Histotoxicity induced by copper oxide nanoparticles (CuO-NPs) on developing mice (Mus musculus).

The wide range of applications of nanoparticles (NPs) in various industries have led to serious consequences in terms of teratogenic toxicity. The aim of current work was to evaluate the teratogenic effects of copper oxide (CuO) nanoparticles in albino mice.In this experimental study, after mating, inseminated 40 female mice were divided randomly into 4 pools (1 control and 3 experimental), ten each. Doses were administered intravenously (We followed the protocol by Yaqub et al. (2018), intravenous application is faster route as compared to oral dosage)to all the experimental groups on the 6th day of gestation (GD), dose concentrations were 200, 133.3 and 100 mg/kg body weights respectively.The doses were prepared in sequence (1/2, 1/3, 1/4 0f LD50) according to already published work. The effects of CuO-NPs show linear relationship with the above sequence. The control group was administered only with distilled water.The gravid females were sacrificed through cervical disruption at the 18th day of gestation, fetuses were removed and divided into four sets (pools) for morphometric, morphological and histological studies. Data were subjected to statistical analysis by using Tukey's test in light of ANOVA at p < 0.05 level of significance. Findings of the present study showed that CuO-NPs various concentrations affect developmental abnormalities i.e.runt embryos, resorbed uteri, exencephaly, hygroma, macroglossia, micromelia, open eye, omphalocoel, scoliosis, kyphosis and kinked tail. It is concluded that exposure to CuO-NPs may potentially lead to the developmental deformities in mice.

Three-Dimensional Evaluation of Bifid Condyle by Cone-Beam Computed Tomography.

Bifid condyle is a rare developmental anomaly that results from an obstructed blood supply during its development. Bifid condyle is more often unilateral, although bilateral. A case of a bifid condyle is evaluated three-dimensionally in three orthogonal planes namely coronal, sagittal and axial sections. The etiology, clinical features, diagnostic, non-surgical and surgical treatment modalities of bifid condyle are discussed.

Imaging of congenital and developmental cystic lesions of the brain: a narrative review.

INTRODUCTION: Congenital and developmental intracranial cysts represent a large heterogenous group with varied presentations and etiologies. They can range from normal variants to pathologic lesions often associated with known congenital syndromes or acquired insults. While some are incidentally found, others are symptomatic or may become symptomatic over time. The preferred type of neuroimaging for timely diagnosis helps determine appropriate management and treatment, if indicated. AREAS COVERED: In this narrative review article, authors present a comprehensive description of developmental cystic lesions. Imaging descriptions are provided for each type of cystic lesion as well as several representative images. EXPERT OPINION: As advanced neuroimaging techniques become more ubiquitous in clinical use, more light may be shed on the natural history of certain intracranial cystic lesions throughout the lifespan. This includes prenatal imaging for early identification and prognostication to surveillance imaging into advanced age to ascertain associations of certain cystic lesions with age-related cognitive dysfunction.

Assessing the toxicity of aegerolysin-based bioinsecticidal complexes using the sea urchin Paracentrotus lividus as model organism.

The use of alternative solutions for pest management to replace pesticides in agriculture is of great interest. Proteinaceous complexes deriving from edible oyster mushrooms were recently proposed as environmentally friendly bioinsecticides. Such complexes, composed of ostreolysin A6 (OlyA6) and pleurotolysin B (PlyB), target invertebrate-specific membrane sphingolipids in insect's midgut, causing death through the formation of transmembrane pores. In this work, the potential impact of OlyA6/PlyB complexes was tested in the Mediterranean sea urchin Paracentrotus lividus, as an indicator of environmental quality. The ability of the fluorescently tagged OlyA6 to bind sea urchin gametes (sperm, eggs), the lipidome of sea urchin gametes, and the potential toxic effects and developmental anomalies caused by OlyA6/PlyB complexes on P. lividus early development (embryo, larvae) were investigated. The binding of the fluorescently tagged OlyA6 could be observed only in sea urchin eggs, which harbor OlyA6 sphingolipid membrane receptors, conversely to sperm. High protein concentrations affected sea urchin fertilization (>750 µg/L) and early development (> 375 µg/L in embryos; >100 µg/L in larvae), by causing toxicity and morphological anomalies in embryos and larvae. The main anomalies consisted in delayed embryos and incorrect migration of the primary mesenchyme cells that caused larval skeletal anomalies. The classification of these anomalies indicated a slight environmental impact of OlyA6/PlyB complexes at concentrations higher than 750 µg/L. Such impact should not persist in the marine environment, due to the reversible anomalies observed in sea urchin embryos and larvae that may promote defense strategies. However, before promoting the use of OlyA6/PlyB complexes as bio-pesticides at low concentrations, further studies on other marine coastal species are needed.

Appendage abnormalities in spiders induced by an alternating temperature protocol in the context of recent advances in molecular spider embryology.

In the literature there are numerous reports of developmental deformities in arthropods collected in their natural habitat. Since such teratogenically affected individuals are found purely by chance, the causes of their defects are unknown. Numerous potential physical, mechanical, chemical, and biological teratogens have been considered and tested in the laboratory. Thermal shocks, frequently used in teratological research on the spider Eratigena atrica, have led to deformities on both the prosoma and the opisthosoma. In the 2020/2021 breeding season, by applying alternating temperatures (14 °C and 32 °C, changed every 12 h) for the first 10 days of embryonic development, we obtained 212 postembryos (out of 3,007) with the following anomalies: oligomely, heterosymely, bicephaly, schistomely, symely, polymely, complex anomalies, and others. From these we selected six spiders with defects on the prosoma and two with short appendages on the pedicel for further consideration. The latter cases seem particularly interesting because appendages do not normally develop on this body part, viewed as the first segment of the opisthosoma, and appear to represent examples of atavism. In view of the ongoing development of molecular techniques and recent research on developmental mechanisms in spiders, we believe the observed phenotypes may result, at least in part, from the erroneous suppression or expression of segmentation or appendage patterning genes. We consider "knockdown" experiments described in the literature as a means for generating hypotheses about the sources of temperature-induced body abnormalities in E. atrica.

Pregnancy, infection, and epigenetic regulation: A complex scenario.

A unique immunological condition, pregnancy ensures fetus from maternal rejection, allows adequate fetal development, and protects against microorganisms. Infections during pregnancy may lead to devastating consequences for pregnant women and fetuses, resulting in the mother's death, miscarriage, premature childbirth, or neonate with congenital infection and severe diseases and defects. Epigenetic (heritable changes in gene expression) mechanisms like DNA methylation, chromatin modification, and gene expression modulation during gestation are linked with the number of defects in the fetus and adolescents. The feto-maternal crosstalk for fetal survival during the entire gestational stages are tightly regulated by various cellular pathways, including epigenetic mechanisms that respond to both internal as well outer environmental factors, which can influence the fetal development across the gestational stages. Due to the intense physiological, endocrinological, and immunological changes, pregnant women are more susceptible to bacterial, viral, parasitic, and fungal infections than the general population. Microbial infections with viruses (LCMV, SARS-CoV, MERS-CoV, and SARS-CoV-2) and bacteria (Clostridium perfringens, Coxiella burnetii, Listeria monocytogenes, Salmonella enteritidis) further increase the risk to maternal and fetal life and developmental outcome. If the infections remain untreated, the possibility of maternal and fetal death exists. This article focused on the severity and susceptibility to infections caused by Salmonella, Listeria, LCMV, and SARS-CoV-2 during pregnancy and their impact on maternal health and the fetus. How epigenetic regulation during pregnancy plays a vital role in deciding the fetus's developmental outcome under various conditions, including infection and other stress. A better understanding of the host-pathogen interaction, the characterization of the maternal immune system, and the epigenetic regulations during pregnancy may help protect the mother and fetus from infection-mediated outcomes.

Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis.

Introduction: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Retrospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories. Patients and methods: We applied a reanalysis strategy based on intensive prospective bibliographic monitoring along with direct application of the GREP command-line tool (to "globally search for a regular expression and print matching lines") in a large ES database. For 18 months, we submitted the same five keywords of interest [(intellectual disability, (neuro)developmental delay, and (neuro)developmental disorder)] to PubMed on a daily basis to identify recently published novel disease-gene associations or new phenotypes in genes already implicated in human pathology. We used the Linux GREP tool and an in-house script to collect all variants of these genes from our 5,459 exome database. Results: After GREP queries and variant filtration, we identified 128 genes of interest and collected 56 candidate variants from 53 individuals. We confirmed causal diagnosis for 19/128 genes (15%) in 21 individuals and identified variants of unknown significance for 19/128 genes (15%) in 23 individuals. Altogether, GREP queries for only 128 genes over a period of 18 months permitted a causal diagnosis to be established in 21/2875 undiagnosed affected probands (0.7%). Conclusion: The GREP query strategy is efficient and less tedious than complete periodic reanalysis. It is an interesting reanalysis strategy to improve diagnosis.

Ciliated foregut cyst of the gall bladder in the Calot's triangle: A case report with review of literature.

Ciliated foregut cysts (CFCs) are rare anomalies of the foregut epithelium. The common sites in the abdomen are liver and gall bladder. There are only 16 cases of CFC reported in the gall bladder to date. A 20-year-old girl presented with pain in the right upper abdomen. There was a radiological evidence of cystic lesion in the region of Calot's triangle. A differential diagnosis of either type 2 choledochal cyst or CFC was made. Intraoperative and histopathological findings were suggestive of CFC. CFC should be kept in mind as a rare differential diagnosis when evaluating cysts in the gall bladder fossa.

Research progress on ankylosis of primary molars / 口腔疾病防治

@#Ankylosis of primary molars is a kind of eruption abnormality of the teeth, where the periodontal membrane disappears, owing to a bony union between bone and root. Studies have shown that the common proportion of ankylosed primary molars is 1.3%~8.9% with an equal occurrence. In the primary dentition, the mandibular first primary molar is the most commonly affected tooth, while in the middle mixed dentition stage of development, the second primary molar is more affected. Its etiology may be related to genetics, signaling pathways of mineralization metabolism of local alveolar bone or cementum, cytokines secreted by epithelial rest cells of Malassez, and enhanced inflammatory reactions during physiological absorption of roots. Ankylosis of primary molars can be diagnosed by clinical symptoms and imaging and is classified as mild, moderate and severe according to the degree of infraocclusion. As it may cause a series of complications, such as occlusal disturbances, delayed exfoliation and incomplete alveolar process development, multidisciplinary treatment, including in the departments of pediatric dentistry, orthodontics, periodontics and prosthodontics, should be adopted, and long-term treatment is determined based on the patient's age, severity of infraocclusion, and presence of permanent teeth. This review summarizes the etiology, diagnosis, complications and treatment of ankylosed primary molars to provide a reference for the clinical diagnosis and treatment of decidual molar fixation.

Resin Infiltration of Non-Cavitated Enamel Lesions in Paediatric Dentistry: A Narrative Review.

The resin infiltration (RI) technique was introduced as one of the minimal intervention dentistry strategies in addressing dental caries among the paediatric population. This technique used the low-viscosity resin monomer to infiltrate the non-cavitated carious lesion and other developmental enamel porosities, thus allowing the conservation of the tooth structure. This narrative review aims to explore the value of RI in Paediatric Dentistry. Through our search of the literature, the development of the material, their clinical applications and shortcomings, as well as the innovation that has been carried out to improve the current RI, were discussed. There are number of high-level evidence supporting the use of RI in arresting non-cavitated proximal caries lesions in primary and permanent teeth, but its efficacy in managing anterior white spot lesions is still unclear. Limited penetration depth, not radiopaque and questionable long-term colour and material stability were among the limitation of the material. Various laboratory-based studies have been conducted to improve the current properties of RI. Nevertheless, RI has emerged as one of the important micro-invasive techniques in addressing non-cavitated and anterior white-spot enamel lesions in children and adolescents with great success.

Epidemiological, Clinical and Radiographic Features of Supernumerary Teeth in Nonsyndromic Bosnian and Herzegovinian Population: a Monocentric Study.

Background: Supernumerary teeth (ST) represent one of the most common developmental anomalies among humans. Objective: In this study, we set a goal to investigate ST prevalence in the Bosnian and Herzegovinian population along with characteristics and complications that ST can cause. Methods: This retrospective study was based on panoramic radiographs, CBCT images, and dental records. Analyzed ST characteristics were: type, morphology, location, eruption state, location in the arch, orientation, and associated clinical complications. Statistical analysis included univariate analysis and bivariate analysis using Fisher's exact test with a confidence interval of 95% (p<0.05). Results: On a sample of 10.237 patients, ST teeth appear in 100 patients with a prevalence of 0.98%. Out of 138 analyzed ST mesiodens was the most frequent (43.47%). The most common location of the ST was maxilla (77.53%). The majority of ST were impacted (90.5%) but with no complications (71.7%). There was statistically significant relationship (p<0.001) between the type of ST and location (mesiodens and distomolars were mostly found in the maxilla). The relationship between ST type and morphology was also statistically significant (p<0.001)-mesiodens was associated with conical morphology, parapremolar with supplementary, and distomolar with tuberculate morphology. The occurrence of ST-associated retention of adjacent teeth was correlated to the type of tooth (p<0.001). Conclusion: The present study found prevalence of ST in B&H population to be low. Although associated pathology was not high early diagnosis allows optimal patient management which reduces later complications.

Morphological Diversity of Permanent Maxillary Lateral Incisors and Their Impact on Aesthetics and Function in Orthodontically Treated Patients.

The aim of this study was to determine the frequency of different crown shapes and associated dental anomalies of the permanent maxillary lateral incisor (PMLI) and their impact on aesthetics and occlusion (function) in orthodontically treated patients. Materials and Methods: The records of 372 subjects, which consisting of study casts, panoramic radiographs and anamnestic data, were investigated for crown shape and associated dental anomalies of PMLI and potential dental treatment to achieve satisfactory aesthetics and function. Descriptive statistics, including means, standard deviations and percentages for the observed variables, were calculated. Data were analyzed using the chi-square test. p-Values < 0.05 were considered as statistically significant. Results: The results showed that the most common crown shapes of PMLI were trapezoidal-shaped (59.8%), followed by central incisor-shaped (26.7%), canine-shaped (11.2%) and peg-shaped (2.3%), without statistically significant difference between genders. Developmental anomalies were found in 86 (11.6%) PMLI. All subjects with developmental anomalies were included in orthodontic treatment, and 91.2% of them need interdisciplinary treatment to achieve satisfactory aesthetics and function. Conclusions: The morphological diversity and developmental anomalies of the PMLI may affect aesthetics and function and should be considered in treatment planning.

Developmental Anomalies of the Inferior Vena Cava and its Tributaries: What the Radiologist Needs to Know?

Inferior vena cava (IVC) can be involved by a wide gamut of developmental anomalies owing to its complex embryogenesis. Developmental anomalies of the IVC are not infrequent, seen in approximately 8.7% of the general population. Although most of the anatomical variations are asymptomatic, identification of these variations is important before planning any vascular surgery or interventional procedure in relation to the IVC to avoid inadvertent complications. Conventional venography has largely been replaced by noninvasive cross-sectional imaging modalities for detecting IVC abnormalities. Ultrasonography, often used for initial evaluation, is highly operator-dependent and the infrarenal part of IVC is often obscured by bowel gases. While magnetic resonance imaging is devoid of radiation risks, its use is limited due to limited availability and the frequent need for sedation. Computed tomography (CT) venography plays a pivotal role in the detection of these anomalies as it has an excellent spatial resolution along with availability of multiple postprocessing tools such as multiplanar reconstruction with generation of maximum intensity projection and volume-rendered images. This pictorial review focuses on the embryogenesis of IVC, various developmental anomalies of the IVC and its tributaries, their appearance on CT venography and conceivable clinical relevance.

Update on pediatric corneal diseases and keratoplasty.

Managing pediatric corneal disorders is challenging as the prognosis of pediatric keratoplasty depends on several factors. Advancements in the genetic basis of congenital corneal diseases and investigations in congenital corneal conditions provide a better understanding of pediatric corneal conditions. Surgeons performing keratoplasty in children now have a choice of various techniques. Evolving surgical techniques of anterior lamellar and endothelial keratoplasties have expanded the management interventions in these pediatric corneal morbidity conditions; however, considerable concerns still exist in association with corneal transplantation in infants and children. Outcomes in pediatric keratoplasty depend upon the preoperative indications, the timing of surgical intervention, intraoperative and postoperative factors including the patient/care givers' compliance. Factors such as low scleral rigidity, higher rate of graft failure, need for frequent examinations under anesthesia, and difficulty in optimal visual acuity assessment still remain a considerable challenge in pediatric scenarios. In children, deprivation amblyopia as a result of the corneal opacification can adversely affect visual development, causing dense amblyopia. Outcomes to surgical interventions for management of corneal opacification in children are further compromised by the preexisting amblyopia apart from the concerns of refractive outcome of the graft. Graft rejection, graft infection, amblyopia, and glaucoma continue to be serious concerns. In recent years both anterior and posterior lamellar keratoplasty techniques are being increasingly performed in pediatric eyes, which offer advantages in the form of lower risk of graft rejection. The timing of surgery, careful case selection, cautious intraoperative approach, and optimal postoperative management can improve the anatomical and functional outcome in difficult cases.

Allan-Herndon-Dudley Syndrome: A Novel Pathogenic Variant of the SLC16A2 gene.

Allan-Herndon-Dudley syndrome (AHDS) is a rare disorder characterized by thyroid irregularities, neurological issues, and developmental delay. In this article, we reported a patient with AHDS who presented with severe developmental delay and failure to thrive in the setting of thyroid irregularities. The patient had missense mutations in the SLC16A2 gene, which codes for monocarboxylate transporter 8 (MCT8). We identified two single-nucleotide variants, including guanine to alanine substitution at position +1 of intron 5 (IVS5+1 G>A) and guanine to alanine substitution at position 1400 of intron 1 (c.1400G>A). This variant has not been previously reported as pathogenic in a patient diagnosed with AHDS, as missense and in-frame single amino-acid deletions have not generally been associated with severe neurodevelopment sequela. We review the clinical and laboratory findings of this rare condition. We will discuss the value of early recognition and diagnosis based on promising clinical trials to treat the neurological and developmental sequela associated with AHDS.

Interference with zinc homeostasis and oxidative stress induction as probable mechanisms for cadmium-induced embryo-toxicity in zebrafish.

The present study was conducted to provide new insights into the mechanisms that may be responsible for cadmium (Cd)-induced toxicity in zebrafish larvae as well as the role of the trace element zinc (Zn) in reversing Cd harmful effects. For this purpose, zebrafish eggs were exposed to Cd or/and Zn for 96 h. The effects on morphological aspect; mortality rate; Cd, Zn, and metallothionein (MT) levels; oxidative stress biomarkers; as well as molecular expression of some genes involved in Zn metabolism (Zn-MT, ZIP10, and ZnT1) and in antioxidant defense system (Cu/Zn-SOD, CAT and GPx) were examined. Our results showed that Cd toxicity was exerted, initially, by an interference with Zn metabolism. Thus, Cd was able to modify the expression of the corresponding genes so as to ensure its intracellular accumulation at the expense of Zn, causing its depletion. An oxidative stress was then generated, representing the second mode of Cd action which resulted in developmental anomalies and subsequently mortality. Interestingly, significant corrections have been noted following Zn supplementation based, essentially, on its ability to interact with the toxic metal. The increases of Zn bioavailability, the improvement of the oxidative status, as well as changes in Zn transporter expression profile are part of the protection mechanisms. The decrease of Cd-induced MTs after Zn supplement, both at the protein and the mRNA level, suggests that the protection provided by Zn is ensured through mechanisms not involving MT expression but which rather depend on the oxidative status.

Monsters reveal patterns: bifurcated annelids and their implications for the study of development and evolution.

During recent decades, the study of anatomical anomalies has been of great relevance for research on development and its evolution. Yet most animal groups have never been studied under this perspective. In annelids, one of the most common and remarkable anomalies is anteroposterior axis bifurcation, that is animals that have two or more heads and/or tails. Bifurcated annelids were first described in the 18th century and have been occasionally reported since then. However, these animals have rarely been considered other than curiosities, one-off anomalies, or monsters, and a condensed but comprehensive analysis of this phenomenon is lacking. Such an analysis of the existing knowledge is necessary for addressing the different patterns of annelid bifurcation, as well as to understand possible developmental mechanisms behind them and their evolution. In this review we summarize reports of annelid bifurcation published during the last 275 years and the wide variety of anatomies they present. Our survey reveals bifurcation as a widespread phenomenon found all over the annelid tree. Moreover, it also shows that bifurcations can be classified into different types according to anatomy (lateral versus dorsoventral) or developmental origin (embryonic versus postembryonic, the latter occurring in relation to regeneration, reproduction, or growth). Regarding embryos, three different types of bifurcation can be found: conjoined twins (in clitellates); Janus embryos (two posterior ends with a single head which shows duplicated structures); and duplicitas cruciata embryos (with anterior and posterior bifurcation with a 90° rotation). In adults, we show that while lateral bifurcation can result in well-integrated phenotypes, dorsoventral bifurcation cannot since it requires the discontinuity of at least some internal organs. The relevance of this distinction is highlighted in the case of the Ribbon Clade, a group of syllid annelids in which some species reproduce by collateral and successive gemmiparity (which involves dorsoventral bifurcation), while others grow by branching laterally. Although most known cases of bifurcation came from accidental findings in the wild or were unintentionally produced, experimental studies resulting in the induction of bifurcation of both embryos and adults are also reviewed. In embryos, these experimental studies show how mechanical or chemical disruption of the zygote can result in bifurcation. In adults, the ventral nervous system and the digestive tract seem to play a role in the induction of bifurcation. Based on the reviewed evidence, we argue that the long-forgotten study of annelid developmental anomalies should be incorporated into the growing field of annelid EvoDevo and examined with modern techniques and perspectives.

Ruptured Rudimentary Horn Pregnancy: Delayed Diagnosis.

Developmental anomalies of the genital tract result from defective fusion and absorption of various parts of Mullerian ducts in fetal life. Rudimentary horn pregnancy is a rare occurrence of one in 76,000 and one in 160,000. We present a case of a 24-year-old primigravida with ruptured rudimentary horn pregnancy initially managed in the line of an intrauterine pregnancy with severe anemia. Hemodynamic instability made us suspect ruptured rudimentary horn pregnancy and lifesaving laparotomy was performed for the same. A 1.5-liter hemoperitoneum was encountered with a right ruptured rudimentary horn. Multiple adhesions were present with necrotic tissue adherent and clumped together as tubo ovarian mass. Resection of the rudimentary horn was performed. We report this case to emphasize the need to consider rare uterine anomalies as a possibility in patients presenting with acute abdomen in early pregnancy. Obstetricians should consider these rare entities in the differential diagnosis to provide efficient management of these cases.