New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Development of a chronic compression spinal cord injury model in neonatal and adult rats

Background:Spinal cord injury presents a significant burden globally,with traumatic spinal cord injury being the predominant cause historically.However,nontraumatic spinal cord injury(NTSCI)is emerging as a significant contributor,particularly in devel-oped nations,yet it remains poorly understood due to underreporting and misclassifi-cation.NTSCI,spanning various etiologies such as bony growths,vascular conditions,infections,neoplastic conditions,and immune disorders,poses unique challenges in diagnosis and treatment,often resulting in lifelong morbidity.This study addresses the lack of suitable animal models for NTSCI research,especially in neonatal animals.Methods:Utilizing a solid spacer approach,we developed a compression NTSCI model applicable to both neonatal and adult Sprague-Dawley rats.Results:Through anatomical measurements and in vivo experiments,we confirmed the feasibility and safety of the spacer insertion procedure and observed no acute off-target effects.Conclusion:The versatility of this model lies in its adaptability to different ages of rats,offering a cost-effective and reproducible means to induce graded injuries.Moreover,behavioral assessments demonstrated observable hindlimb function,validating the model's utility for studying functional outcomes.Although challenges persist,par-ticularly in accounting for spinal column growth in neonatal animals,this model fills a crucial gap in pediatric NTSCI research.By providing a platform to investigate patho-physiological mechanisms and test potential treatments,it offers promising avenues for advancing our understanding and management of pediatric NTSCI.

Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.

Development of a Three-Dimensional Measuring System for Neonates' Head and Facial Morphology

A web camera based multi-camera convergent close-range photogrammetric system is developed to obtain the neonates＇ head and facial morphology. The data will then be used to develop a secure and good-fitting eye-patch protector for neonates, particularly whoa they are exposed to bright lights such as phototherapy light. Measurements obtained by the system are evaluated and validated against data obtained from optical scanning. Results show that the photogrammetric system meets the requirements of measuring accuracy and safety for neonate in the neonatal units.

Lead level in foremilk and neurobehavioral development of neonates

BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neurobehavioral development of neonates taking lead level in foremilk as lead exposure index. DESIGN： A controlled observation. SETTING： Maternal and Child Health Center, Shanxi Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history. The corresponding puerperants were aged （27 ±5 ）years. They had no various acute and chronic diseases during pregnancy, and family history of neurological disease as well as occupational lead exposure. Informed consents of detected items were obtained from the puerperants. METHODS： ①Determination of lead level in foremilk- Altogether 128 foremilk samples, 1 mL each, were collected between January and February 2005. The same amount of violet acid was added to each sample. After foremilk was fully dissolved, 0.2 mL solution was taken for determining lead level with atomic absorption spectrometer in graphite stove. The determined process strictly followed the internal quantity control of laboratory and was involved in the blind quality control of Institute of Environmental Health of Chinese Academy. ②Participants grouping： Totally 128 neonates were involved, and the normal reference value of lead level of foremilk was 0.06 - 0.48 μ mol/L. The involved neonates were assigned into high-level lead group （≥ 0.24 μ mol/L, n =60） and low-level lead group （〈 0.24 μ mol/L, n =68）. ③Assessment of neurobehavioral development of neonates： Neurobehavioral development level of neonates who was born 24 to 72 hours was assessed with 20-item neonatal neurobehavioral determination method, which involved behavioral ability （6 items）, passive muscular tension （4 items）, active muscular tension （4 items）, primitive reflection （3 items） and general evaluation （3 items）. Each above-mentioned scoring had 3 scales （0,1 and 2 points）. The full mark of 20 items was 40 points. Neurological behaviors of neonates might be unabnormal when scoring was 〈 35 points. OUTCOME MEASURES： Assessment results of neurobehavioral development of neonates in high- and low-level lead neonates. RESULTS： After lead-level determination, the involved neonates in two groups participated in the final analysis. Neurobehavioral total scores of neonates of high-level lead group were lower than those in the low-level lead group [ （35.9±1.3 ） points vs. （37.7 ±1.4） points, P 〈 0.01 ]. The scores of neonatal erection in high-level lead group were lower than those in low-level lead group [ （ 1.4±0.4） points vs. （ 1.8 ±0.5 ） points, P 〈0.01], and time for head erection of neonates in the high-level lead group was shortened as compared with that in the low-level lead group [ （1.8±1.7） minutesvs. （3.3±2.2） minutes, P〈0.01]. CONCLUSION： 0.24 μ mol/L lead level in foremilk has certain relationship with neurobehavioral development. The main influenced manifestations are shortened duration of neonatal head erection and actively contracted extensor, i.e. cervical curved ability is weakened.

Evaluation of Perinatal and Developmental Outcomes in Neonates with Abstinence Syndrome Admitted to NICU

Drug abuse by pregnant women is one of the significant problems for mothers and their neonates.This study aimed to investigate the effects of maternal substance use disorder during pregnancy on neonatal developmental criteria.In a case-control study,clinical records of 90 neonates diagnosed with neonatal abstinence syndrome who were admitted to NICU in one of four hospitals affiliated with Shahid-Beheshti University of Medical Sciences in Tehran,Iran between 2017 and 2020 were compared to 90 neonates without neonatal abstinence syndrome(control group).Demographic information and data for neonatal developmental characteristics and complications were extracted from the clinical records of this convenience sample.Data for the type and method of maternal substance use during pregnancy were collected through a telephone call with mothers.Our data showed that the prevalence of drug addiction was 1.8%among pregnant women,and the most common drugs used by mothers were opium(n=45%,50%),amphetamine(n=30%,33%),and methadone(n=14%,16%).Neonates with abstinence syndrome had a higher prevalence of transient tachypnea of the newborn(TTN)(P=0.004),and a prevalence of being admitted to NICU(P=0.05)and for a longer duration(P<0.001).Their mothers had a higher prevalence of having pre-eclampsia(P=0.010).Using morphine vs.amphetamine showed no difference based on their effects on mothers and neonates.Substance use during pregnancy increased the prevalence of pregnancy complications(pre-eclampsia)and neonatal complications(TTN and prevalence and duration of hospitalization).Therefore,planning for the development of health policies to raise awareness among women and more broadly,all members of the community,is important to prevent the tendency to engage in this potentially high-risk behavior.

Amino acids and mammary gland development:nutritional implications for milk production and neonatal growth

Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

Association of Insulin-like Growth Factors with Lung Development in Neonatal Rats

To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF-Ⅰ, -Ⅱ (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF-Ⅰ in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-Ⅰ during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-Ⅰ was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-Ⅱ took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-Ⅱ in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-Ⅰ, -Ⅱ mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-Ⅰ, -Ⅱ and lung development in newborns. The IGF-Ⅱ works at early stage and the that of IGF-Ⅰ works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

Effects of Neonatal Undernutrition on Development of the Dorsolateral Prefrontal Cortex Pyramidal Cells in the Rat

The dorsolateral prefrontal cortex (dlPFC) of the rat plays a role in the encoding of neuronal signals involved in conflict-induced behavioral adjustment, working memory, planning and executive abilities, attentional control and other cognitive responses. In altricial species, early perinatal undernutrition interferes with the morphofunctional organization of a number of central nervous system (CNS) structures including the prefrontal cortex. The effects of neonatal undernutrition on dendritic arbor density, perikaryon measurements, and the number of spines (detected by rapid-Golgi) of basilar dendritic segments in layer III pyramidal neurons of the dlPFC were examined in male Wistar rats on postnatal (PDs) 12, 20, and 30. In the underfed (U) subjects the distal portions of the dendritic arbors had a consistent hipoplasia, mainly on PD 30, with reduced cross sectional area, perimeter, and spine densities on the basilar dendrites on all days studied. Thus, the alterations of the dlPFC pyramidal neurons may interfere with the plastic synaptic activity and cognitive performance of rats subjected to the stress of early underfeeding. Characterizing these anatomical alterations may help to understand the disrupted cognitive processes associated with neonatal undernutrition.

Surgical Repair of Ventricular Septal Defect in Neonates: Indications and Outcomes

Background:The optimal surgical timing and clinical outcomes of ventricular septal defect(VSD)closure in neo-nates remain unclear.We aimed to evaluate the clinical outcomes of VSD closure in neonates(age≤30 days).Methods:We retrospectively reviewed 50 consecutive neonates who underwent VSD closure for isolated VSDs between August 2003 and June 2021.Indications for the procedure included congestive heart failure/failure to thrive and pulmonary hypertension.Major adverse events(MAEs)were defined as the composite of all-cause mortality,reoperation,persistent atrioventricular block,and significant(≥grade 2)valvular dysfunction.Results:The median age and body weight at operation were 26.0 days(interquartile range[IQR],18.8–28.3)and 3.7 kg(IQR,3.3–4.2),respectively.The median follow-up duration was 110.4 months(IQR,56.8–165.0).Seven patients required preoperative respiratory support,andfive had significant(≥grade 2)preoperative valvular dysfunction.One early mortality occurred due to irreversible cardiogenic shock;no late mortality was observed.One reopera-tion was due to hemodynamically significant residual VSD at 103.8 months postoperatively.The overall survival,freedom from reoperation,and freedom from MAE at 15-years were 98.0%,96.3%,and 94.4%,respectively.Pre-operative mechanical ventilation was associated with a longer duration of postoperative mechanical ventilation(p<0.001)and a longer length of intensive care unit stay(p<0.001).Conclusions:VSD closure with favorable outcomes without morbidities is feasible even in neonates.However,neonates requiring preoperative respiratory support may require careful postoperative management considering the long-term postoperative risks.Overall,surgical VSD closure might be indicated earlier in neonates with respiratory compromise.

Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats

Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-related behaviors. In this study, Sprague-Dawley rats were purchased from the Animal Center of Anhui Medical University of China. For the experiments in the adult stage, rats were intraperitoneally injected with calpeptin, 2 mg/kg, once a day, on postnatal days 7–14. Then on postnatal day 60, the Morris water maze test was used to evaluate spatial learning and memory abilities. The open field test was carried out to assess anxiety-like activities. Phalloidin staining was performed to observe synaptic morphology in the hippocampus. Immunohistochemistry was used to count the number of NeuN-positive cells in the hippocampal CA1 region. DiI was applied to label dendritic spines. Calpeptin administration impaired spatial memory, caused anxiety-like behavior in adulthood, reduced the number and area of apical dendritic spines, and decreased actin polymerization in the hippocampus, but did not affect the number of NeuN-positive cells in the hippocampal CA1 region. For the neonatal experiments, neonatal rats were intraperitoneally injected with calpeptin, 2 mg/kg, on postnatal days 7 and 8. Western blot assay was performed to analyze the protein levels of Akt, Erk, p-Akt, p-Erk1/2, Erk1/2, SCOP, PTEN, mTOR, p-mTOR, CREB and p-CREB in the hippocampus. SCOP expression was increased, and the phosphorylation levels of Akt, mTOR and CREB were reduced in the hippocampus. These findings show that calpeptin administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function. Therefore, calpeptin administration after birth is a risk factor for neurodevelopmental defects.

Prevalence and outcomes of neonates with severe COVID-19:An observational study at Children’s Hospital 1 in Ho Chi Minh City,Vietnam

Objective:To evaluate the impact of the severe COVID-19 pandemic on neonates and develop strategies to improve their outcomes.Methods:We conducted an observational cross-sectional study at Children's Hospital 1(CH1)from July 25,2021,to May 31,2022.All neonates who had fever or respiratory symptoms or were born from mothers with COVID-19 and had a positive RT-PCR SARS-CoV-2 result would be included.We classified neonates with COVID-19 into 2 groups:mild/moderate and severe for analysis.Differences between groups were analyzed using Fisher's exact test/Chi-square test for categorical variables and Student's t-test/Wilcoxon Rank Sum test for continuous variables.Results:This study included 88 newborns who had positive RT-PCR SARS-CoV-2 results.The severity COVID-19 rate among neonatal cases was found to be 13.6%(12/88),with a corresponding mortality rate of 1.1%(1/88).All severe cases showed lung abnormalities as evident on chest X-ray images.In addition to respiratory symptoms,a higher incidence of gastrointestinal manifestations,such as vomiting and diarrhea,was observed in the severe group,indicating a compelling association.The administration of anticoagulant and anti-inflammatory drugs in the study group resulted in a satisfactory outcome with no significant complications.Conclusions:The COVID-19 pandemic has had a substantial impact on the well-being of neonates.The management of COVID-19 in this population presents significant challenges.

Analysis of TORCH results of retinal exudative changes in neonates

AIM:To explore the relationship between retinal exudative changes in neonates and perinatal toxoplasmosis,others,rubella,cytomegalovirus,and herpes simplex virus(TORCH)infections,as well as the characteristics of TORCH infection in neonates with retinal exudative changes.METHODS:Retrospective study.A total of 612 neonates with retinal exudative changes detected during ophthalmic screening in our hospital from May 2019 to March 2023 were selected.TORCH tests were performed on these neonates,and the results were subjected to statistical analysis to determine the infection characteristics.The neonates with retinal exudative changes were grouped by sex and age,the characteristics of TORCH infection were analyzed,and the positive rates were compared.RESULTS:Among the 612 neonates with retinal exudative changes,the highest positive rate was observed for cytomegalovirus(CMV-IgG)(96.7%),followed by rubella virus(RV-IgG)(73.9%).Mixed infections with two or three viruses were also observed,with the highest positive rate for mixed infection of RV-IgG and CMV-IgG reaching 71.2%.There was no statistically significant difference in TORCH infection among neonates of different sex(P>0.05).However,there were statistically significant differences in RV-IgG and CMV-IgM infections with retinal exudative changes among neonates of different age groups(P<0.05).CONCLUSION:Perinatal TORCH infection may be an important factor causing retinal exudative changes in neonates.The differences in various infections are not related to sex but are related to different age groups.

Evaluation of Procedural Pain in Neonates in Cameroon

Introduction: Acute pain associated with caregiving is a major cause of pain among neonates. Left untreated, it can lead to long-term neurosensory and psychoaffective consequences. In Cameroon, this subject has been scarcely explored, thus constituting an impediment to the management of care-induced pain. Objective: Assess procedural pain in neonates in Yaoundé. Material and Methods: We conducted a cross sectional study with prospective data collection over a period of eight months (October 2022 to May 2023) in three hospitals. We included neonates who were being cared for and were not crying prior to the onset of healthcare, whose parents consented to the study. Assessments were done using the DAN scale, which is specific to care-induced pain. Data was entered and analyzed using SPSS 23.0 software. Results: A total of 161 newborns were included. The hospital prevalence of care-induced pain in neonates was 85%. Neonatal sepsis was the main cause for admission (96.6%). The most common procedures were venous blood sampling (94.4%) and insertion of peripheral venous lines (93.8%). The pain intensity for these procedures was severe (83.9%). The most painful procedure was lumbar tap, followed by venous access procedures. Conclusion: Neonates in hospitals are subjected to many painful procedures. The pain experienced during these procedures is severe. The most nociceptive procedure is a lumbar puncture.