Maternal infectious disease may pose considerable challenges to the fetal health due to the distribution of important elements of the sanguine and lymphatic system from the mother via the umbilical cord. The mother and the fetus have a degree of interdependence that is similar to the one between the eukaryotic cell and the mitochondrion, particularly during the first half term of the pregnancy, which explains the increased appetite of the expecting mother during the first stages of the fetal development. There is a solid bridge between the adaptive immune system and the encephalon that was only discovered a few decades ago. As a result, scientists may still be in the introductory stages of research, and there might be a significant and profound degree of association between the immune system and a healthy neurological development. There is a significant link between the onset of significant maternal infectious disease and the onset of neurodevelopmental disease in the fetus, and virtually all immune cells play major roles in the promotion and inhibition of neurogenesis alike. Likewise, there is a probability that maternal infectious diseases during pregnancy represent a risk factor of fetal neurodevelopmental disease, as a pressurised development of the adaptive immune memory could result in a pressurised or inhibited neurological development, which both can result in a delayed development of certain sub-regions of the brain. For example, the fetus may display poorer social abilities and sharp analytical skills later in life, which is an important sign of neurodevelopmental disease. A pressurised development of the adaptive immune memory could not require the development of a significant form of disease, but rather just a sharp rate of immune preparation against several important pathogenic agents during the introductory stages of life, when the encephalon experiences the sharpest increase rate in development. The problem per se is not the process of immunisation, but a much sharper process of immunisation over the first stages of life in case of an exposure to one dangerous pathogen or more numerous kinds of pathogens and antigens that normally cause moderate disease morbidity. The more dangerous the microbe is, the sharper the development of the adaptive immune memory will be, and the same happens in the case of an increased number of infectious microbes and antigens that infected the cells of the mothers and the fetuses in cause, and this may, in the majority of the situations, still be the case even if the pathogens are already significantly weakened or lifeless, given that the gain of adaptive immune memory alone constitutes an important factor of neurogenesis and an increased rate of neurological development, and that the infant will become almost or fully protected against the pathogens in cause, despite not having had experienced the disease beforehand. In this case, neurodevelopmental delays are possibly not caused by an impaired neurogenesis, but by an excessive one, whilst maternal infection-associated neurodevelopmental delays may be caused by an impaired neurogenesis. Nevertheless, the aetiology of immunity-related neurodevelopmental delays may be more complex in nature and implicate a chronological and spatial sequence of induced excedentary and deficitary rates of neurogenesis, hence reflecting the incredibly complex nature and various forms of neurodevelopmental disease. It is important to mention that a single dose of infant immunisation brings significantly lower risks of adverse neurological events than the onset of a significant maternal infectious disease during pregnancy. The objective of paediatric neuro-immunological studies may be to improve the understanding of the association between a healthy immune developmental rate and a balanced ratio of the developmental rates of important brain regions and sub-regions.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p<0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

Neurodevelopmental disorders are characterised by an amalgam of genetic and epigenetic faults implicating neuronal protein-related loss-of-function and gain-of-function respectively, hence their inclusion into the category of complex diseases. Neurodevelopmental disorders are regarded as autism spectrum disorder due to this reason; that the risk factors and phenotype constitute a spectrum of faults and protein overactivity. One example of an epigenetic factor leading to the onset of neurodevelopmental delays constitutes a set of immune response-based dysregulations, as well as the excessive growth of the adaptive immune memory of the foetus or the baby following significant infectious disease during pregnancy, as well as in babies aged 0-2, given the existence of profound links between developmental immunity and developmental neurology. Given that genetic information very likely represents a form of energy, the intake of excessive pathogen-related information may transiently overload the adaptive immune memory similarly to the manner functional pathogens do whilst inducing significant illness, and if events as such occur during important stages of neuro-immunological development, then there could often be irreversible effects upon the rate of development in neurological networks that normally have a major importance in the modulation of the related cognitive and behavioural phenotype. The full extent of evidence may only be obtained via a thorough study of the applications of physical laws into biology and medicine, given the foundational role of the physical matter in the development and maintenance of life. A common misconception is that neurodevelopmental delays are characterised solely by an accumulation of protein loss-of-function incidences in the central nervous system area, rather than a disruption of neuronal region developmental rates. For example, an overexpression of neuronal proteins related to cognition factors that is accompanied by an underexpression of proteins related to social behaviour is phenotypically manifested in people with sharper rational thinking and poorer communication skills, with an impact on the abilities of decision-making as well, and this tends to be regarded as a classical example of the clinical manifestation of neurodevelopmental delays. More severe forms of autism spectrum disorder tend to implicate a more generalistic impact upon the developmental rates of key human behaviours, including those related with the development and maintenance of social and intimate relationships. Likewise, more severe implications upon regular developmental rates tend to bring a major impact upon the healthy function of related functions. As a result, lower functioning forms of neurodevelopmental delays bring fresh concerns with regards to a possible uncanny increase of incidences of deviated sexuality during years of adulthood, and in the worst cases, such deviations may lead to the planning and development of criminal activity, particularly in individuals who are or become prone to breaking the moral code that established the civilised society. What holds the concerns valid is the exponential increase in the number of lower functioning autism cases throughout the world and the major signs that such an increase will continue with a full force. One major solution to this potential future problem would be a much higher investment into awareness of the exact genetic and environmental factors that directly or indirectly result in the onset of lower-functioning autism and of the current research efforts to develop the matching support for people found in situations as such. The most important aim of future research with regards to such a scenario would be a separation of disease and disability with choices made to step into more severe forms of disease and into areas that are outside of the established moral circle.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.

Conclusions: The quantitative method provides a large-scale overview of the biometry measurements of an entire practice. Image audits can then be focused on sonographers whose measurements are outliers, avoiding the time, complexity, and expense of auditing those whose measurements fall within the expected range. We encourage commercial software developers to include tools in their ultrasound reporting software to facilitate such quantitative review.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Detailed sonographic assessment of the fetal neuroanatomy plays a crucial role in prenatal diagnosis, providing valuable insights into timely well-coordinated fetal brain development and detecting even subtle anomalies that may impact neurodevelopmental outcomes. With recent advancements in artificial intelligence (AI) in general and medical imaging in particular, there has been growing interest in leveraging AI techniques to enhance the accuracy, efficiency, and clinical utility of fetal neurosonography. The paramount objective of this scoping review is to discuss the latest developments in AI applications in this field, focusing on image analysis, automation of measurements, prediction models for neurodevelopmental outcomes, visualization techniques, and integration into clinical routine.

Preterm birth accounts for about 10% of births worldwide. Studying risk factors for perinatal brain damage is essential, as findings suggest that almost 20% of disabilities are linked to risks in the early stages of development. This research aimed to study longitudinal changes in intelligence from 6 to 8 years of age in a sample of 39 preterm children with a history of risk of brain damage and a control group of 35 children born at term. The Wechsler Intelligence Scale (WISC-IV) was used for cognitive measurement. The results showed that the preterm group obtained significantly lower scores than the control group. The working memory indicator significantly affected the interaction between age and prematurity. We consider that it is crucial to expand the knowledge we have about the neurocognitive development of premature infants both in specific cognitive domains and in age ranges so that the information obtained helps to predict the probability of presenting cognitive alterations from early stages and, therefore, to implement intervention strategies and programs based on scientific evidence and complemented in their design by clinical experience, empirical and theoretical knowledge of the different professionals involved in infant cognitive intervention.

Abstract: Background/Objectives: There are indications that the microbial composition of the maternal mucosal surfaces is associated with adverse events during pregnancy. The aim of this review is to investigate the link between vaginal microbiome alterations and gestational com-plications risk. Methods: This comprehensive literature review was performed using Medline and Scopus databases. The following search algorithm was used "Pregnancy Complications"[Mesh] AND (Vagin*) and after literature screening 44 studies were included in the final review. Results: The studies that were included investigated the association between vaginal microbial composi-tion and preterm birth, miscarriage, preeclampsia, ectopic pregnancy, gestational diabetes mellitus, chorioamnionitis and preterm premature rupture of membranes. In most of the studies, it was well established that increased microbial diversity is associated with these conditions. Also, the depletion of Lactobacillus species is linked to most of the gestational complication, while the increased relative abundance and especially L. crispatus may exerts a protective effect in favor of the pregnant woman. Several pathogenic taxa including Gardnerella, Prevotella, Sneathia, Bac-terial Vaginosis-Associated Bacteria-2, Atopobium and Megasphera seem to be correlated to higher maternal morbidity. Conclusions: Vaginal microbiome aberrations seem to have an as-sociation with pregnancy related adverse events, but more high-quality homogenous studies are necessary to reliably verify this link.

Poor perinatal mental health can have significant and lasting impacts on a woman’s overall health and the well-being of her children and family. From conception, a baby's behavior, appearance, aversions, and interests can be influenced by the prenatal environment. Thus, the quality of prenatal care is crucial. Factors such as maternal stress, environmental conditions, cravings, mood swings, hormonal changes, and emotional experiences during pregnancy can profoundly affect the baby’s behavior once born. The baby's interaction with the external world begins from conception, not just at birth. For instance, maternal depression can negatively affect both the mental and physical health of the infant. Therefore, fostering a supportive environment for expectant mothers is essential for their health and that of their unborn child. Promoting the mother’s well-being through happiness and comfort is critical.This review paper aims to synthesize current research on maternal-fetal attachment during pregnancy, its evolution, and its postpartum effects on the mother-infant relationship. It will explore how these dynamics change over time, both during pregnancy and after delivery, to provide a comprehensive understanding of the factors influencing attachment and related outcomes. As Alan Soufre, a famous developmental psychologist would state, "Attachment would begin before birth. The mother’s emotional state can shape the child’s development trajectory long before the child is born."

Huanglongbing (HLB), or citrus greening, is a devastating disease impacting citrus trees worldwide, with severe effects particularly noted in Florida. Current strategies to combat HLB have focused on aggressive replanting despite the high susceptibility of young trees to infection. In this context, it is critical to explore agronomic practices that can enhance the health and resistance of young citrus trees to HLB. Here, we demonstrate that treatment with homobrassinolide (HBr), a type of brassinosteroid, on newly planted citrus trees can delay HLB infection and improve tree health amidst the high psyllid pressure conditions endemic to Florida. Our study reveals a significant reduction in HLB infection rates in HBr-treated trees compared to control trees, with only 25% of treated trees testing positive for HLB by six months, in contrast to 100% infection in untreated trees. This delay in infection may be attributed to HBr inducing an immune response and negatively impacting psyllid performance, as subsequently demonstrated in a greenhouse experiment. Our findings suggest that HBr applications could serve as a viable strategy to enhance the resilience of citrus production against HLB, underscoring the need for further investigation into their mechanisms of action and potential role in a comprehensive pest and disease management strategy.

In vertebrates, oligodendrocytes (OLs) are glial cells of the central nervous system (CNS) responsible for the formation of the myelin sheath that surrounds the axons of neurons. The myelin sheath plays a crucial role in the transmission of neuronal information by promoting the rapid saltatory conduction of action potentials and providing neurons with structural and metabolic support. Saltatory conduction, first described in the peripheral nervous system (PNS), is now generally recognized as a universal evolutionary innovation to respond quickly to the environment: myelin helps us think and act fast. However, the function of myelin in the CNS, particularly in the brain, is not necessarily to act quickly, but rather to act correctly. In this respect, myelin should primarily play a role in synchronizing the different neuronal networks, a synchrony that occurs in the form of oscillations (or rhythms) relevant for specific information processing. Interestingly, myelin has been directly involved in different types of cognitive processes relying on brain oscillations, and myelin plasticity is currently considered to be part of the fundamental mechanisms for memory formation and maintenance. However, despite ample evidence showing the involvement of myelin in cognition and neurodevelopmental disorders characterized by cognitive impairments, the link between myelin, brain oscillations, cognition and disease is not yet fully understood. In this review, we aim to highlight what is known and what remains to be explored to understand the role of myelin in high order brain processes.

In this paper, we study a one-dimensional Bresse-Cattaneo system with infinite memories and time-dependent delay term (the coefficient of which is not necessarily positive) in the internal feedbacks. First, it is proved that the system is well-posed by means of the Hille-Yosida theorem under suitable assumptions on the relaxation functions. Then, without any restriction on the speeds of wave propagations, we establish the exponential or general decay result by introducing suitable energy and Lyapunov functionals.

The primary therapeutic method for correcting hyperglycemia today is diet therapy. Lipids are not only a source of nutrients but can also act as initiators of adipocyte differentiation in the fetus, which explains the development of fetal macrosomia and future metabolic disorders in children born to mothers with gestational diabetes mellitus (GDM). Changes in the profile of circulating lipids in the maternal bloodstream, depending on adherence to a rational diet among mothers with GDM and the development of fetal macrosomia, is a complex and not fully understood process. The aim of the study was to examine the characteristics of the lipid profile in the blood plasma of pregnant women with GDM in all trimesters of pregnancy based on adherence to diet therapy. The design of the clinical part of the work was carried out within the framework of a 'case-control' study.The study included 110 women, 80 of whom were in the control group, 20 in the group with GDM adhering to the diet, and 10 in the group with GDM not adhering to the diet. The laboratory part was conducted as part of a longitudinal dynamic study with venous blood samples taken at three points: 11-13, 24-26, and 30-32 weeks of pregnancy.A significant impact of diet therapy on the blood lipid composition throughout pregnancy was demonstrated, starting as early as the first trimester. ROC analysis showed high effectiveness of the developed models with an AUC of 0.98 for the "30-32 weeks" model, with sensitivity and specificity of 1 and 0.9, respectively. An association was found between diet, maternal blood lipid composition at 32 weeks of pregnancy, and newborn weight. The direction of changes in the lipid spectrum during the development of macrosomia and diet therapy is diametrically opposed. This confirms at the molecular level that diet therapy can normalize not only carbohydrate but also lipid metabolism in the mother and fetus. Based on the obtained data, it can be suggested that after validation, the developed models could be used to refine the prognosis of macrosomia development based on the lipid profile of blood plasma at different stages of pregnancy.

This work investigates the stability conditions for linear systems with time-varying delays via augmented Lyapunov-Krasovskii functional(LKF). Two types of augmented LKFs with cross terms in integral are suggested to improve the stability conditions for interval time-varying linear systems. Through this work, the compositions of the LKFs are considered to enhance the feasible region of stability criterion for linear systems. Mathematical tools such as Wirtinger-based integral inequality(WBII), zero equalities, reciprocally convex approach, and Finsler’s lemma are utilized to solve the problem of stability criteria. Two sufficient conditions are derived to guarantee the asymptotic stability of the systems using linear matrix inequality(LMI). First, asymptotic stability criteria are induced by constructing the new augmented LKFs in Theorem 1. And then simplified LKFs in Corollary 1 are proposed to show the effectiveness of Theorem 1. Second, asymmetric LKFs are shown to reduce the conservatism and the number of decision variables in Theorem 2. Finally, the advantages of the proposed criteria are verified by comparing maximum delay bounds in two examples. Two numerical examples show that the proposed Theorem 1 and 2 obtained less conservative results than existing outcomes. Also, Example 2 shows that the asymmetric LKF methods of Theorem 2 can provide larger delay bounds and fewer decision variables than Theorem 1’s in some specific systems.

The goal of the study is to assess the potential correlation between maternal Sars-cov-2 infection , detected three months before the second trimester anomaly scan, and fetal iperecogenicity in order to determine whether or not this could be considered a predictive factor for maternal-fetal complications . The study included 48 pregnant women who did not have any clear maternal or fetal problems. These individuals had an anomaly scan in the second trimester, as well as amniocentesis and fetal cariotyping, and then RT-PCR testing on their placental tissue after birth to rule out transplacental transmission. There have been no reports of fetal abnormalities via amniocentesis or fetal cariotyping. The patients experienced a high rate of spontaneous births (83%). Fetal development problems (2%) and premature delivery (4%) were uncommon, although placental swabs revealed a possibility of viral transmission across the placenta itself. To the best of our knowledge, this is the first observational study to show that detecting isolated intestinal hyperechogenicity during an abnormality scan in fetuses of women infected with Sars-Cov-2 in the previous three months does not appear to be a predictor of poor maternal-fetal outcomes, but may be linked to transplacental virus transmission.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

Age is the primary risk factor for neurodegenerative diseases such as Alzheimer’s and Huntington’s disease. Alzheimer’s disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer’s, Huntington’s, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling proteotoxicity in Alzheimer’s and Huntington’s disease-related, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO) delays age-associated paralysis in both models. This effect on paralysis was independent of protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event liking HAAO knockdown to delayed paralysis. This work demonstrates potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.

The fetal splenic artery pulsatility index (PI) is a parameter that reflects fetal well-being and has been used as a predictor of adverse pregnancy outcomes. The aim of this study was to investigate the predictive value of splenic artery PI in GDM class A1 cases for NICU admission. In this prospective case controlled study, only sixty single pregnancy cases diagnosed with gestational diabetes mellitus class A1 were evaluated. Fetal splenic artery Doppler parameters Peak systolic velocity (PSV), Pulsatility index (PI), Resistivity index (RI) and End diastolic velocity (EDV) were measured in all cases. The rate of re-quirement of need of neanoatal intensive care unit was noted. In cases with need fetal intensive care, fetal splenic PI index was found to be statistically significantly lower than in healthy cases without it (0.94 ± 0.29 vs. 1.70 ± 0.53, respectively, p

Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and known to be a leading cause of inherited intellectual disability globally. It results in a range of intellectual, developmental, and behavioral problems. Fragile X premutation associated conditions (FXPAC), also caused by a smaller CGG expansion (55 to 200 CGG repeats) in the FMR1 gene, is linked to other conditions that increase morbidity and mortality for affected persons. Limited research has been conducted on the burden, characteristics, diagnosis, and management of these conditions in Africa. This comprehensive review provides an overview of the current literature on FXS and FXPAC in Africa, epidemiology, clinical features and challenges faced, such as discrimination against affected persons, limited awareness and research, poor access to resources and genetic services and treatment. It further provides an in-depth analysis of the existing worldwide data for the diagnosis and treatment of these disorders. This review will improve understanding of FXS and FXPAC in Africa by incorporating existing knowledge, identifying research gaps, and potential topics for future research to enhance the well-being of individuals and families affected by FXS and FXPAC in the region.

The theory of one-photon ionization and two-photon above-threshold ionization is formulated for applications to heavy atoms in attosecond science using the Dirac-Fock formalism. A direct comparison of the Wigner-Smith-Eisenbud delays for photoionization is made with delays from the Reconstruction of Attosecond Beating By Interference of Two-photon Transitions (RABBIT) method. Photoionization by an attosecond pulse train, consisting of monochromatic fields in the extreme ultraviolet range, is computed with many-body effects at the level of the Relativistic Random Phase Approximation (RRPA). Subsequent absorption and emission processes of infrared laser photons in RABBIT are evaluated using static ionic potentials as well as asymptotic properties of relativistic Coulomb functions. As expected, light elements, such as Argon, show negligible relativistic effects, while heavier elements, such a Krypton and Xenon, exhibit delays that depend on the fine-structure of the ionic target. The relativistic effects are notable close to ionization thresholds and Cooper minima with differences in fine-structure delays predicted to be as large as tens of attoseconds. The separability of relativistic RABBIT delays into a Wigner-Smith-Eisenbud delay and a universal continuum--continuum delay is studied with reasonable separability found for photoelectrons emitted along the laser polarization axis in agreement with prior non-relativistic results.

Children from rural areas face numerous possibilities for neurodevelopmental conditions that may compromise their well-being and optimal development. Neuropsychology and electroencephalography (EEG) have shown strong agreement in detecting correlations between these two variables and suggest an association with specific environmental and social risk factors. The present meta-analysis aims to integrate the qualitative and quantitative EEG findings, their relationship with cognitive impairment in children living in vulnerable or rural environments, and the main risk factors influencing EEG abnormalities. The method for this purpose was based on a systematic string-based review from Ebscohost and Web of Science, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Qualitative and quantitative analyses were conducted from the outcomes that complied with the selected criteria. A total of 92 records were identified; however, only 20 were eligible, considering 11 for qualitative and 9 for quantitative analysis. The findings highlight a significant amount of literature on EEG and its relation with cognitive impairment from studies in children with epilepsy and malnutrition. In general, there is evidence about the advantages of implementing EEG diagnosis and research techniques in children living under risk conditions. Further research is needed to better describe and integrate the state of the art regarding EEG features extraction.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

The dynamical processes of living systems are characterized by the cooperative interaction of many units. This claim enables us to portray the embryo-fetal development of the central and peripheral nervous systems in terms of assemblies of building blocks. We describe how the structure and arrangement of nervous fibers is - at least partially - dictated by biophysical and topological constraints. The far-flung field of soft-matter polymers/nematic colloids sheds new light on the neurulation in mammalian embryos, suggesting an intriguing testable hypothesis: the development of the central and peripheral nervous systems might be correlated with the occurrence of local thermal changes in embryo-fetal tissues. Further, we show a correlation between the fullerene-like arrangement of the cortical microcolumns and the Frank-Kasper phases of artificial quasicrystals assemblies. The last, but not the least, we explain how and why the multisynaptic ascending nervous fibers connecting the peripheral receptors to the neocortical areas can be viewed as the real counterpart of mathematical tools such as knot theory and braid groups. Their group structure and generator operations point towards a novel approach to long-standing questions concerning human sensation and perception, leading to the suggestion that the very arrangement and intermingling of the peripheral nervous fibers contributes to the cortical brain activity. In touch with the old claims of D’Arcy Thompson, we conclude that the arrangement and the pattern make the function in a variety of biological instances, leading to countless testable hypotheses.

Fetal Alcohol Spectrum Disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments, which can have profound and lasting effects on individuals throughout their lives impacting their health, social interactions, psychological well-being and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress on epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

When researching rock blasting, the design parameters used for the analysis are usually the ge-ometric and charging ones. This study is based on a different approach, and focuses on the effect of timing, in specific the role of delays in the initiation sequence. The data come from the results of full-scale blasts. The experimental setting and location allowed to consider all parameter other than the number of delays as a constant. The experimental results are analyzed relating the delay var-iables to fragmentation and KPIs of downstream operations. It is shown how increasing the number of delays per unit of blasted rock and reducing simultaneous adjacent holes produces finer fragmentation, reduces the amount of fines, facilitates the secondary operations and reduces the risk of flyrock.

There is disagreement on the associations between chorioamnionitis and pneumonia/sepsis, respiratory distress syndrome (RDS), and bronchopulmonary (BPD)dysplasia, three pulmonary outcomes of concern for preterm newborns. Determining clear correlations is challenging due to the intricacy of the prenatal, postnatal, and therapeutic practices that affect the diagnosis of RDS, pneumonia/sepsis, and BPD, two long-term outcomes, as well as their short- and long-term consequences. Owing to the interconnected nature of the variables, the vaguely defined fetal exposures, and the imprecise identification of disorders like RDS and BPD, multivariant studies of huge data sets are unreliable methods for defining associations. On the other hand, research using animal models offers reliable data regarding the effects of exploratory chorioamnionitis on the fetal lung. Understanding the clinical intricacy and the experimental consequences of chorioamnionitis together will help us understand on the impact on the fetal lung .

Human induced pluripotent stem cells (hiPSCs) have two characteristic abilities 1) self-renewal and 2) differentiation into all cell types in the human body. It is this ability of iPSCs to differentiate into any desired cell type that makes them amenable to disease modeling. iPSCs can further be engineered to carry a disease-specific mutation or be derived from patients to phenocopy the disease. To model neurodegenerative/neurodevelopmental disorders iPSCs are differentiated into neurons. This chapter describes protocols for two different approaches to generate neurons from iPSCs, first using dual SMAD inhibition to generate neural progenitor cells which are then differentiated into neurons, and second using single transcription factor (NGN2) over-expression to drive differentiation of iPSCs directly into neurons.

The 20–60-μm axon initial segment (AIS) is proximally located at the interface between the axon and cell body. AIS has characteristic molecular and structural properties regulated by the crucial protein, ankyrin-G. The AIS contains a high density of Na+ channels relative to the cell body, which allows low thresholds for initiation of action potential (AP). Molecular and physiological studies have shown that the AIS is also a key domain for the control of neuronal excitability by homeostatic mechanisms. The AIS has high plasticity in normal developmental processes and pathological activities such as injury, neurodegeneration, and neurodevelopmental disorders (NDDs). In the first half of this review, we provide an overview of the molecular, structural, and ion-channel characteristics of AIS, AIS regulation through axo-axonic synapses, and axo-glial interactions. In the second half, to understand the relationship between NDDs and AIS, we discuss the activity-dependent plasticity of AIS, the human mutation of AIS regulatory genes, and the pathophysiological role of the abnormal AIS in the NDD model animals and patients. We propose that AIS may provide a potentially valuable structural biomarker in response to abnormal network activity in vivo as well as a new treatment concept at the neural circuit level.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are prevalent neurodevelopmental disorders with distinct diagnostic criteria but significant overlap in symptoms and comorbidity. This article explores the relationship between ADHD and ASD, examining their common neurodevelopmental origins, shared features, and distinct trajectories. Both disorders are highly heritable, with genetic studies identifying shared genetic variants and neurobiological abnormalities. Environmental factors, including prenatal and perinatal exposures, also contribute to their etiology. Despite these commonalities, ADHD and ASD exhibit distinct developmental trajectories, cognitive profiles, and long-term outcomes. Understanding the interplay between these disorders is crucial for developing effective diagnostic and treatment strategies. Future research should focus on elucidating the underlying mechanisms and developing targeted interventions for individuals with comorbid ADHD and ASD.

Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence development of both ASD and PD with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

This paper is concerned with the optimal linear quadratic Gaussian (LQG) control problem for discrete time-varying system with multiple input delays and multiplicative noises. The main contributions are two-fold. Firstly, when the state variables can be observed exactly, we obtain a necessary and suffcient condition for the multiple-delays system in terms of the non-homogeneous relationship between the state and costate, which is the solution to the coupled forward and backward stochastic difference equations. Secondly, when the state variables are partially observed, we derive a suboptimal linear output feedback controller for the discrete-time system based on the obtained results of the optimal LQG control. Numerical examples are shown to illustrate the proposed algorithm.

Vitamin D deficiencies are very common in pregnant women, raising concerns about adverse health outcomes in children. This issue has hardly been studied in multiple pregnancies, the prevalence of which has been steadily increasing. Therefore, our study investigated the relationship between newborns’ anthropometric parameters and the concentration of 25(OH)D in maternal blood of women with twin pregnancies and umbilical cord blood. The study included 50 women who gave birth after the 36th week of twin gestation. 25(OH)D was determined in maternal blood collected during the antenatal period and in the umbilical cord blood of 100 newborns. Anthropometric parameters of the newborns (birth weight, length, head and chest circumference) were obtained from hospital records. Data on nutrition and lifestyle during pregnancy were collected from the patients during an interview conducted by a dietitian. No relationship between maternal and neonatal cord blood vitamin D concentrations and any of the anthropometric parameters of the newborns was found. However, only 6% of the mothers and 13% of the newborns had vitamin D deficiency (≤20 ng/mL). The type of pregnancy and maternal height were the main factors associated with neonatal size. Newborns from dichorionic pregnancies were on average 202 g heavier (p<0.001) and 1 cm longer (p=0.006) than newborns from monochorionic pregnancies. Newborns of mothers ≤ 160 cm in height had on average 206 g lower birth weight (p=0.006) and were 3.5 cm shorter (p=0.003) compared to newborns of taller mothers. Therefore, in our study, neonatal size of the twins was not related to the vitamin D status but to other factors such as the type of pregnancy and maternal height.

Electronic cigarette (ecig) use in pregnancy is common, but potential effects on fetal development are largely unknown. The study goal was to examine the association between ecig exposure and fetal growth. Data were extracted from medical charts in this single site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used ecigs throughout pregnancy and non-ecig user controls. Fetal size measurements from second and third trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for ecig exposed compared to controls. By the third trimester, femur length difference was 28.5 points, with fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal ecig exposure, becoming larger and impacting more parameters with increasing gestation. While additional study is warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following ecig exposure in pregnancy, and suggests that ecigs may not be a “safer” alternative to combustible cigarette smoking in pregnancy.

Fetal weight estimation before delivery is important in obstetrics, which assists doctors diagnose abnormal or diseased cases. Linear regression based on ultrasound measures such as bi-parietal diameter (bpd), head circumference (hc), abdominal circumference (ac), and fetal length (fl) is common statistical method for weight estimation but the regression model requires that time points of collecting such measures must not be too far from last ultrasound scans. Therefore this research proposes a method of early weight estimation based on expectation maximization (EM) algorithm so that ultrasound measures can be taken at any time points in gestational period. In other words, gestational sample can lack some or many fetus weights, which gives facilities to practitioners because practitioners need not concern fetus weights when taking ultrasound examinations. The proposed method is called dual regression expectation maximization (DREM) algorithm. Experimental results indicate that accuracy of DREM decreases insignificantly when completion of ultrasound sample decreases significantly. So it is proved that DREM withstands missing values in incomplete sample or sparse sample.

Background Corpus callosum abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosum abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications on the postnatal outcome. Methods In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. Results The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%) and hypoplasia with dysplasia (4.2%). Amongst them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. Conclusion The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a diagnosis suspected on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in the cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity and a high-fat diet in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

Prenatal maternal feeding plays an important role in fetal development and has potential to cause long-lasting epigenetic modifications. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs that serve as one epigenetic mechanism. Though miRNAs have crucial roles in fetal programming, growth, and development, there are limited data regarding maternal diet and sheep miRNA expression. Therefore, weanalyzed high and low maternal dietary protein for miRNA expression in sheep fetal longissimus dorsi. Pregnant ewes were fed an isoenergetic high-protein (HP, 160–270 g/day), low-protein (LP, 73–112 g/day), or standard protein diet (SP, 119–198 g/day) during pregnancy. miRNA expression profiles were evaluated using the Affymetrix GeneChip miRNA 4.0 Array. Twelve up-regulated, differentially expressed miRNAs (DE miRNAs) were identified targeting 65 genes. The oar-3957-5p miRNA was highly up-regulated in LP and SP compared to HP. Previous transcriptome analysis identified integrin and non-receptor protein tyrosine phosphatase genes targeted by miRNAs detected in the current experiment. A total of 28 GO terms and 10 pathway-based gene sets were significantly (padj &lt; 0.05) enriched in target genes. Most genes targeted by identified miRNAs are involved in immune and muscle disease pathways. Our study shows dietary protein intake during pregnancy affects fetal skeletal muscle epigenetics via miRNA expression.

Sensory processing challenges are crucial yet often neglected aspects in the care of children with neurodevelopmental disorders and genetic conditions. They represent a key area of interest in neuroscience, as they significantly impact children's daily functioning and quality of life. This observational study examines the characteristics of these challenges in a group of 614 children, aged 3 to 14 years and 11 months, divided into three groups: 183 with neurodevelopmental disorders (Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, developmental delays, learning disorders), 89 with genetic conditions (22q11.2 Deletion Syndrome, Williams Syndrome, Pseudohypoparathyroidism), and 342 controls. Sensory processing was assessed using the Sensory Profile 2 (SP2). Results indicated that children with neurodevelopmental disorders and genetic conditions exhibited significant sensory processing difficulties compared to controls. The SP2 identified sensory challenges across different sensory systems, with varying configurations depending on the diagnosis. Children with neurodevelopmental disorders and genetic conditions show marked sensory processing challenges impacting daily lives and well-being. These findings highlight the importance of early identification and tailored evidence-based interventions to address these specific sensory processing issues. Further research should explore the long-term impact of these interventions in these different populations and their integration into broader therapeutic programs.

Attention-Deficit/Hyperactivity Disorder (ADHD) is traditionally conceptualized within a framework emphasizing deficits in attention regulation and executive function. However, emerging evidence from the fields of predictive coding and active inference offers a novel lens through which to understand ADHD not merely as a disorder of attention but as a distinctive mode of neurodevelopmental variation. This article synthesizes current research and theoretical models to propose a redefined understanding of ADHD. By integrating insights from Ryan Smith, Paul B. Badcock, and Karl J. Friston (2020), we explore the premise that individuals with ADHD exhibit unique differences in how their brains generate and update predictions about the environment, leading to the characteristic behavioral patterns observed in ADHD. We argue that ADHD involves a divergence in the brain's predictive models and its ability to minimize prediction error, impacting sensory processing, attention allocation, and motor control. This perspective illuminates the adaptive aspects of ADHD, suggesting that what are often labeled as deficits could also reflect an adaptive fit to certain environmental contexts, underscoring the role of neurodiversity in human evolution. Furthermore, we discuss the implications of this reconceptualization for clinical practice, including diagnosis, treatment, and support for individuals with ADHD, emphasizing approaches that align with their unique neurocognitive profiles. This article calls for a shift in the narrative surrounding ADHD, advocating for a model that appreciates the complexity and adaptiveness of neurodevelopmental diversity.

The Golgi apparatus (GA) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GA are implicated in a wide range of neurodegenerative diseases. GA defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GA regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GA during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GA? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GA will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GA in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HAADF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GA.

Evidence that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible children has mounted for more than a decade. Evidence is diverse, including extensive work with laboratory animals, otherwise unexplained associations, factors associated with the metabolism of acetaminophen, and some limited studies in humans. Although evidence has reached an overwhelming level and has been reviewed in detail recently, some controversy remains. In this narrative review, some of those controversies are evaluated. First, the associations through time between acetaminophen use and the prevalence of neurodevelopmental disorders are considered. A systematic review reveals that the use of acetaminophen in the pediatric population was never tracked carefully, but historical events that affected use of the drug were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Second, problems with exclusive reliance on results from meta-analyses of large datasets and from studies involving small time frames of drug exposure are reviewed. Third, the potential bias in a study designed to separate the role of vaccines and acetaminophen in the induction of autism spectrum disorder (Autism 2008;12:293-307) is carefully evaluated. Finally, evidence demonstrating why some children are susceptible to acetaminophen-induced neurodevelopmental injury is examined. It is concluded that, at least among the factors considered, there is no valid rationale for controversy regarding the conclusion that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible babies and small children.

The purpose of this paper is to find the time optimal control to a target set for semilinear stochastic functional differential equations involving time delays or memories under general conditions on a target set and nonlinear terms even though the equations contain unbounded principal operators. Our research approach is construct a fundamental solution for corresponding linear systems and establish variations of constant formula of solutions for given stochastic equations. The existence result of time optimal controls for one point target set governed by the given semilinear stochastic equation is also established.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading to adverse fetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on fetal HPA axis function and postnatal offspring development, hence this study. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone were measured in all dams and pups. Glucose tolerance and expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase in pups ACTH and corticosterone concentrations, impaired glucose tolerance and dysregulated MR and GR expression in the PD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by trans-generationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for pregnancy-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish the exposure threshold to the fetus due to nutrient deficiencies or other environmental factors that can lead to clinically relevant epigenetic changes that modulate disease risks. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development.

The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and then identify decelerations and accelerations. These steps can potentially be automated and made more objective by signal processing analysis. Various methods have been described in the literature but there are no open-source programs for performing these steps. The MATLAB toolbox presented here comprises a standard signal pre-processing function, 11 re-coded literature methods for fetal heart rate analysis, a signal viewer (enabling annotation by an expert) and an evaluation procedure with various criteria measuring intrarater agreement.

Recurrent neural networks (RNNs) transmit information over time through recurrent connections. In contrast, biological neural networks use many other temporal processing mechanisms. One of these mechanisms is the inter-neuron delays caused by varying axon properties. Recently, this feature was implemented in echo state networks (ESNs), a type of RNN, by assigning spatial locations to neurons and introducing distance-dependent inter-neuron delays. These delays were shown to significantly improve ESN task performance. However, thus far it is still unclear why distance-based delay networks (DDNs) perform bettern than ESNs. In this paper, we show that by optimizing inter-node delays, the memory capacity of the network matches the memory requirements of the task. As such, networks concentrate their memory capabilities to the points in the past which contain the most information for the task at hand. Moreover, we show that DDNs have more total linear memory capacity, with the same amount of non-linear processing power.

Introduction: Laeverin is an extravillous trophoblast marker playing a significant role in the trophoblast migration. The purpose of this study was to evaluate the association between the amniotic and serum laeverin concentrations at 16-22 weeks of gestation and the fetal and placental ultrasound measurements in healthy, unaffected pregnancies. Materials and methods: This was a prospective cross-sectional study. Pregnant women with singleton pregnancies undergoing amniocentesis were recruited consecutively. Fetal structural malformations and/or aneuploidy were exclusion criteria. Fetal biometric parameters and placental growth/perfusion were measured in 44 high-risk pregnancies who had no pregnancy complication and any other chronic disease. Maternal serum and amniotic levels of laeverin were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing slightly with the maternal age in mid-gestation. Serum laeverin level correlated negatively slightly with head size of the fetus with the gestational length at delivery (β=-0.38, 95% confidence interval (CI) -0.03-0.01), while the amniotic laeverin level correlated strongly with the abdominal circumference of the fetus (β=-0.64, 95% CI: -0.03-0.01). Furthermore, laeverin level in the amnion correlated moderately and positively with the placental volume (β=0.46, 95% CI: 0.01-0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denotes the fetoplacental growth in uncomplicated high-risk pregnancies.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

BackgroundIntracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasound (US) and MRI. Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of two cases of prenatal ICH.Cases presentationThe first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530g.ConclusionFetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH.

Histamine (HA), a biogenic monoamine, exerts its pleiotropic effects through four H1R–H4R histamine receptors, which are also expressed in brain tissue. Together with the projections of HA-producing neurons located within the tuberomammillary nucleus (TMN), which innervate most areas of the brain, they constitute the histaminergic system. Thus, while remaining a mediator of the inflammatory reaction and immune system function, HA also acts as a neurotransmitter and a modulator of other neurotransmitter systems in the central nervous system (CNS). Although the detailed causes are still not fully understood, neuroinflammation seems to play a crucial role in the etiopathogenesis of both neurodevelopmental and neurodegenerative (neuropsychiatric) diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease (AD) and Parkinson's disease (PD). Given the increasing prevalence/diagnosis of these disorders and their socioeconomic impact, the need to develop effective forms of therapy has focused researchers' attention on the brain's histaminergic activity and other related signaling pathways. This review presents the current state of knowledge concerning the involvement of HA and the histaminergic system within the CNS in the development of neurodevelopmental and neurodegenerative disorders.

Organophosphate pesticides (OPs) are toxic substances that contaminate aquatic environments, interfere with the development of the nervous system, and induce Neurodevelopmental Toxicity (NDT) in animals and humans. The canonical mechanism of OP neurotoxicity involves the inhibi-tion of acetylcholinesterase (AChE), but other mechanisms non-AChE are also involved and not fully understood. We used network toxicology and molecular docking to identify molecular targets and toxicity mechanisms common to OPs. Targets related to diazinon-oxon, chlorpyrifos oxon, and paraoxon OPs were predicted using the Swiss Target Prediction and PharmMapper databases. Targets related to NDT were compiled from GeneCards and OMIM databases. In order to construct the protein-protein interaction (PPI) network, the common targets between OPs and NDT were imported into the STRING. Networks topological analyses identified EGFR, MET, HSP90AA1, and SRC as hub nodes common to the three OPs. Using Reactome pathway and gene ontology we found that signal transduction, axon guidance, cellular responses to stress, and glutamatergic signaling activation play key roles in OP-induced NDT.

Adult mesenchymal stem cells (MSCs) are a promising cell source for tissue regeneration. However, ex vivo expansion results in cell senescence; cells lose their proliferation and differentiation capacity. Fetal MSCs can be an alternative due to their robust proliferation and differentiation capacities as well as immune privilege properties. Given the rejuvenation effect of decellularized extracellular matrix (dECM) on adult MSCs, it remains unknown whether dECM influences the regenerative potential of fetal stem cells. In this study, passage five fetal nucleus pulposus cells (fNPCs) and fetal synovium-derived stem cells (fSDSCs) were expanded on dECMs deposited by fNPCs (NECM) and fSDSCs (SECM) for one passage with expansion on tissue culture plastic (Plastic) as a control. We found that dECM expanded fNPCs and fSDSCs exhibited both similarities and differences in expression of stemness genes and surface markers. Expanded fNPCs yielded more differentiated pellets after chondrogenic induction but no adipogenic differentiation following adipogenic induction in both Plastic and dECM groups than the corresponding fSDSC group. Despite a significant increase in fNPCs, dECM expanded fSDSCs exhibited no increase in chondrogenic potential; however, compared to the Plastic group, dECM expanded fSDSCs exhibited a small increase in osteogenic potential and a great increase in adipogenic potential. These results suggest that fNPCs are more sensitive to NECM rejuvenation for cartilage tissue engineering and regeneration; in contrast, dECMs exhibited limited effects on fSDSC rejuvenation in chondrogenic capacity except for enhanced adipogenic capacity following expansion on SECM.

Background: Fetal overgrowth is related to many perinatal complications including stillbirth, cesarean section, maternal and neonatal injuries, and shoulder dystocia. It is related to maternal diabetes, obesity, and gestational weight gain, but also happens in low-risk pregnancies. There is ongoing discussion regarding definitions, methods of detection, and classification. The method used for detection is of crucial importance as it draws a line between those at risk and low-risk populations. Methods: In this a narrative review of relevant evidence identified through PubMed search with one of the general terms (macrosomia, large-for-gestational-age) combined with the outcome of interest. Results: This revive summarizes evidence on the relation of fetal overgrowth with stillbirth, cesarean sections, shoulder dystocia, anal sphincter injury, and hemorrhage. Customized growth charts help to detect mothers and fetuses at risk of those complications. Relations between fetal overgrowth and diabetes, maternal weight, and gestational weight gain. Conclusions: a substantial proportion of complications are an effect of the fetus growing above its potential and should be recognized as a new dangerous condition of Fetal Growth Acceleration

Children and young people (CYP) with neurodevelopmental disorders (NDDs) may be particularly vulnerable to adverse mental health effects due to the COVID-19 pandemic. We conducted a cross-sectional U.K parent-reported study from 2nd April-2nd June 2020, using the Strengths & Difficulties Questionnaire. CYP with NDDs (n=371) compared to neurotypical controls, had a higher prevalence of emotional symptoms (42% vs 15%), conduct problems (28% vs 9%), and lower prosocial behaviours (54% vs 22%). Those with attention-deficit/hyperactivity disorder showed inflated conduct, and those with autism spectrum disorder exhibited decreased prosocial behaviours. Females with ASD had higher emotional symptoms compared to males.

Intellectual disability with speech delay and behavioural abnormalities as well as hypotonia, seizures, feeding difficulties and cra-niofacial dysmorphism are the main symptoms associated with pathogenic variants of ZMYND11 gene. The range of clinical mani-festations of ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present 2 previ-ously unreported paediatric patients with neurodevelopmental features diagnosed with missense variants in ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinemic hypoglycaemia (HH), a symptom that was not de-scribed before in published works. Although the reason for the occurrence of HH in our proband is not clear, it is likely that it broadens the spectrum of symptoms characteristic of ZMYND11 syndrome. Thus, this paper contributes to extending the range of possible manifestations of ZMYND disease and further supports its association with neurodevelopmental challenges.

This study aimed to evaluate the positive effect of autumn olive berries (AOB) extract on aging delay by improving the lipid metabolism of middle-aged C. elegans who became obese due to high glucose (GLU) diet. As a result of investigating the total phenol content and DPPH radical scavenging ability of freeze- or spray-dried AOB, freeze-dried AOB showed better antioxidant potential. Afterward, through HPLC analysis, it was confirmed that catechin was the main compound in the polyphenols of AOB. Therefore, we used freeze-dried AOB in subsequent in vivo experiments. AOB inhibited lipid accumulation in both the young adult and middle-aged groups in a concentration-dependent manner under both normal and 2% GLU conditions. Additionally, AOB inhibited ROS accumulation in a concentration-dependent manner under normal and 2% GLU conditions in the middle-aged worms. In particular, AOB also increased the number of body bending and egg production in middle-aged worms. To confirm the intervention of genetic factors related to lipid metabolism in the effect of AOB, body lipid accumulation was confirmed using worms deficient in the daf-16, atgl-1, aak-1, and akt-1. Regarding the effect of AOB on reducing lipid accumulation, the impact was nullified in daf-16 deficient worms under the 2% GLU condition and nullified in both daf-16 and deficient worms under fasting conditions. This means that AOB regulates lipogenesis and lipolysis by mediating daf-16 and atgl-1 in middle-aged worms. Our results suggest that AOB contributes to the aging delay effect by improving lipid metabolism in metabolic impaired middle-aged worms.

Abstract: (1) Background: to find out how COVID-19 infection during pregnancy affects the outcome of the pregnancy; (2) Methods: 166 SARS-CoV-2-positive pregnant women formed the study group. 128 SARS-CoV-2-negative pregnant women formed the control group. Anatomopathological study of the placenta was performed in all cases; (3) Results: Placental insufficiency appeared in 38 patients (22.9%) of the study group and in 17 patients (13.2%) in the control group (p=0.016). Villitis appeared in 50 patients (30.1%) of the study group and in 16 (12.6%) in the control group (p=0.000). 166 COVID-19 positive patients were further subdivided, into those with anatomopathological affection of the placenta, and those without. When gestational age between patients with placental insufficiency and those without it are compared, a difference of 4.38 days is obtained (p=0.0393). If we compare neonatal weight between patients with placental insufficiency and those without it, a difference of 406.4 grams is obtained (p=0.0000). When gestational age between patients with villitis and those with-out it are compared, a difference of 3.2 days is found (p=0.0919). When neonatal weight between patients with villitis and those without it are compared, a difference of 242.2 grams is obtained (p=0.0018). (4) Conclusions: COVID-19 infection during pregnancy may produce lower fetal weight and shorter gestational length.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. In addition, tadalafil protected cerebral nerve development in FGR offspring. The clinical trials we have conducted to date, including a case–control study, a phase I trial, and a phase II trial, have indicated the efficacy of tadalafil in prolonging pregnancy, as well as a good safety profile for fetuses and neonates. The number of fetal, neonatal, and infant deaths was significantly lower in those receiving tadalafil treatment group than that in controls, and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Pregnancy entails bidirectional interactions between the developing fetus, the maternal tissues, and the organ systems. To this end, the phenomenon of migration of fetal cells (FCs) into the maternal circulation is poorly understood. Here, we review literature underlying the migration of FCs from the placenta to the maternal circulation, which is likely a dynamic process, including trophoblast invasion, placental angiogenesis, modulation of maternal immune responses, and enlargement of maternal organs. As placental neovascularization fosters direct connections between fetal and maternal circulatory systems, the trophoblast, a pivotal to placental development, adeptly deploys an array of invasive strategies to breach maternal tissue barriers, facilitating FC escapade into the maternal circulation. The intricate balance struck by the maternal immune system, which both acts as a guardian against potential foreign cell threats and orchestrates a niche conducive to FC survival and differentiation, is facilitated by finely tuned interactions among regulatory T cells, cytokines, and inhibitory receptors. FC presence in mothers’ circulation may be clinically relevant and unveil novel molecular participants like lncRNA, exosomes, and intricate signaling pathways that drive innovative clinical approaches for diagnostics and therapeutics. Ongoing research should reshape our knowledge of pregnancy and maternal-fetal health by improving our understanding of fetal-maternal interactions.

Efficient commencement of clinical trials is pivotal for their successful execution. The purpose of this study was to determine and examine the factors that contribute to trial start-up delays. The study assessed 20 clinical trials' start-up stages in order to identify relevant variables. Results showed that trials with an emphasis on devices, trials that did not outsource, trials that utilized less auxiliary services, and trials that employed interventional designs had quicker start-up times than observational studies. Furthermore, approval times were substantially shortened by using a centralized Institutional Review Board (IRB) rather than a local IRB. Furthermore, compared to studies that successfully enrolled subjects, those who failed to do so required more time to complete contracts and budgets and secure IRB clearance. This study underscores the diverse impact of clinical trial features on start-up timelines. Understanding these factors is crucial for optimizing the initiation process of clinical trials.

This paper studies the finite-time synchronization problem of fractional-order stochastic memristive bidirectional associative memory neural networks (MBAMNNs) with discontinuous jumps. A novel criterion for finite-time synchronization is obtained by utilizing the properties of quadratic fractional-order Gronwall inequality with time delay and the comparison principle. This criterion provides a new approach to analyze the finite-time synchronization problem of neural networks with stochasticity. Finally, numerical simulations are provided to demonstrate the effectiveness and superiority of the obtained results.

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally-induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.

Early childhood is important for future cognitive and educational outcomes. Programs overcoming barriers to engagement in early education for Indigenous children must address family cultural needs and target developmental delays. This systematic review identifies culturally adapted programs to improve cognitive, emotional and developmental delays among young children, in response to an identified priority of a remote Indigenous community. Five databases (the Cochrane Library, Embase, Medline, Scopus and CINAHL) were searched for English language papers in January 2018. Study quality was assessed and findings analysed thematically. Findings were presented to the community at an event with key stakeholders, to determine their inclusion and face validity. Seven relevant studies, published between 1997-2013, were identified by the researchers and each study was supported by the community for inclusion. Two studies focused on Native American children and five studies included children from non-Indigenous disadvantaged backgrounds. Findings were reported narratively across four themes: Storytelling to improve educational outcomes; Family involvement improved development; Culturally adapted Cognitive Behavioral Therapy to reduce trauma; Rewards-based teaching to improve child attention. Limited published research on culturally adapted and safe interventions for children with cognitive, emotional and developmental delay exists but these four themes from seven studies identify useful components.

In this paper, Lyapunov-Razumikhin technique, design of state-dependent switching laws, a fixed point theorem and variational methods are employed to derive the existence and the unique existence results of (globally) exponentially stable positive stationary solution of delayed reaction-diffusion cell neural networks under Dirichlet zero boundary value, including the global stability criteria \textbf{in the classical meaning}. Next, sufficient conditions are proposed to guarantee the global stability invariance of ordinary differential systems under the influence of diffusions. New theorems show that the diffusion is a double-edged sword in judging the stability of diffusion systems. Besides, an example is constructed to illuminate that any non-zero constant equilibrium point must be not in the phase plane of dynamic system under Dirichlet zero boundary value, or it must lead to a contradiction. Next, under Lipschitz assumptions on active function, another example is designed to prove that the small diffusion effect will cause the essential change of the phase plane structure of the dynamic behavior of the delayed neural networks via a Saddle point theorem. Finally, a numerical example illustrates the feasibility of the proposed methods.

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe from normal-moderate neurodevelopmental outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation, had MR imaging at term-equivalent age, and neurodevelopmental testing at 18-24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors strongly predictive of outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean GA = 26.1±1.8 weeks, BW = 889.1±226.2 grams). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + ROP requiring surgery) had strong discriminatory power for severe disability (AUC=0.850), with a PPV of 76% and NPV of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit most from such services.

The present study aimed to develop a feeding strategy for pregnant sows which involved the prenatal administration of a mixture of pancreatic-like fungal enzymes, such as lipase, amylase, and protease, at (1) 1–115 days of gestation (group D1) and (2) 80–115 days of gestation (group D2) and to carry out a comparison with groups of sows that were not receiving such supplementation (negative control [NC] and positive control [PC]). It was found that the administration of the enzyme supplement resulted in a significant shortening of gestation (P ≤ 0.01). The pancreatic enzymes administered to sows had a significant effect on the number of liveborn piglets and weaned piglets, which was higher compared to the control groups that did not receive supplementation respectively: D1-12.1±1.1 and 11.12±1.1; D2- 12.8±1.3 and 11.75±0.07 vs. control groups KN-10.7±1.0 and 9.62±0,95 and KP 10.9±1.2 and 10.15±1.0 (P<0.006). Significant changes in piglet growth were observed after weaning up to 70 days of age. During this period, the most favorable growth parameters were found in groups D2 (420±91g) and PC (407±103g), in which piglets were given a mixture of pancreatic enzymes (lipase, amylase, and protease) at 3 weeks of age, and significantly higher weight gain and feed intake were observed compared to groups NC (378±114g) and D1 (381±96g) (P ≤ 0.007). In contrast, insulin levels were significantly lower in groups D1 and D2, respectively 6,8 IU/ml and 6,7 IU/ml compared to groups NC (14,6 IU/ml) and PC (16,6 IU/ml) ( (P ≤ 0.01). Piglets in group D2 had a significantly better feed conversion ratio (FCR) 1.604±0.10 compared to the other dietary groups: KN– 1.986±0.14; KP– 1.704±0.11; D1 – 1.932±0.15 (P ≤ 0.03). Histological imaging confirmed significantly thicker intestinal epithelium and intestinal mesenteron in animals from groups D2 and PC (P ≤ 0.03). Animals from the groups KP, D1 and D2 receiving enzymes showed a highly significant increase in the surface area of pancreatic follicles and pancreatic surface area compared to the group without KN supplementation (P<0.01). Furthermore, significantly higher activity of the brush border enzyme lactase was observed in groups D1; D2 and PC compared, respectively 32.90±3.99; 30.00±6.83 and 29.60±29.60 to group NC – 21.80± 3.27 (P ≤ 0.01).

Mitochondrial DNA copy number (mtDNAcn) is associated with mitochondrial function contributing various diseases. Understanding of the association between mtDNAcn and infant neurodevelopment, as well as the role of racial disparities, remains unknown. A cohort study was conducted with 55 preterm infants and a single blood sample was collected from each infant during their NICU stay to measure mtDNAcn. NICU Network Neurobehavioral Scale (NNNS) and Bayley Scale of Infant Developmental testing Edition III was assessed during NICU until 2 years of corrected age (CA). Linear regression models were performed to investigate the relationship between the clinical characteristics, neurobehavioral outcomes and mtDNAcn. Majority of our subjects were male, White, non-Hispanic, had C-section, and without preterm premature rupture of membrane (PPROM). Increased mtDNAcn was found associated with younger birth gestational age (GA), nonoptimal neurodevelopment. However, the opposite associations between mtDNAcn and neurodevelopmental outcomes were observed between Black and White infants up to 1 year of CA. Adverse early life experience, together with increased mtDNAcn in White infants, and decreased mtDNAcn in Black infants may be considered as significant positive predictors of poor early life neurodevelopmental outcomes in infants.

The centralized fusion estimation problem for discrete-time vectorial tessarine signals in multiple sensor stochastic systems with random one-step delays and correlated noises is analyzed under different T-properness conditions. Based on Tk, k=1,2, linear processing, new centralized fusion filtering, prediction, and fixed-point smoothing algorithms are devised. These algorithms have the advantage of providing optimal estimators with a significant reduction in computational cost compared to that obtained through a real or widely linear processing approach. Simulation examples illustrate the effectiveness and applicability of the algorithms proposed, in which the superiority of the Tk linear estimators over their counterparts in the quaternion domain is apparent.

In extant biology, biopolymers perform multiple crucial functions. The biopolymers are synthesized by enzyme-controlled biosystems that would not have been available at the earliest stages of chemical evolution and consist of correctly sequenced and/or linked monomers. Some of the abiotic “messy” polymers approximate some functions of biopolymers. Condensation polymers are an attractive search target for abiotic functional polymers since principal polymers of life are produced by condensation and since condensation allows for the accurate construction of high polymers. Herein the formation of hyperbranched polyesters that have been previously used in the construction of enzyme-like catalytic complexes is explored. The experimental setup compares between the branched polyesters prepared under mild continuous heating and the wet-dry cycle conditions. The results reveal that period wetting during which partial hydrolysis of the polyester occurs, helps control the chain growth and retards the gel transition. It is significant to the origin of life studies that environmental, prebiotically plausible conditions could achieve such control without enzymes or a skilled chemist. As expected in marginally controlled systems, the identification of each component of the heterogeneous system has proved challenging, but it is not crucial for drawing the conclusions.

Objective To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure. Method We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant. Results Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. Conclusion The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologist, and neonatal pediatricians.

To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure.We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant.Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologists and neonatal pediatricians.

Background: This study aimed to assess the impact of a nutrition-care bundle on growth and neurodevelopmental outcomes of micro-preterm infants born in a level III neonatal intensive care unit (NICU) by two years corrected age. Methods: A nutrition-care bundle emphasizing the prompt initiation of parenteral nutrition at birth, initiation of enteral feeds within 6 hours after birth, and early addition of human milk fortifiers was implemented in 2015 for infants born &lt;26 weeks gestation. This before-and-after study evaluated growth and neurodevelopmental outcomes in infants born between 2012-2013 (before-nutrition-bundle BNB) and 2016-2017 (after-nutrition-bundle ANB). Results: A total of 145 infants were included in the study. Infants in the ANB group (n=73) were smaller (birthweight and gestational age), and there were more male infants and multiples included compared to the BNB group (n=72). Enteral feeds and fortifiers started earlier in the ANB group. Growth velocity and weight-z-score changes were similar in both groups during NICU stay and post-discharge. Systemic steroid use, but not cohort, was linked to lower Bayley scores across all domains. Conclusions: Implementing a nutrition-care bundle was not consistently associated with improved weight-gain and neurodevelopmental outcomes in the micro-preterm infant population, likely due to ongoing high-quality nutritional care by the clinical team.

Background: Co-treatment of the fetal estrogen estetrol (E4) with androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) may further inhibit endocrine PCa tumor stimulators including testosterone (T), prostate-specific antigen (PSA), follicle-stimulating hormone (FSH), and insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study in advanced PCa patients requiring ADT (the PCombi study) was conducted to assess the effect of E4 co-treatment with LHRH agonist ADT on total T, free T, PSA, FSH, and IGF-1. Patients starting ADT were randomized 2:1 to 40 mg E4 (n=41) or placebo (n=21) for 24 weeks. Analyses were performed on the per-protocol population (PP), using the Wilcoxon-rank sum and the Kruskal-Wallis test. Results: The PP population consisted of 57 patients (37 ADT+E4; 20 ADT+placebo). All individual data of the four endocrine tumor stimulators are presented in figures in the paper and in supplementary tables, showing that E4 co-treatment almost completely suppressed FSH levels in all patients, on average by 98% versus 37% in the placebo group (p

Hemoglobin switch from fetal (HbF) to adult (HbA) has been studied intensively as an essential model for gene’s expression regulation, but also as a beneficial therapeutic approach for β-hemoglobinopathies, towards the objective of reactivating HbF. Transcription factor LRF (Leukemia/lymphoma-related), encoded from ZBTB7A gene has been implicated in fetal hemoglobin silencing, though has a wide range of functions that have not been fully clarified. We thus established LRF/ZBTB7A-overexpressing and ZBTB7A-knockdown K562 (human erythroleukemia cell line) clones and hemoglobin production was evaluated pre- and post-induction. Related effects on the process of hemoglobin switch from fetal to adult were also assessed. Transgenic K562 clones were further developed and studied under the influence of epigenetic chromatin regulators, such as DNA methyl transferase 3 (DNMT3) and Histone Deacetylase 1 (HDAC1), to evaluate LRF’s potential disturbance upon aberrant epigenetic background and provide valuable information of the preferable epigenetic frame, in which LRF unfolds its action on the β-type globin’s expression. ChIP-seq analysis demonstrated that LRF binds το γ-globin genes (HBG2/1) and apparently associates BCL11A for their silencing, but also, during erythropoiesis induction LRF binds BGLT3 gene promoting BGLT3-lncRNA production through the γ-δ intergenic region of β-type globin’s locus, triggering the transcriptional events from γ- to β-globin switch.

The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and identify decelerations and accelerations. These steps can potentially be automated and made more objective by data processing analysis, but training and evaluation datasets are required. Here, we describe a dataset of 155 FHR recordings in which a reference baseline, accelerations and decelerations have been annotated by expert consensus. 66 FHR recordings with a shared expert analysis have been included in a training dataset, and 90 other FHR recordings with a non-shared expert analysis have been included in an evaluation dataset. Researchers wishing to evaluate their automatic analysis method should submit their results for comparison with the expert consensus. The dataset also contains the results produced by 11 re-coded automatic analysis methods from the literature. All the data are available at http://utsb.univ-catholille.fr/fhr-review.

Objectives: The purpose of this study is to determine the association between umbilical venous blood flow (UVBF) to placental pulsatility index (PPI) ratio and gestational age (GA) in women undergoing prenatal assessments and adverse pregnancy outcome (APO) screening Methods: Between January and December 2022, sonographic examinations were conducted to assess the fetal umbilical cord insertion site in singleton fetuses, and hemodynamic indices of the umbilical artery, umbilical vein, and uterine artery were computed. Through regression analysis, we derived the optimal regression equation to elucidate the UVBF/PPI ratio parameters based on GA. Results: Among 492 singleton fetuses between 21+0 and 40+6 weeks of gestation in the final study. The average fetal UVBF/PPI ratio was 180.45±119.32. Correlation analysis revealed a positive relationship between the UVBF/PPI ratio and GA(p = .000). Using regression analysis, the best-fit regression equation was the linear function model, which explains the value of UVBF/PPI ratio parameters based on GA. Lower UVBF/PPI ratio revealed a positive relationship in the low birth weight fetuses (p=0.021) and higher preterm delivery rate (p=0.034). Cerebroplacental ratio (CPR) showed a high correlation with the UVBF/PPI ratio (r=0.471, p=0.000). Conclusions: The findings of our analyses revealed that contribute to our understanding of fetal hemodynamics and highlight the potential of UVBF/PPI ratio as a predictive marker for adverse pregnancy outcomes, such as preterm birth, low birth weight, or potential fetal hypoxemia. It might be useful for prenatal counseling and clinical purposes.

Introduction: Intrauterine fetal death (IFD) is death of fetus after the 20th week of gestation. Despite regular monitoring, the incidence of IFD remains high. This study aims to assess the incidence and risk factors for IFD in term pregnancies for better prevention and reduction of neonatal morbidity and mortality. Materials and Methods: A retrospective cohort study was conducted with term pregnant women diagnosed with IFD. The analysis included the number of deliveries, live births, and stillbirths. Statistical analysis involves descriptive and analytical statistical methods. Results: Average age was 30 years. Most patients had intermediate and high education, and one-third of patients had regular pregnancy monitoring. 53.33% were primiparous, and pregnancies occurred spontaneously. IFD mainly occurred in the 39th week of gestation. The average birth weight was approximately 3000g. 38.3% had one to two associated diseases, 5% more than three, and 56.7% were healthy. Recurrence of IFD was reported by 10% of patients, while 8.33% had a history of spontaneous abortion. Over 80% of placental histopathological findings indicated some pathology (infarction, infections, abruptio placenta). Conclusion: The most significant risk factors were pregnancy-induced hypertensive disorders, obesity, and diabetes, followed by hypothyroidism, maternal tachycardia, and anemia.

POGZ (Pogo transposable element derived with ZNF domain) is known to function as a regulator of gene expression. While variations in the POGZ gene have been associated with intellectual disabilities and developmental delays in humans, the exact pathophysiological mechanisms re-main unclear. To shed light on this, we created two lines of conditional knockout mice for Pogz, one specific to excitatory neurons (Emx1-Pogz mice) and the other to inhibitory neurons (Gad2-Pogz mice) in the brain. Emx1-Pogz mice showed a decrease in body weight, similar to total Pogz knockout mice. Although the two lines did not display significant morphological ab-normalities in the telencephalon, impaired POGZ function affected the electrophysiological prop-erties of both excitatory and inhibitory neurons differently. These findings suggest that these mouse lines could be useful tools for clarifying the precise pathophysiological mechanisms of neurodevelopmental disorders associated with POGZ gene abnormalities.

Abstract Background Pentraxin 3 (PTX3), an acute-phase protein associated with innate immunity, serves as a promising biomarker with diagnostic and prognostic value in preterm newborns. We aimed to investigate the relationship between PTX3 levels in neonates diagnosed with FIRS and early postnatal outcomes. Material and methods The study was designed as a prospective study. A total of 62 infants, 28–36 weeks of gestational age, were enrolled. During their neonatal intensive care unit (NICU) stay, the patients' mortality and morbidity outcomes were recorded and monitored. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral veins of neonates. The relationship between PTX3 concentrations and neonatal outcomes was investigated using non-parametric tests, regression analysis, and receiver operating characteristic (ROC) analysis. Results PTX3 levels in cord blood and peripheral blood samples of neonates were significantly associated with clinical conditions such as respiratory distress syndrome (RDS) (p = 0.022), sepsis (p = 0.001), neonatal pneumonia (p = 0.016), and FIRS (p = 0.001). In infants with FIRS, the increase in PTX3 was statistically significant (p = 0.013), with an OR of 1.131 (95% CI 1.026–1.246). The PTX3 level had a cutoff value >4.45 (p<0.001) for predicting FIRS with an AUC of 0.759, 76.9% sensitivity (95% CI 56.4–91), and 63.9% specificity (95% CI 46.2–79.2). Conclusions This study demonstrates that PTX3 shows potential as a sensitive and specific biomarker for the early diagnosis of FIRS in preterm newborns. PTX3 levels were significantly associated with clinical outcomes such as RDS, sepsis, neonatal pneumonia, and FIRS.

We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.

Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do not fully account for HbF variation. To investigate rare and common variants influencing HbF levels in SCD, we performed targeted next generation sequencing covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1. Results revealed a range of functionally relevant genetic variants. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletion in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. This study provides new insights in selecting essential variants associated with extreme HbF levels in SCD.

Deep hypothermic circulatory arrest (DHCA) is safe, but subtle neurodevelopmental deficits may persist far beyond the perioperative period. We investigated the relationship between DHCA duration and neurodevelopmental outcomes in young children undergoing cardiac surgery with DHCA. Children aged &lt; 42 months, including neonates who underwent cardiac surgery using DHCA without regional perfusion techniques, were included as the DHCA group. Children in the same age range undergoing cardiac surgery without DHCA were included as the control group. All patients underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development (BSTID) by a trained pediatrician. Seventeen of 25 DHCA and six of 10 control patients completed the BSTID assessment. The groups showed no preoperative, operative, or postoperative significant differences. In adjusted multivariable analysis, prematurity and age at assessment were significant changing predictors of each of the BSTID components (p &lt; 0.001), other than the gross motor component, where only age at assessment was a significant adjusting predictor. Longer DHCA was associated with lower fine and gross motor BSTID components; however, the association was not statistically significant (p = 0.06). Use of DHCA without regional perfusion techniques may be associated with less optimal neurodevelopmental outcomes if DHCA has a long duration.

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten, affecting approximately 1% of the global population and two million Americans. An increasing number of studies have identified a link between celiac disease and adverse maternal and fetal outcomes during pregnancy and after birth. Additionally, both celiac disease and pregnancy are associated with an increased risk for nutrient deficiencies, specifically vitamin B12 and folate. Deficiencies in these key nutrients are linked with several negative maternal and fetal health outcomes including preeclampsia, gestational diabetes, spontaneous abortion/miscarriage, preterm birth, NTDs, Intrauterine Growth Restriction, and low gestational age and birthweight. This review examines the current literature related to the folate trap and vitamin B12 deficiency in patients with celiac disease and pregnant women independently, and to provide rationale for future research to explore the correlation between the folate to B12 ratio in pregnant woman with celiac disease.

The objective of this study was to evaluate the potential benefits of feeding spray-dried porcine plasma (SDPP) to pigs infected with African swine fever virus (ASFV). Two groups of twelve weaned pigs each were fed with CONVENTIONAL or 8% SDPP enriched diets. Two pigs (trojans)/group) were injected intramuscularly with the pandemic ASFV (Georgia 2007/01) and comingled with the rest of the pigs (1:5 trojan:naïve ratio) to simulate a natural route of transmission. Trojans developed ASF and died within the first week after inoculation but contact pigs did not develop ASF, viremia or seroconversion. Therefore, three more trojans per group were introduced to optimize the ASFV transmission (1:2 trojan:naïve ratio). Blood, nasal and rectal swabs were weekly harvested and at end of the study, ASFV-target organs collected. After the second exposure, rectal temperature of conventionally fed contact pigs increased >40.5˚C while fever was delayed in the SDPP contact pigs. Additionally, PCR Ct values in blood, secretions and tissue samples were significantly lower (P<0.05) for CONVENTIONAL compared to SDPP contact pigs. Under these study conditions, contact exposed pigs fed SDPP had delayed ASFV transmission and reduced virus load, likely by enhanced specific T-cell priming after the first ASFV-exposure.

The effect of CO2 pre-treatments on tomato quality prior to cold storage was investigated using physiochemical and transcriptome changes. Three hours CO2 treated fruits were firmer than untreated fruits and had a good appearance even after being transferred from 4°C storage to 20°C for 8 d. CO2 pretreatment with cold storage showed a synergistic effect on delayed ripening through reduced respiration; these tomatoes exhibited a lower lycopene content than untreated fruit under cold storage. Tomatoes treated with 30% CO2 had fewer pits than untreated fruits subjected to chilling temperatures, even after being transferred to 20°C for 8 d. Functional enrichment analyses from transcriptome and metabolome commonly showed that CO2-responsive genes or metabolites were involved in the sucrose and starch and biosynthesis of secondary metabolisms. The most frequently detected domain, ethylene-responsive factor domain and reduced glycolysis provide insights into the mechanism that CO2 regulates tomato quality.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Maternal hyperglycemia, induced by gestational diabetes mellitus (GDM), has detrimental effects on fetal vascular development, ultimately increasing the risk of cardiovascular diseases in offspring. The potential underlying mechanisms by which these complications occur are through functional impairment and epigenetic changes in fetal endothelial progenitor cells (EPCs), however, remain less defined. We confirm that intrauterine hyperglycemia leads to impaired angiogenic function of fetal EPCs, as observed through functional assays of outgrowth endothelial cells (OECs) derived from fetal EPCs of GDM pregnancies (GDM-EPCs). Notably, PCDH10 expression is increased in OECs derived from GDM-EPCs, which is associated with the inhibition of angiogenic function in fetal EPCs. Additionally, increased PCDH10 expression is correlated with hypomethylation of the PCDH10 promoter. Our findings demonstrate that in utero exposure to GDM can induce angiogenic dysfunction in fetal EPCs through altered gene expression and epigenetic changes, consequently increasing the susceptibility to cardiovascular diseases in offspring of GDM mothers.

Sickle cell disease (SCD) is a pathophysiological condition of chronic hemolysis, oxidative stress, and elevated inflammation. The transcription factor Nrf2 is a master regulator of oxidative stress. Here we reported that the FDA-approved, oral agent simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A reductase, significantly activates the expression of Nrf2 and antioxidant enzymes. Simvastatin also induces fetal hemoglobin expression in SCD patient erythroid progenitors and a transgenic mouse model. Simvastatin alleviates SCD symptoms by decreasing hemoglobin S sickling, oxidative stress, and inflammation stress in erythroblasts. Particularly, simvastatin increases cellular levels of cystine, the precursor for the biosynthesis of antioxidant reduced glutathione and decreases the iron content in SCD mouse spleen and liver tissues. Mechanistic studies suggest that simvastatin suppresses the expression of critical histone methyltransferase, Enhancer of zeste homolog 2 to reduce both global and gene-specific histone H3 lysine 27 trimethylation. These chromatin structural changes promote the assembly of transcription complexes to fetal γ-globin and antioxidant genes regulatory regions, in an antioxidative response element-dependent manner. In summary, our findings suggest that simvastatin activates fetal hemoglobin and antioxidant protein expression and modulates iron and cystine/reduced glutathione levels to improve the phenotype of SCD and represents a therapeutic strategy for further development.

Gut microbiota plays a critical role in physiological regulation throughout life and is specifically modified to meet the demands of individual life stages and during pregnancy. Maternal gut microbiota is uniquely adapted to the pregnancy demands of the mother and the developing fetus. Both animal studies in pregnant germ-free rodents and human studies have supported a critical association between the composition of maternal microbiota during pregnancy and fetal development. Gut microbiota may also contribute to the development of the fetal gut-brain axis (GBA), which is increasingly recognized for its critical role in health and disease. Most studies consider birth as the time of GBA activation and focus on postnatal GBA development. This review focuses on GBA development during the prenatal period and the impact of maternal gut microbiota on fetal GBA development. It is hypothesized that adaptation of maternal gut microbiota to pregnancy is critical for the GBA prenatal development and maturation of GBA postnatally. Consequently, factors affecting maternal gut microbiota during pregnancy, such as maternal obesity, diet, stress and depression, infection, and medication, also affect fetal GBA development and are critical for GBA activity postnatally. Altered maternal gut microbiota during gestation has been shown to have long-term impact postnatally and multigenerational effects. Thus, understanding the impact of maternal gut microbiota during pregnancy on fetal GBA development is crucial for managing fetal, neonatal, and adult health, and should be included among public health priorities.

Cumulative exposure to multiple early life stressors are expected to affect behavioral development causing increased susceptibility towards neuropsychiatric disorders. The present study was designed to mimic such conditions in rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n=32; 140-150 gm) were switched to low protein (LP; 8% protein) or Control (20% protein) diet, 15 days prior to conception and then diet regime was maintained throughout the experimental period. Pups born to Control and LP dams were intraperitoneally injected with deltamethrin (DLT-pyrethroid insecticide; 0.7mg/kg body weight; PND 1 to 7) or lipopolysaccharide (LPS-bacterial endotoxin; 0.3mg/kg body weight; PND 3 and 5) or DLT+LPS, on designated days forming 8 experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by Open field, Elevated plus maze, Light and Dark box, and Rotarod tests. LP rats were found to be more susceptible to either singular or cumulative exposure as compared to their age matched control counterparts, showing significantly severe behavioural abnormalities, as hyperactivity, attention deficits, impulsiveness and low anxiety, the hallmark symptoms of neuropsychiatric disorders like schizophrenia and ADHD, suggesting thereby that early life multi-hit exposure may predispose individuals to developmental disorders.

The widely conserved RACK1 protein is a WD-40 type scaffold protein that regulates diverse environmental stress signal transduction pathways. Arabidopsis RACK1A has been reported to interact with various proteins in salt stress and Light-Harvesting Complex (LHC) pathways. However, the mechanism of how RACK1 contributes to the photosystem and chlorophyll metabolism in stress conditions remains elusive. Using T-DNA-mediated activation tagging transgenic rice (Oryza sativa L.) lines, we show that leaves from rice RACK1B gene (OsRACK1B) gain-of-function (RACK1B-OX) plants exhibit the stay-green phenotype under salinity stress. In contrast, leaves from down-regulated OsRACK1B (RACK1B-UX) plants display an accelerated yellowing. qRT-PCR analysis revealed that several genes encoding chlorophyll catabolic enzymes (CCEs) are differentially expressed in both RACK1B-OX and RACK1B-UX rice plants. In addition to CCEs, STAY-GREEN (SGR) is a key component that forms the SGR-CCE complex in senescing chloroplasts, which causes LHCII complex instability. Transcript and protein profiling revealed a significant upregulation of OsSGR in RACK1B-UX plants than that in RACK1B-OX rice plants during salt treatment. The results imply that senescence-associated transcription factors (TFs) are altered in accordance with altered OsRACK1B expression, indicating a transcriptional reprogramming by OsRACK1B and a novel regulatory mechanism involving the OsRACK1B-OsSGR-TFs complex. Our findings suggest that ectopic expression of OsRACK1B negatively regulates chlorophyll degradation, leads to the steady level of LHC-II isoform Lhcb1, an essential prerequisite for the state transition of photosynthesis for adaptation, and delays salinity-induced senescence. Taken together, these results provide important insights into the molecular mechanisms of salinity-induced senescence, which can be useful in circumventing the effect of salt on photosynthesis and in reducing the yield penalty of important cereal crops, like rice, in global climate change conditions.

Abstract: Fetal Alcohol Spectrum Disorder (FASD) is considered a lifelong disability that has been framed by neurobiological descriptions focused on the brain. These are important features but fail to tell the story of living with FASD. By surveying those with FASD, this work expands upon prior survey work which illustrated a multitude of early onset physiological issues occurring at rates much higher than typical of the general population. The current project, again using an anonymous survey methodology, seeks to open up other direct experiences to better understand the complexity of living with FASD. An anonymous online survey was used to gather data on advresity in childhood, schooling, employment, housing and finances, involvement with the criminal justice system as well as relationships and parenting. Results inform how supports can be enhanced and targeted with a goal of improving the quality of life. The survey was developed by adults living with FASD who have served as a long-standing advocacy and educational group influencing policy and practice in the field.

Doppler findings of persistent reverse end-diastolic flow (PREDF) in a fetal middle cerebral artery (MCA) are a very rare sonographic finding and are a marker of poor fetal condition. This finding often leads to intrauterine fetal death or early neonatal death. The reverse end-diastolic flow in the middle cerebral artery is the terminal hemodynamic event. Fetal cerebral circulation normally has a high impedance; in the event of fetal hypoxemia, impedance decreases, resulting in the central redistribution of blood flow to vital organs, which maintains the oxygen delivery to the brain. Reverse flow in the middle cerebral arteries describes the loss of this autoregulatory process. PREDF is a sequence happening due to increased extracranial or intracranial pressure. Previous case reports mentioned intracranial hemorrhage, intrauterine growth restriction (IUGR), fetal anemia, and fetal hepatic abnormalities as leading problems to PREDF. This condition presumably arises due to cerebral edema associated with severe hypoxemia. We reported Doppler findings of PREDF MCA in a 33-year-old female at 30 weeks gestation who was referred to the hospital with severe preeclampsia accompanied by IUGR and oligohydramnios. A cesarean section was performed due to severe preeclampsia and a low bishop score. Hypotheses on various etiologies and their association with intrauterine/neonatal death as well as the best management still require further investigation.

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥ 1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, β-HCG, and HbA1C was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with increase in β-HCG and HbA1C, and decrease of total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSD), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role of immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.