Normal Development Research Articles

Deep Spectral Library of Mice Retina for Myopia Research: Proteomics Dataset generated by SWATH and DIA-NN

The retina plays a crucial role in processing and decoding visual information, both in normal development and during myopia progression. Recent advancements have introduced a library-independent approach for data-independent acquisition (DIA) analyses. This study demonstrates deep proteome identification and quantification in individual mice retinas during myopia development, with an average of 6,263 ± 86 unique protein groups. We anticipate that the use of a predicted retinal-specific spectral library combined with the robust quantification achieved within this dataset will contribute to a better understanding of the proteome complexity. Furthermore, a comprehensive mice retinal-specific spectral library was generated, encompassing a total identification of 9,401 protein groups, 70,041 peptides, 95,339 precursors, and 761,868 transitions acquired using SWATH-MS acquisition on a ZenoTOF 7600 mass spectrometer. This dataset surpasses the spectral library generated through high-pH reversed-phase fractionation by data-dependent acquisition (DDA). The data is available via ProteomeXchange with the identifier PXD046983. It will also serve as an indispensable reference for investigations in myopia research and other retinal or neurological diseases.

Shared Accountability Shaping the Destinies of Individual and Groups of Nonhuman Primates

At the California National Primate Research Center (CNPRC), the preferred housing for rhesus macaques involves maintaining them in complex social groups outdoors, primarily for breeding purposes. This functionally appropriate environment promotes effective coping through the expression of species-typical behaviors and important aspects of species-typical social structure, thus enabling normal animal development, higher reproductive success, and the production of high-quality biological models. Despite the benefits, social housing introduces challenges like trauma from aggressive interactions. These challenges necessitate a delicate balance between tolerating some aggression and preventing repeated targeting of individuals. Therefore, the CNPRC has established a multidisciplinary working group of behavioral management experts, veterinarians, animal care, and researchers that meets regularly to review cases of animals that may need to be removed from their social group. We discuss the criteria and decision-making processes employed to manage and mitigate aggression. We describe the systematic approach to identifying at-risk individuals and the comprehensive evaluation process that guides whether to relocate an animal from their groups or not. Considerations include the welfare of the individual and the group’s social stability. This paper provides case studies demonstrating how the working group applies these criteria and processes in practical scenarios, highlighting the complexities and challenges of such decisions.

Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish.

Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, N-terminal acetylation, is catalyzed by NAA80 in humans. N-terminal acetylation of actin is crucial for maintaining normal cytoskeletal dynamics and cell motility in human cell lines. However, the physiological impact of actin N-terminal acetylation remains to be fully understood. We developed a zebrafish naa80 knockout model and demonstrated that Naa80 acetylates both muscle and non-muscle actins in vivo. Assays with purified Naa80 revealed a preference for acetylating actin N-termini. Zebrafish lacking actin N-terminal acetylation exhibited normal development, morphology, and behavior. In contrast, humans with pathogenic actin variants can present with hypotonia and hearing impairment. Whereas zebrafish lacking naa80 showed no obvious muscle defects or abnormalities, we observed abnormal inner ear development, small otoliths, and impaired response to sound. In conclusion, we have established that zebrafish Naa80 N-terminally acetylates actins in vitro and in vivo, and that actin N-terminal acetylation is essential for normal hearing.

Acalvaria, rare congenital malformation in palestine: case report and literature review

Introduction and Importance: Acalvaria is a rare congenital anomaly characterized by absent cranial vault bones, often misdiagnosed as anencephaly or encephalocele. Case Presentation: We present a case of a 10-day-old male neonate with Acalvaria, delivered normally at 37+5 weeks, with a birth weight of 2.7 kg and dysmorphic features including low-set ears and a sandal gap. Skull X-ray revealed absent parietal, temporal, and frontal bones. Initially admitted for potential sepsis, he has since shown normal development at three months, with ongoing conservative management. Clinical Discussion: Acalvaria is a rare congenital malformation marked by the absence of cranial vault bones, dura mater, and scalp muscles. Our case presents partial calvaria absence with normal skull base, classified as primary acalvaria. Associated anomalies necessitate thorough evaluation for prognosis. Diagnosis can occur as early as 12 weeks gestation via ultrasound, but management remains conservative, focusing on supportive care and monitoring for potential surgical interventions later. Conclusion: Acalvaria is a rare, fatal anomaly requiring conservative management; antenatal care and psychological preparation are essential for affected families.

Delta neutrophil index (DNI) as a potential biomarker for fetal growth restriction: insights from maternal hematological changes and neonatal outcomes

BackgroundThis study investigates the role of Delta Neutrophil Index (DNI), an inflammation marker, in late-onset fetal growth restriction (LO-FGR) and its prediction of composite adverse neonatal outcomes.MethodsA retrospective study was conducted on 684 pregnant women (456 with normal fetal development and 228 with LO-FGR) who delivered at Health Sciences University Etlik Zubeyde Hanim Women’s Health Training and Research Hospital between January 1, 2015, and June 30, 2018. Composite adverse neonatal outcomes were defined as at least one of the following: 5th minute APGAR score < 7, respiratory distress syndrome (RDS), or neonatal intensive care unit (NICU) admission.ResultsThe FGR group had significantly higher levels of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and DNI compared to controls (p < 0.05, for all). For FGR diagnosis, the DNI demonstrated the highest area under the curve (AUC = 0.677, 95% CI: 0.642–0.711) with a cut-off value of > -2.9, yielding a sensitivity of 78.41%, a specificity of 52.97%, a positive likelihood ratio (+ LR) of 1.68, and a negative likelihood ratio (-LR) of 0.37 (p < 0.001). For predicting composite adverse neonatal outcomes in the FGR group, DNI again demonstrated superior performance with an AUC of 0.635 (95% CI: 0.598–0.670), a cut-off value of > -2.2, a sensitivity of 69.90%, a specificity of 55.36%, a + LR of 1.56, and a -LR of 0.51 (p < 0.001). NLR, PLR, and MLR had AUCs below 0.55, indicating poor discriminative ability, with none reaching statistical significance.ConclusionThis study highlights the potential role of DNI as a promising biomarker for detecting inflammatory processes associated with LO-FGR and its complications.

Diagnosis and management of pituitary adenomas in children and adolescents.

Pituitary adenomas (PA) - also now called pituitary neuroendocrine tumours or Pit-NETS - are rare in children and adolescents, and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. We will review recent knowledge on the epidemiology, clinical features, diagnosis and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. Paediatric PA present multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor Interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

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

6367 Growth gone Awry: A Rare Case of Acromegaly in a 16-Year-Old Female with Panhypopituitarism Secondary to Craniopharyngioma on Low Doses of Growth Hormone with Low IGF-1 levels

Abstract Disclosure: L.M. Ayala Castro: None. J. Ye Tay: None. A. Diaz: None. This report highlights a rare case of a 16-year-old female with panhypopituitarism due to craniopharyngioma, where GH replacement therapy triggered acromegaly features despite having low IGF-1 levels. Background: Craniopharyngiomas are the most common tumors causing acquired pituitary deficiencies in children. Various mechanisms contribute to acromegaly, and hypersensitivity to hormonal treatment in this benign tumor emerges as a plausible avenue for investigation. Case Presentation: A 16-year-old female diagnosed with craniopharyngioma at age 5 developed secondary panhypopituitarism. Baseline hormonal profiles indicated markedly reduced levels of IGF-1 and insulin growth factor–binding protein 3 (IGF-BP3). Despite the established condition, GH treatment was initiated at age 8 for potential growth and development benefits. Before commencing GH therapy, a bone age assessment revealed normal skeletal development. However, GH replacement therapy led to an unexpectedly robust response, resulting in physical changes consistent with acromegaly. Paradoxically, laboratory evaluations showed low IGF-1 levels. Imaging studies, including pituitary MRI, ruled out new abnormalities or tumors. As the patient approached peak adult height at 16, having been on adult GH therapy since age 13, a decision was made to discontinue GH replacement therapy and address acromegaly symptoms. Frequent follow-up visits were planned to assess growth velocity, monitor hormonal levels, and evaluate potential adverse effects. Discussion: This case demonstrates an unusual sensitivity to exogenous GH, resulting in an exaggerated response contrary to expected IGF-1 elevation. Atypical IGF-1 levels may suggest alterations in liver physiology, GH receptor signaling pathways (e.g., Laron Syndrome), or downstream defects in IGF-1 synthesis. Further research is crucial to elucidate the underlying mechanisms. Conclusion: Only 3 cases of acromegaly as a side effect of GH replacement therapy have been reported in the literature. We report a further case that underscores the complexity of managing hormonal imbalances, especially in unique patient populations with panhypopituitarism secondary to craniopharyngioma. The unexpected response to GH treatment emphasizes the need for individualized approaches and vigilant monitoring.

Vertebral deformities in cultured big size Rainbow Trout: Radiological analysis from juvenile to harvest size

Vertebral deformities are a big challenge in Rainbow Trout seawater aquaculture. However, supportive scientific literature is missing. The present study used radiology to follow the development of vertebral deformities in a population of farmed Rainbow Trout as they grew from 36 g to 5.5 kg. In addition, separately collected deformity screening data from three other farmed populations were included for comparison.The fish developed deformities in different vertebral regions over time, eventuating to affect almost the entire vertebral column. At this point, the fish were ∼ 5.5 kg and 93 % of the fish had one or more deformed vertebrae. A negative relationship between severity of deformity (number of deformed vertebrae per individual), and fish length and weight strongly suggest a negative impact on fish welfare. The most frequently affected area was the ural region of the vertebral column. This region is a part of the caudal fin complex which also suffered from degradation of the fin rays. Ural region deformities were also frequent in the separately investigated populations.The current results indicate that Rainbow Trout are not able to maintain normal bone development under current farming conditions, consequently, jeopardizing the welfare of the fish.

Early intervention of unerupted maxillary central incisor: A case series

Early intervention of an impacted maxillary central incisor is crucial to avoid space loss with tipping of the adjacent teeth and allows normal root development. This case series demonstrates the clinical considerations of a surgical-orthodontic approach in managing this eruption anomaly and its challenges. All three cases involved young patients aged 7–9 years with an impacted upper left central incisor and a positive history of dental trauma. An upper sectional fixed appliance was bonded to facilitate the closed eruption of the impacted central incisor. The treatment duration increases when more space is required for the impacted tooth. There was a marginal gingival discrepancy of all the treated central incisors with vertical relapse seen upon review, indicating the need for a careful surgical approach with good hygiene maintenance and a bonded retainer as retention. Early referral for the management of an impacted maxillary central incisor through a surgical-orthodontic approach is often successful, but treatment risks, duration, and retention regimen should be discussed with the parents for informed consent.

7308 A Case of Thyroid Hormone Resistance Associated With a Novel Mutation in the THRA Gene

Abstract Disclosure: J.A. Siddiqui: None. M. Barbosa: None. V. Fettig: None. C.J. Romero: None. Introduction: Thyroid hormone resistance (THR) is a syndrome leading to decreased response of target organs to thyroid hormone. Normal thyroid hormone action is mediated by thyroid hormone nuclear receptors and is essential for normal development and metabolism. Two isoforms are encoded by the thyroid hormone receptor α and β genes (THRA and THRB). Mutations in THRB are commonly reported with limited cases of THRA mutations. We report a 15-month-old and her mother with a pathogenic variant in the THRα receptor leading to thyroid hormone resistance. CASE: A 15-month-old ex-39-week gestation female was born small for gestational age (birth weight: 2450 grams,3rd %ile and birth length: 17 inches,1st %ile). The newborn screen was normal. She presented with macroglossia, low tone and global developmental delay. She had severe constipation complicated by rectal prolapse that required surgical correction. There are multiple relatives (mother, maternal half-brother and maternal grandparents) with neurodevelopmental issues. The mother’s previous genetic evaluation was non-diagnostic. Mother reports a thyroid condition but without treatment. The patient was initially referred to genetics and whole exome sequencing revealed a heterozygous c.1205 T&amp;gt;C p. (L402P) variant in the THRα gene, which was maternally inherited and reported as a variant of uncertain significance. On physical exam, Heart rate was 112 bpm; height &amp;lt;1%ile (Z-score -3.22 SD), weight 3%ile (Z-score -1.89 SD). Patient has a wide anterior fontanelle (4x3 cm), macroglossia and delayed teeth eruption. Other exam findings: non-palpable thyroid and postaxial polydactyly on the 5th digit of the right toe. Thyroid hormone testing: normal TSH 1.829 uIU/mL, low total T4 4.4 mcg/dL, low Free T4 of 0.58 ng/dL and high free T3 of 4.24 pg/mL. Levothyroxine treatment was initiated(25 mcg daily). After 1 month treatment, TSH level was 0.23 uIU/mL, total T4 was 6.1 mcg/dL and low reverse T3 of 5.8 ng/dL. DISCUSSION: Thyroid hormone resistance due to THRα mutations are rare and under-recognized. The main clinical phenotype includes growth retardation, delayed development, decreased muscle tone, delayed tooth eruption and constipation. Unlike patients with THRβ mutations, the hypothalamus-pituitary-thyroid axis in patients with THRα mutations is minimally affected with a normal TSH level. Total T3 levels are elevated with slightly low total T4 and free T4:T3 ratio is low. Treatment with levothyroxine leads to suppressions of TSH levels, therefore confirming intact central T3 feedback loop. Reports, however, show minor clinical improvements with treatment; therefore further research is needed in these patients to explore more effective therapeutic options. We present a case of a novel congenital THRA mutation leading to a clinical phenotype consistent with THR. She continues care in our clinic with hopes to further study her mutation. Presentation: 6/2/2024

Regression of microcephaly as a protective factor of neuropsychomotor development in fetal surgery for occipital encephalocele.

Encephaloceles are neural tube closure defects characterized by herniation of intracranial contents through the skull, with a mortality rate of 33.3%. Approximately 50% of patients who survived have some degree of neuropsychomotor developmental impairment or seizures. This study aimed to analyze the relationship between good neuropsychomotor development (NPMD) in patients undergoing fetal occipital encephalocele correction and the reversal of microcephaly, comparing these outcomes with those observed in patients who underwent postnatal surgery. The 22 participants were categorized into two groups: 10 in the fetal group (FG) and 12 in the postnatal group (PNG). During the study, 1 patient was excluded from the FG and 2 patients were excluded from the PNG, totaling 19 patients in the study. All patients were diagnosed, evaluated, and monitored by the same healthcare service between July 2012 and July 2018. All participants were subjected to a careful developmental assessment using the Bayley Scale of Infant Development, Second Edition (BSID-II), up to 2years and 11months of age. Additionally, CP measurements were taken during the first year of life to monitor their progress. The relationship between microcephaly reversal and NPMD was studied. The CP adjusted for gestational age showed a tendency toward the reversal of progressive microcephaly after correction of encephaloceles in the FG. We found a statistically significant difference in the median BSID-II score between the PNG and FG. Patients in the FG maintained normal CP development in the first year of life, whereas those in the PNG remained microcephalic. The reversal of microcephaly in the FG directly influences good NPMD and can be considered a protective factor.

Geography, altitude, agriculture and hypoxia.

Reduced oxygen availability (hypoxia) represents a key plant abiotic stress in natural and agricultural systems, but conversely it is also an important component of normal growth and development. We review recent advances that demonstrate how genetic adaptations associated with hypoxia impact the known plant oxygen sensing mechanism through the PLANT CYSTEINE OXIDASE (PCO) N-degron pathway. Only three protein substrates of this pathway have been identified, and all adaptations identified to date are associated with the most important of these, the group VII ETHYLENE RESPONSE FACTOR transcription factors (ERFVIIs). We discuss how geography, altitude, and agriculture have all shaped molecular responses to hypoxia, and how these responses have emerged at different taxonomic levels through the evolution of land plants. Understanding how ecological and agricultural genetic variation acts positively to enhance hypoxia tolerance will provide novel tools and concepts to improve the performance of crops in the face of increasing extreme flooding events.

Стандартизация методики «Перцептивное моделирование» для детей 5-6 и 6-7 лет

&lt;p&gt;In modern sociocultural conditions, reliable diagnostic tools are needed to assess the mental development of a child, which would at the same time make it possible to adjust the objectives of educational work. The article reflects the results of adaptation and standardization of the "Perceptual modeling" test included in the diagnostic set for assessing the mental development of preschoolers (L.A. Wenger and colleagues). The study sample consisted of two groups: children 5-6 (N=1003) and children 6-7 (N=1516) years old. In these groups, children were offered various test options based on their age-related perceptual modeling capabilities. The adaptation of the "Perceptual modeling" test involved converting it into electronic form, changing the system for evaluating the results obtained and statistically verifying the possibility of using it in this form to solve diagnostic problems. The test standardization procedure has shown good external and internal validity, and its diagnostic reliability. Statistical analysis revealed the absence of significant gender differences in the performance of the test and the presence of significant differences between children with normal development and children with disabilities (speech, hearing impairment and mental retardation). As a result of standardization, age norms for mastering perceptual modeling actions for children with normal development and children with disabilities were determined by children of the sixth and seventh years of life.&lt;/p&gt;

Impacts of Different Perinatal Factors on Faecal Immune Compounds in Infants: Determination of Normal Values

The gut microbiota is a key and primary stimulus for the development of a host’s immune system. The early establishment of the gut microbiota is affected by several perinatal factors but little is known about their influence on shaping normal immune development and, consequently, on the programming of future health. The analysis of different immune compounds is well-documented in serum samples; however, their presence in faecal samples has not been studied, and this information could be valuable in early life. In this context, the authors of this study aimed to both describe the immunological faecal profile of a cohort of one-month-old infants and describe the impact of different perinatal factors, exploring possible associations between immune compounds and gut microbiota in faecal samples. Clear differences in immune profile were observed between full-term and premature infants. Breastfeeding increases IgG2, IgG4, and IgA; in addition, male babies showed some increased Igs, among other observations. Overall, the findings of this study reinforce the hypothesis that microorganisms and immune compounds interact with each other in the early neonatal gut and that understanding these interactions in depth will help us comprehend the influence of the gut microbiota on short- and long-term infant health outcomes.

Evaluating T1-weighted MRI techniques for fetal gastrointestinal diagnostics: A comparative study

PurposeIn clinical practice, fetal gastrointestinal magnetic resonance imaging (MRI) encounters significant challenges. T1-weighted images are particularly susceptible to the effects of fetal and maternal movements compared to other weighted images, complicating the acquisition of satisfactory results. This study aimed to compare three fast 3D-T1 weighted gradient echo (GRE) sequences—free-breathing stack-of-stars VIBE (STAR-VIBE), breath-hold VIBE (BH-VIBE), and free-breathing multi-average VIBE (MA-VIBE)—for fetal gastrointestinal MRI in fetuses with both normal and abnormal gastrointestinal tracts between 21 and 36 weeks of gestation. MethodsThis study enrolled 67 pregnant women who underwent fetal abdominal MRI at our hospital between October 2022 and October 2023, during their gestational period of 21–36 weeks. Among these participants, 22 were suspected of having fetal gastrointestinal anomalies based on ultrasound findings, while the remaining 45 were considered to have normal fetal gastrointestinal development. All subjects underwent True fast imaging with steady-state precession sequence scanning along with three T1-weighted imaging techniques on a Siemens 1.5-T Aera scanner: STAR-VIBE, BH-VIBE, and MA-VIBE. Two radiologists evaluated image quality, intestinal clarity, and lesion conspicuity using a five-point scale where higher scores indicated superior performance for each technique; they were blinded to the acquisition schemes used. Interobserver variability assessments were also conducted. ResultsThe free-breathing MA-VIBE sequence demonstrated significantly better performance than both STAR-VIBE and BH-VIBE in terms of fetal gastrointestinal MRI quality (3.81 ± 0.40 vs. 3.35 ± 0.70 vs. 2.90 ± 0.64; p < .05). The STAR-VIBE and BH-VIBE sequences exhibited moderate consistency (kappa = 0.586 and kappa = 0.527 respectively; P < .05), whereas the MA-VIBE sequence showed higher consistency (kappa = 0.712; P < .05). ConclusionThe free-breathing MA-VIBE sequence provided superior visualization for assessing fetal intestinal conditions compared to other methods employed in this study. On a 1.5 T MRI device, T1-weighted images based on the free-breathing MA-VIBE sequence can effectively overcome motion artifacts and compensate for the reduced signal-to-noise ratio caused by the application of acceleration techniques, thus significantly improving the quality of T1-weighted images.

Prenatal ultrasound detection of fetal amniotic band ingestion in monochorionic diamniotic twin pregnancy: a rare case report

BackgroundAmniotic Band Syndrome (ABS) is a rare congenital condition characterized by the formation of fibrous bands within the amniotic sac that can entangle and restrict fetal development, leading to various deformities. In this report, we present an unprecedented case of fetal amniotic band ingestion in a monochorionic diamniotic (MCDA) twin pregnancy. Reporting this case is essential for expanding the understanding of the diverse presentations of amniotic bands, considering this rare entity in the differential diagnosis of prenatal ultrasound findings, and emphasizing the importance of vigilant prenatal monitoring and individualized management strategies.Case PresentationA 35-year-old gravida 2, para 1 woman with an MCDA twin pregnancy experienced an uneventful pregnancy until the 33rd week, when routine ultrasonography revealed mild intrauterine growth restriction in both twins. At 35 weeks and 5 days gestation, the patient presented with mild abdominal pain. An emergency ultrasound revealed that Twin A ingested an amniotic band. Despite the absence of overt fetal distress, a comprehensive risk assessment was conducted, taking into account potential complications, such as airway obstruction and gastrointestinal issues due to prolonged amniotic band ingestion. Considering the risks versus the benefits of continued gestation and the near-term status, an emergency cesarean section was performed. The procedure resulted in the successful delivery of both twins with satisfactory Apgar scores. A 9-cm fibrous strand was promptly extracted from Twin A’s oral cavity after delivery, confirming prenatal diagnosis. Both neonates underwent thorough examinations, revealing no additional anomalies, and demonstrated normal development during the nine-month follow-up.ConclusionThis case highlights the inherent challenges in diagnosing and managing the rare presentations of amniotic band-related complications, particularly in MCDA twin pregnancies. The instance of fetal amniotic band ingestion underscores the vital role of comprehensive prenatal imaging in ensuring accurate diagnosis and tailoring individualized risk assessments throughout the pregnancy in such rare and complex situations.

Application of Gene Expression Microarray for the Classification of Ph-Like B-Cell Acute Lymphoblastic Leukemia.

Ph-like ALL has gene expression profile similar to Ph-positive ALL but without the BCR::ABL1 fusion. The disease presents higher rates of severe clinical features and is associated with unfavorable outcomes. There is still no standard pipeline for molecular characterization of the disease, and no valid predictor gene panel is available worldwide. We performed expression microarray on 25 B-cell ALL and 6 Ph-positive B-cell ALL to cluster and identify the transcriptional signature of Ph-like ALL. qRT-PCR was used to confirm the expression of candidate genes. Four out of 25 samples (16%) shared gene expression signatures related to and clustered with control Ph-positive samples. Analysis of genes differentially expressed in Ph-like B-cell ALL and evidentially functional in normal blood cell development and leukemogenesis, we selected genes as potential biomarkers for Ph-like B-cell ALL in our dataset: ADGRE2, CD9, EPHA7, FAM129C, TCL1A, and VPREB1. Those genes were filtered by Ph-like gene signatures obtained from distinct reliable data, resulting in five genes, CA6, CHN2, JAK1, JCHAIN, and PON2, selected for validation by qRT-PCR. The Ct values of genes, including CA6 (p = 0.0017), PON2 (p = 0.0210), TCL1A (p = 0.0064), and VPREB1 (p = 0.0338), were significant in Ph-like ALL. GSEA analysis identified VPREB1 as enrichment in the KRAS signaling pathway, and several genes that interact with VPREB1 were reported as critical molecules involved in the leukemogenesis of B-cell ALL. In summary, we demonstrate using a gene expression microarray for classifying Ph-like B-cell ALL and highlight VPREB1 as a potential biomarker for this disease.

Mental Health in Education for Crisis-affected Preschool Children: Multilevel Monitoring

Introduction: The crisis in Ukraine, related to military actions, poses a significant threat to the mental health of preschool children due to their vulnerability, limited self-awareness, and perception of their surroundings, as well as the critical developmental phase characterized by the establishment of foundational personality structures. Chronic stress and trauma can disrupt normal brain development, potentially leading to delays in cognitive and emotional development in the long term. Therefore, it is essential to systematically identify and analyze the negative factors affecting the mental development of preschool children across key domains, contributing to educational deficits and developmental gaps, and to design targeted interventions to solve those emerging issues. Purpose: The study is focused on the development and implementation of strategies for supporting, preserving, and enhancing the mental well-being of preschool children residing in areas proximate to armed conflict. The research underscores the importance of early and systematic monitoring across various levels (including children, families, educators, professional associations, and early childhood education institutions, including those with alternative forms of preschool education designed to accommodate crisis conditions). Methodology: Multilevel monitoring has encompassed 3,843 children situated in conditions detrimental to their mental health and development across seven frontline regions of Ukraine (Dnipropetrovsk, Donetsk, Zaporizhzhia, Mykolaiv, Odesa, Sumy, Kharkiv). This initiative is a part of a project by "All-Ukrainian Public Organization 'Association of Early Childhood Education Professionals'", with informational support from the Ministry of Education and Science of Ukraine and is being implemented in collaboration with the United Nations (UNICEF) project "Improving Access to Early Childhood Education Services in Emergencies and Early Recovery in Ukraine." Level 1 - initial, intermediate, and summative monitoring involved establishing the baseline developmental level of senior preschool children and identifying gaps across key areas, with subsequent measurement of progress and its correlation with interventions aimed at supporting and maintaining children’s mental health. Measurement of indicators was expressed through their manifestation at the minimum and maximum points for each child, with the establishment of an average score (average score = sum of all individual scores divided by the number of children). The average score reflects the overall performance between the lowest and highest indicators across children, educators, regions, and nationally. This analysis was conducted using a web-based spreadsheet program, Google Sheets, which is part of the Google Drive office suite." Level 2 - organizational and methodological monitoring focused on evaluating the methodological and organizational aspects of the educational process as fundamental factors in preventing negative impacts on children’s mental health. This was conducted using an electronic form developed in Google Forms, utilizing the Google Sheets web-based spreadsheet program, which is part of the Google Drive office suite. Level 3 - monitoring the quality of the educational process in early childhood education institutions using the ECERS-3 methodology, which allows for the analysis of comfort levels, developmental conditions, safety, and support for the mental health of preschool children. This involves an electronic Google Form equivalent to the paper-based ECERS-3 assessment; automatic calculations are performed according to the formulas specified by the international ECERS-3 methodology (Harms et al., 2020). Results: The study of the development of senior preschool children, based on the analysis of key domains through regular psychological and pedagogical observations and the use of diagnostic tools over a period of five months, enabled the identification of early signs of stress, anxiety, and other emotional manifestations. This assessment facilitated the evaluation of children's mental health and the development of a system of effective interventions to address the identified issues. Conclusion: The study underscores the importance of identifying personal characteristics of senior preschool children and developmental gaps across key domains to organize interventions and support measures aimed at preserving mental health, ensuring comprehensive development, and mitigating negative factors in crisis conditions. The results of the multilevel monitoring are valuable for updating educational practices and adapting them to crisis situations. Addressing the identified educational losses and gaps, including those related to social-emotional development and stress resilience, allows for the development of structured programs to counteract negative impacts and facilitate the recovery of preschool children

Cross-fused Ectopic Kidney in a Term Neonate

We report on a term neonate with a birthweight of 2300g antenatally suspected to have an absent left kidney. Postnatally the right kidney was palpable, and ultrasound confirmed an enlarged right kidney with obstruction at the pelvic-ureteric junction and multiple renal cysts. The left kidney had an unusual appearance with its upper pole cross-fused with the lower pole of the left kidney suggestive of a cross-fused kidney, with the ureter of the crossfused kidney joining the bladder on the left side. The cross-fused kidney also showed pelvicalyceal dilatation and cystic changes’ and DMSA scans confirmed the non-functioning of the crossfused kidney with a normally functioning right kidney. MCU was normal. The neonate remained hemodynamically stable throughout the NICU stay with normal blood pressure and renal function tests. He is currently 6 months old and on regular follow-up with normal growth development. We describe the approach and management of this rare condition of crossfused kidney.