testing of BAV variants could be carried out. Using a combination of live imaging, immunohistochemistry and Cre-mediated lineage tracing, we show that the zebrafish arterial valve primordia develop directly from SHF progenitors with no contribution from EndoMT or neural crest, in keeping with the human and mouse anterior and posterior leaflets. Moreover, once formed, these primordia share common subsequent developmental events with all three aortic valve leaflets. Our work highlights a conserved ancestral mechanism of arterial valve leaflet formation from the SHF and identifies that development of the arterial valve is distinct from that of the atrioventricular valve in zebrafish. Crucially, this confirms the utility of zebrafish for understanding the development of specific BAV subtypes and arterial valve dysplasia, offering potential for high-throughput variant testing.

The Analysis of the Fetal Abdominal Wall and Gastrointestinal Tract Abnormalities in a Single Tertiary Center

OBJECTIVE: We aimed to evaluate the fetuses with gastrointestinal anomalies and anterior abdominal wall defects detected in the prenatal period in our clinic and to analyze their perinatal outcomes. STUDY DESIGN: This retrospective study analyzed the data of 67 cases evaluated by the perinatology department of the Basaksehir Cam and Sakura City Hospital between January 2021 and May 2023 with a diagnosis of fetal anterior abdominal wall and gastrointestinal tract abnormalities. RESULTS: A total of 67 cases were included in our study with a mean maternal age of 26.4 ± 3.1 years and a median gestational week of first assessment at our center of 22 weeks (12-39 weeks). The most common anterior abdominal wall malformations were omphalocele (n=29, 43.3%) and gastroschisis (6 cases, 9.0%), and the most common fetal gastrointestinal tract anomalies were duodenal atresia (n=10, 14.9%), dilated bowel (n=5, 7.4%), and intestinal atresia (n=4, 5.9%). While genetic testing was carried out in 18 cases (27%), chromosomal abnormality was found in 6 (9.0%) cases. Termination of pregnancy was performed in 6 cases (9.0%). Postnatally, surgery was performed in 49 cases (73.1%) with a diagnosis of postpartum omphalocele, duodenal atresia, gastroschisis, intestinal and anal atresia. An uneventful surgical course was recorded for 47 cases that underwent surgery. CONCLUSION: The most common abdominal wall defects are omphalocele and gastroschisis, and the most frequent gastrointestinal anomalies are small bowel abnormalities (duodenal atresia, dilated bowel, intestinal atresia) in our study cohort. These abnormalities might be an isolated anomaly or part of a syndrome or associated with chromosomal abnormalities. The prognosis for infants with gastrointestinal malformation depends on the presence of associated anomalies or karyotype anomalies.

Advances in myocardial energy metabolism: metabolic remodeling in heart failure and beyond.

The very high energy demand of the heart is primarily met by ATP production from mitochondrial oxidative phosphorylation, with glycolysis providing a smaller amount of ATP production. This ATP production is markedly altered in heart failure, primarily due to a decrease in mitochondrial oxidative metabolism. Although an increase in glycolytic ATP production partly compensates for the decrease in mitochondrial ATP production, the failing heart faces an energy deficit, that contributes to the severity of contractile dysfunction. The relative contribution of the different fuels for mitochondrial ATP production dramatically changes in the failing heart, which depends to a large extent on the type of heart failure. A common metabolic defect in all forms of heart failure (including HFrEF, HFpEF, and diabetic cardiomyopathies) is a decrease in mitochondrial oxidation of pyruvate originating from glucose (i.e. glucose oxidation). This decrease in glucose oxidation occurs regardless of whether glycolysis is increased, resulting in an uncoupling of glycolysis from glucose oxidation that can decrease cardiac efficiency. The mitochondrial oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in HFpEF and diabetic cardiomyopathies myocardial fatty acid oxidation increases, while in HFrEF myocardial fatty acid oxidation either decreases or remains unchanged. The oxidation of ketones (which provides the failing heart with an important energy source) also differs depending on the type of heart failure, being increased in HFrEF, and decreased in HFpEF and diabetic cardiomyopathies. The alterations in mitochondrial oxidative metabolism and glycolysis in the failing heart are due to transcriptional changes in key enzymes involved in the metabolic pathways, as well as alterations in redox state, metabolic signaling, and posttranslational epigenetic changes in energy metabolic enzymes. Of importance, targeting the mitochondrial energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac function and cardiac efficiency in the failing heart.

Suppressing Se Vacancies in Sb2Se3 Photocathode by In Situ Annealing with Moderate Se Vapor Pressure for Efficient Photoelectrochemical Water Splitting.

Sb2Se3 emerges as a promising material for solar energy conversion devices. Unfortunately, the common deep-level defect VSe (selenium vacancy) in Sb2Se3 results in a low solar conversion efficiency. The post selenization process has been widely adopted for suppressing VSe. However, the effect of selenization on suppressing VSe is often compromised and even more VSe are induced due to defect-correlation. Herein, high-quality Sb2Se3 films are prepared using an unconventional selenization process, with precisely regulating in situ annealing Se vapor pressure. It is found that moderate Se vapor pressure annealing can efficiently suppress VSe by overcoming defect-correlation, as well as promotes grain growth and forms a better heterojunction band alignment. Consequently, the Sb2Se3 photocathode shows a high-level photocurrent of 19.5 mA cm-2 at 0 VRHE, an onset potential of 0.40 VRHE and a half-cell solar-to-hydrogen conversion efficiency of 1.9%, owing to the inhibited charge recombination, excellent charge transport and interface charge extraction. This work provides a significant insight to suppress deep-level defect VSe by adjusting Se vapor pressure for efficient Sb2Se3 photocathode.

Anesthetic management of laparoscopically assisted fetoscopic surgery to correct spina bifida

Introduction. The growing incidence of intrauterine pathology in the fetus at the present stage dictates the need to develop and improve intrauterine surgical correction of defects in the fetus. Myelomeningocele (SPINA BIFIDA) is the most common and severe neural tube defect in the fetus, the severity of the neurological deficit is determined by the level of location and extent of the anomaly. By uniting doctors of various specialties (obstetricians-gynecologists, neonatologists, surgeons, anesthesiologists-resuscitators), the Clinic of the St. Petersburg State Pediatric Medical University effectively introduces methods of prenatal surgery.The objective was to demonstrate by clinical example the experience of successful fetoscopic correction of myeloneningocele to reduce maternal risks and injuries, to reduce risks aimed at protecting the tissues of the spinal cord of the fetus, as well as to reduce the need for postpartum correction of the defect in the fetus, to improve prognosis and risks of subsequent disability.Materials and methods. The article presents the first successful experience of minimally invasive laparoscopic correction of myelomeningocele in the fetus with the participation of the multidisciplinary team and the features of anesthesiological support of the method.Conclusion. Laparoscopic access, together with the optimal choice of anesthetic management in fetal surgery, allows not only to successfully correct the defect in myelomeningocele in the fetus, but also to significantly minimize and reduce the risks of injury to the mother, and also reduces the need for postpartum surgical treatment and reduce disability. Accumulation and improvement of experience, a multidisciplinary approach is the key to successful correction of intrauterine fetal pathology.

Bridges and viaducts in Brazil: an analysis of the predominant defects

Bridges and viaducts are essential structures for mobility and transportation but are susceptible to defects that can impact safety and durability. Defect studies are crucial for identifying issues and solutions, assessing the condition of the structures, and determining the need for intervention. Visual inspections were conducted on five structures in the state of Rio de Janeiro, and the defects found were either identical or similar to those reported in the literature review referenced in this study. Based on this information, it is possible to identify the most common defects and focus preventive and corrective maintenance efforts to prevent the progression of these issues and minimize the financial costs associated with structural repairs. The methodology used in this work involved the analysis of bibliographic sources, scientific articles and visual inspections.

PREVALENCE AND QUALITY OF RESTORATIVE STRUCTURES OF PERMANENT TEETH IN CHILDREN FROM LOWLAND AND MOUNTAINOUS AREAS OF THE TRANSCARPATHIAN REGION OVER THE COURSE OF OBSERVATION

Introduction: Treatment of invasive forms of caries involves the removal of demineralized hard tooth tissues and the restoration of anatomical integrity using various types of restorative materials. The choice and conditions of use of these materials have clear indications. However, the durability of restorative structures, even with strict adherence to the algorithm, is not always sufficient, especially among children living in areas with biogeochemical deficiencies. Objectives: The aim of this study was to analyze the prevalence of fillings made from different restorative materials in the permanent teeth of children living in lowland and mountainous geographical areas of the Transcarpathian region and to determine the percentage of defects in restorative structures over time. Methods: For the analysis, 525 medical records of dental patients (form 043) from two geographical areas of the Transcarpathian region were selected, specifically from Uzhhorod, University Dental Clinic LLC, and Rakhiv, the dental office of the Rakhiv District Hospital. The period of dental treatment covered was from 2018 to 2022. Paraclinical content analysis was performed to determine the number of direct and indirect restorative structures and to assess the occurrence of defects and their loss at 6 and 12 months post-treatment. Statistical probabilities and errors were determined using the computer program STATISTICA 6.1. Results. The rates of patient visits for the restoration of indirect restorations of permanent teeth in children living in the mountainous zone differ from those in children from the lowland zone of residence significantly after 6 months (4.0%; 2.1%; p<0.05), and not significantly after 12 months (10.0%; 10.5%; p>0.05). Comparing the incidence of defects, impaired fixation, or loss of various types of restorative structures in permanent teeth in children living in lowland and mountainous areas of the Transcarpathian region, it was found that the most common defects or loss of fillings made of glass ionomer cements occurred both after 6 and 12 months. The percentage distribution of the appearance of defects or loss of restorative structures made in the permanent teeth of children living in the mountainous zone from glass ionomer cements, light-curing composites on indirect restorations is 6 months (7.2%, 6.0%, 4.0%, p>0.05) and 12 months (16.3%, 11.1%, 10.0%, p>0.05). The differences are not significant. In the permanent teeth of children living in the low-lying area, the percentage of defects or loss of restorative structures made of glass ionomer cements, light-curing composites on indirect restorations is 6 months (6.7%, 4.4%, 2.1%, p<0.05) and 12 months (20.0%, 9.6%, 10.5%, p<0.05). The differences are significant. Conclusions: Thus, when comparing the percentage of defects in various restorative structures and their loss in the permanent teeth of children living in the lowland and mountainous areas of the Transcarpathian region, no significant differences were found. Specifically, for glass ionomer cements, the defect percentages were 6.7% and 7.2% after 6 months (p > 0.05) and 20.0% and 16.3% after 12 months (p > 0.05). For direct composite restorations, the defect percentages were 4.4% and 6.0% after 6 months (p > 0.05) and 9.6% and 11.1% after 12 months (p > 0.05). For indirect composite restorations, the defect percentages were 2.1% and 4.0% after 6 months (p > 0.05) and 10.5% and 10.0% after 12 months (p > 0.05). This indicates that the differences in the percentage of defects between the lowland and mountain zones are not statistically significant for any of the types of restorative structures during the specified periods.

Scanning Electron Microscopic Evaluation of Surface Defects of Remover Retreatment File After Single and Multiple Uses.

This study aimed to evaluate surface defects of Remover rotary Nickel-Titanium (NiTi) files after single and multiple uses in conventional endodontic retreatment procedures using scanning electron microscopy (SEM). Eighty acrylic blocks, simulating root canals with a 1.5 mm internal diameter, a 5 mm radius of curvature, and a 55° curvature, were utilized. After chemomechanical preparation and obturation, 24 new Remover files (N30, 7%, L23) were randomly assigned to three groups: single use, triple use, and six uses. The files were operated at 600 rpm with a torque of 2.5 Ncm, cleaned, and sterilized after each use. SEM analysis at magnifications of 100x, 250x, and 500x revealed surface defects, including tip deformation, microcracks, fracture, unwinding, surface pitting, and blade disruption. Deformation was observed in 75% of the files after a single use and in 100% of the files after three and six uses. Microcracks were absent after single use but appeared in 25% and 87.5% of files after three and six uses, respectively, showing a statistically significant increase (p < 0.001). Surface pitting also significantly increased among groups (p = 0.004). No fractures were observed in any group. The most common defects were tip deformation (91.7%) and surface pitting (70.8%). The findings suggest that repeated use of NiTi files significantly increases surface defects, elevating the risk of fatigue fractures. Thus, the results recommend limiting the reuse of Remover files to a maximum of 3x. Further research is needed to correlate defect types with anatomical factors and to assess file effectiveness in retreatment scenarios.

Strong Dependence of Point Defect Properties in Metal Halide Perovskites on Description of van der Waals Interaction.

Weaker than ionic and covalent bonding, van der Waals (vdW) interactions can have a significant impact on structure and function of molecules and materials, including stabilities of conformers and phases, chemical reaction pathways, electro-optical response, electron-vibrational dynamics, etc. Metal halide perovskites (MHPs) are widely investigated for their excellent optoelectronic properties, stemming largely from high defect tolerance. Although MHPs are primarily ionic compounds, we demonstrate that vdW interactions contribute ∼5% to the total energy, and that static, dynamics, electronic and optical properties of point defects in MHPs depend significantly on the vdW interaction model used. Focusing on widely studied CsPbBr3 with the common Br vacancy and interstitial defects, we compare the PBE, PBE+D3, PBE+TS, PBE+TS/HI and PBE+MBD-NL models and show that vdW interactions strongly alter the global and local geometric structure, and change the fundamental bandgap, midgap state energies and electron-vibrational coupling. The vdW interaction sensitivity stems from involvement of heavy and highly polarizable chemical elements and the soft MHP structure.

Polysaccharide-based hydrogels for cartilage regeneration.

Cartilage defect is one of the common tissue defect clinical diseases and may finally lead to osteoarthritis (OA) which threat patients' physical and psychological health. Polysaccharide is the main component of extracellular matrix (ECM) in cartilage tissue. In the past decades, polysaccharide-based hydrogels have shown great potential for cartilage regeneration considering unique qualities such as biocompatibility, enhanced cell proliferation, drug delivery, low toxicity, and many others. Structures such as chain length and chain branching make polysaccharides have different physical and chemical properties. In this review, cartilage diseases and current treatment options of polysaccharide-based hydrogels for cartilage defection repair were illustrated. We focus on how components and structures of recently developed materials affect the performance. The challenges and perspectives for polysaccharide-based hydrogels in cartilage repair and regeneration were also discussed in depth.

A Novel Self-Retentive Obturator to Facilitate Feeding in an Infant with Cleft Palate: A Case Report and Literature Review.

Cleft lip and palate are common congenital defects with multifactorial complex etiology characterized by complete or incomplete cleft of lip, alveolus, and hard and soft palate. In infants, the main problem lies in the difficulty of suckling with frequent nasal regurgitation leading to respiratory and middle ear infections. This article presents a case report of an 8-day-old female with complete cleft of hard and soft palate who was given a novel self-retentive type feeding obturator. This obturator eliminated the need for supplementary aids to help in retention and has a simple design, is cost-effective, and easy to use.

Flatness jump phenomenon in cold-rolled steel strip with high temperature: Root cause and solution

The steel strip produced in the 20-high cold rolling mill has the characteristic of high temperature in a certain factory, and a rare strip flatness phenomenon occurs in the fourth pass, different from the common flatness defects, the flatness value of each position in the strip width shows an irregular and drastic fluctuation state along with time, and it is called the flatness jump phenomenon, which seriously affects the stability of the rolling process and the production efficiency. Aiming at this problem, a method combining the rolling experiment with the numerical simulation is used to study its generation mechanism and seek for effective control technique. Through the thermal imaging measurement and the analysis of the production data, the temperature fluctuation in the fourth pass is the main reason for the flatness jump, which is related to the nucleate boiling state when the emulsion impacts on the high-temperature strip surface in the cooling process. Based on the rolling control experiments of different cooling factors, the critical temperature range for the occurrence of flatness jump is determined, which is used for the improvement of cooling technique subsequently, and the range of emulsion exit flow is optimized to 500 L/min ∼ 2050 L/min. The rolling experiment is carried out in the industrial field, it is found that the production process is stable and the flatness jump does not appear, with the small value basically within the range of ± 10 IU, and the scheme is planned for long-term application after a period of optimization, which could ultimately enhance the stability of the rolling process and the performance of finished product. Further, the paradigm and information provided in this work would be beneficial for understanding the formation mechanism of the similar complicated flatness phenomenon in cold rolling and optimizing the industrial applications of cooling technology.

Imaging and reconstruction of asymmetric wrinkles in carbon fibre composites using high-frequency eddy current and full matrix capture-based ultrasound

Ply wrinkles are a common defect found in Carbon Fiber Reinforced Polymer (CFRP) laminates that can lead to failure in composite structures if not correctly evaluated during manufacture stages. The mechanical performance of a structure depends on multiple parameters of a wrinkle, such as amplitude, wavelength, and asymmetry, which ideally need to all be measured to characterise the wrinkle properly. To address this issue, the authors designed and manufactured a set of complex wrinkles with various asymmetry offsets and amplitude and obtained raw data by testing them with a high-frequency eddy-current system. A unique trajectory in the complex Nyquist plot was found on asymmetric wrinkles, demonstrating the dominant influence of wrinkle asymmetry on electrical resistance. The authors also used full matrix capture ultrasound to characterise the wrinkles and measured the profiles by extracting texture phase randomness. The study revealed the superior capability of FMC UT for characterising and retrieving the profile in wrinkle coupons, while HF ECT was more adaptable for identifying the region of interest effectively. This work also implements a state-of-the-art deep fusion strategy to demonstrate a lightweight architecture can be easily used to combine multiple sources of wrinkle profiles and generate a more accurate prediction than traditional methods. Overall, the demonstrated work can be further applied to CFRPs with increasing geometric complexity and defects to facilitate the design efficiency and testing of CFRP components.

8610 The Role of Adenylyl Cyclase 2 Gene-Dosage Changes in Congenital Male Genitourinary Anomalies

Abstract Disclosure: D.J. Lamb: Advisory Board Member; Self; Ro Health, Inc. Stock Owner; Self; Fellow Health, Inc. M.A. O'Neill: None. Collectively, congenital genitourinary (GU) birth defects are the most common birth defects in males, yet relatively little is known about their cause. In part, this reflects the current clinical perspective that, because most of these birth defects can be surgically repaired, there is nothing to be gained by understanding the cause. Yet our studies show that seemingly simple birth defects like hypospadias or cryptorchidism, may be associated with other more significant underappreciated defects, such as those affecting the kidney, heart, eyes or behavior. We tested the hypothesis that chromosome microdeletions and microduplications (called copy number variations, CNVs) result in gene-dosage changes that are important regulators of GU development and when haploinsufficient or duplicated normal genitourinary development is impacted causing birth defects of the upper and/or lower genitourinary tract. We successfully used this strategy to identify 15 different previously unrecognized genes that when microduplicated or microdeleted result in conditions such as cryptorchidism, hypospadias, disorders of sexual differentiation (DSD) and other anomalies. Remarkably, gene-dosage changes affected major signaling pathways and post-translational modifications in novel, previously unrecognized ways. Herein, we focused on defining the role of a candidate gene commonly microdeleted or microduplicated in patients with cryptorchidism, hypospadias and/or micropenis. Locus mapping allowed identification of adenylate cyclase 2 (ADCY2) as a candidate gene at the 5p15.31 Cri-du-Chat region in patients with male genital tract anomalies. ADCY2 CNVs were more common in non-syndromic patients with micropenis, cryptorchidism, and/or hypospadias (1.6%) than the general population (0.07%; p&amp;lt; 0.001). Whole exome sequence studies revealed a range of phenotypic anomalies in patients with damaging and potentially damaging ADCY2 variants in addition to the male GU anomalies, including congenital anomalies of the kidney and urinary tract. It is our hypothesis that ADCY2 duplications result in a de-sensitization of the LH receptor diminishing testosterone biosynthesis in the testis, whereas deletions diminish LH receptor signaling. ADCY2 CNVs were assessed in 100 men with spermatogenic failure who were born with cryptorchidism. The ADCY2 CNV frequency was the same as in our cohort of boys with GU anomalies, but as adults they also have hypergonadotropic hypogonadism, which we predicted if ADCY2 over-expression was impacting adult Leydig cell steroidogenesis through partial desensitization of the LH receptor. These studies identified an unrecognized cause of GU anomalies. In the future, such knowledge may lead to improved diagnosis and therapeutic approaches to ameliorate these common birth defects. Presentation: 6/2/2024

Visual Field Patterns in Optic Neuropathy

The optic nerve is susceptible to a wide variety of pathological processes. In optic neuropathy, quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guiding treatment plans. While acquired visual field defects may progress rapidly, congenital visual field defects may not progress or may progress slowly. Although the most common defect in congenital or acquired optic neuropathy is the central defect, many defect types that are not pathognomonic to the disease can be seen. In ischemic optic neuropathy, which is common among optic neuropathies, arcuate defect and central defect are usually seen. In disc disorders with localized nerve damage, such as optic disc coloboma or optic pit, localized defects such as arcuate scotoma or cecocentral scotoma in which the fixation point is preserved may be observed. Papilledema causes peripapillary fluid accumulation and an enlarged blind spot in the perimetry. In compressive optic neuropathies, non-specific defects such as central and subtudinal defects may be observed, as well as quadrant defects such as hemianopsia and quadrionopsia. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine structure-function relationships improves clinical care in neuro-ophthalmic disorders.

First diagnosis of severe coarctation of the aorta necessitation percutaneous intervention during pregnancy, a case report

Abstract Background Coarctation of the aorta (CoA) is a common congenital heart defect that affects about 3-4 in every 10,000 live births. Despite clear signs on clinical examination, the diagnosis is sometimes not made until adulthood. An increasing number of patients with CoA are reaching child-bearing age. Unrepaired CoA or severe recurrent stenosis during pregnancy is a significant concern, as it poses a high risk of maternal and foetal complications and even death. Case summary A 21-year-old women was referred to the cardiology department at 17 weeks’ gestation for management of arterial hypertension and unexplained systolic murmur. She had been diagnosed with hypertension elsewhere the year before presentation, but unfortunately this remained unexplored. She had been started on labetalol early in the pregnancy. Clinical examination showed a loud systolic heart murmur extending from parasternal to subclavicular and scapular areas. Pulses in the lower extremities were very weak and blood pressure was slightly elevated with a significant gradient between the upper and lower extremities. Echocardiography showed remarkable absence of pulsatile flow in the abdominal aorta and narrowing just distal to the subclavian artery with typical diastolic tail pattern on suprasternal imaging. Cardiac magnetic resonance confirmed the presence of a severe coarctation distal to the subclavian artery and presence of multiple collaterals allocating this patient in the extremely high-risk category with a risk of up to up 40-100% of maternal cardiac event during pregnancy. An extensive multidisciplinary team meeting was convened. After initial medical optimisation, increased claudication and signs of placental hypoperfusion necessitated an endovascular procedure under general anaesthesia at 23 weeks’ gestation. A Bentley BeGraft Plus stent (16x38 mm) was successfully placed. Postoperative ultrasound showed biphasic placental perfusion and normalisation of blood pressure and ankle-brachial indices. At 36 weeks’ gestation, the patient gave birth to a healthy child. Conclusion CoA should be considered in any young patient with arterial hypertension. Altered maternal haemodynamics during pregnancy resulted in severe symptomatic CoA and reduced placental flow necessitating percutaneous intervention during pregnancy. A multidisciplinary pregnancy heart team is essential for optimal treatment management in these high-risk patients.

7534 Characterizing The Presentation Of Non-Classical Congenital Adrenal Hyperplasia

Abstract Disclosure: S. Patel: None. M. Skamagas: None. A.C. Levine: None. M. Yau: None. Introduction: 21-hydroxylase deficiency, due to CYP21A2 gene mutations, is the most common steroidogenic enzymatic defect causing congenital adrenal hyperplasia (CAH). Disease severity is categorized into the classical and milder, non-classical (NCAH) form. Many patients go undiagnosed due to variable presentation and delayed onset. We aim to investigate the specific presenting concerns, age of onset, and genotypes associated with NCAH. Methods: A retrospective chart review of 285 patients with CAH seen over the past 2 years at our academic pediatric and adult endocrine clinics was performed. Records were reviewed for presenting concerns and age of symptom onset. CYP21A2 gene analysis was performed commercially via multiplex ligation-dependent probe amplification or next generation sequencing. Results: Of the 165 patients classified with NCAH, genotypes were available for 124 patients. Of the patients with a V281L allele, 43 were homozygous and 49 were heterozygous. 7 patients had the P30L allele and 7 had other allele combinations. The overall most common presenting concerns were early pubarche (29%), hirsutism (28%), and irregular menses (26%). In V281L homozygotes, family history most commonly led to diagnosis (30%). In patients with V281L heterozygosity or the P30L allele, the predominant concern was early pubarche (37% and 43% respectively). 15% of patients were screened prenatally or only due to family history and were asymptomatic at diagnosis. Patients’ age at diagnosis ranged from 0-40 years, with the mean age at diagnosis for the total group being 13.3 ± 8.9 years. Mean age of onset in symptomatic V281L homozygotes (15.4 ± 7.9 years) trended toward an older age compared to symptomatic V281L heterozygotes (15.1 ± 10.5 years) (P value = 0.90). Those who were heterozygous for V281L/P30L or undetermined whether homozygous for V281L or heterozygous with a deletion were excluded from age of onset comparisons. Discussion: The mean age of symptom onset was in adolescence and did not differ significantly between V281L homozygotes and heterozygotes. Early pubarche is a frequent presenting symptom in children with NCAH, and our data support this finding. P30L has been associated with a more severe phenotype than V281L, and in our cohort, the only patient presenting in adrenal crisis had a genotype with a P30L mutation. As NCAH is one of the most common autosomal recessive disorders in humans and there is an allelic predominance of V281L in NCAH patients, it is not surprising that a large percentage of V281L homozygotes were diagnosed due to family history prior to developing symptoms. Such patients need to be followed clinically and our data describing symptom onset could be useful in counseling these families and those with prenatal diagnoses. Presentation: 6/1/2024