Etiological Analysis of Neurodevelopmental Disabilities: Single-Center Eight-Year Clinical Experience in South China

Etiology determination of neurodevelopmental disabilities (NDDs) currently remains a worldwide common challenge on child health. We herein reported the etiology distribution feature in a cohort of 285 Chinese patients with NDDs. Although concrete NDD etiologies in 48.4% of the total patients could not be identified, genetic diseases (with the proportion of 35.8% in the total cases) including inborn errors of metabolism (IEM) and congenital dysmorphic diseases, constituted the commonest etiology category for NDDs in this study. The two key experimental technologies in pediatric metabolomics, gas chromatography-mass spectrometry (GC-MS), and tandem mass spectrometry (MS-MS), proved to be substantially helpful for the exploration of the NDD etiologies in this clinical investigation. The findings in this paper provided latest epidemiologic information on the etiology distribution of NDDs in Chinese, and the syndromic NDDs caused by citrin deficiency and the novel chromosomal karyotype, respectively, further expanded the etiology spectrum of NDDs

A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus

IntroductionRecombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes.MethodsIn this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively.ResultsWe found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors.DiscussionOur findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies

Paternal Body Mass Index (BMI) Is Associated with Offspring Intrauterine Growth in a Gender Dependent Manner

Background: Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results: We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn’s body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only

An Energy Efficient Load Balancing Tree-Based Data Aggregation Scheme for Grid-Based Wireless Sensor Networks

A wireless sensor network (WSN) consists of a very large number of sensors which are deployed in the specific area of interest. A sensor is an electronic device equipped with a small processor and has a small-capacity memory. The WSN has the functions of low cost, easy deployment, and random reconfiguration. In this paper, an energy-efficient load balancing tree-based data aggregation scheme (LB-TBDAS) for grid-based WSNs is proposed. In this scheme, the sensing area is partitioned into many cells of a grid and then the sensor node with the maximum residual energy is elected to be the cell head in each cell. Then, the tree-like path is established by using the minimum spanning tree algorithm. In the tree construction, it must meet the three constraints, which are the minimum energy consumption spanning tree, the network depth, and the maximum number of child nodes. In the data transmission process, the cell head is responsible for collecting the sensing data in each cell, and the collected data are transmitted along the tree-like path to the base station (BS). Simulation results show that the total energy consumption of LB-TBDAS is significantly less than that of GB-PEDAP and PEDAP. Compared to GB-PEDAP and PEDAP, the proposed LB-TBDAS extends the network lifetime by more than 100%. The proposed LB-TBDAS can avoid excessive energy consumption of sensor nodes during multi-hop data transmission and can also avoid the hotspot problem of WSNs

A Functional Fetal HSD11B2[CA]n Microsatellite Polymorphism is Associated with Maternal Serum Cortisol Concentrations in Pregnant Women

Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding (gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration (R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA]n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women

Printed Three-dimensional Anatomic Templates for Virtual Preoperative Planning Before Reconstruction of Old Pelvic Injuries: Initial Results

Background: Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy, difficult-to-access surgical sites, and the relatively low incidence of such cases. Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture. The goal of this study was to assess the use of three-dimensional (3D) printing techniques for surgical management of old pelvic fractures. Methods: First, 16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data. Next, nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models. The pelvic injuries were all type C, and the average time from injury to reconstruction was 11 weeks (range: 8-17 weeks). The workflow consisted of: (1) Printing patient-specific bone models based on preoperative computed tomography (CT) scans, (2) virtual fracture reduction using the printed 3D anatomic template, (3) virtual fracture fixation using Kirschner wires, and (4) preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation. These models aided communication between surgical team members during the procedure. This technique was validated by comparing the preoperative planning to the intraoperative procedure. Results: The accuracy of the 3D printed models was within specification. Production of a model from standard CT DICOM data took 7 hours (range: 6-9 hours). Preoperative planning using the 3D printed models was feasible in all cases. Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases. The patients were followed for 3-29 months (median: 5 months). The fracture healing time was 9-17 weeks (mean: 10 weeks). No delayed incision healing, wound infection, or nonunions occurred. The results were excellent in two cases, good in five, and poor in two based on the Majeed score. Conclusions: The 3D printing planning technique for pelvic surgery was successfully integrated into a clinical workflow to improve patient-specific preoperative planning by providing a visual and haptic model of the injury and allowing patient-specific adaptation of each osteosynthesis implant to the virtually reduced pelvis

Multivariable regression analysis of the association between ultrasound measurements in late gestation or birth weight and paternal BMI in newborn girls.

<p>Different regression models showing the association between ultrasound measurements in late gestation or birth weight and paternal BMI in newborn girls. Shown are the T, B and P-values for paternal BMI. B: non-standardized regression coefficient.</p><p>Model A: multivariable regression analyses was done in all cases considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal glycated serum protein, parity and eithergestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding factors.</p><p>Model B: multivariable regression analyses was done excluding cases where fathers had hypertension but considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding factors.</p><p>Model C: multivariable regression analyses was done in all cases considering maternal BMI, hypertension during pregnancy, maternal glycated serum protein, and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding factors.</p><p>B: partial regression coefficient; 95% CI: 95% confidence interval for B; T: standardized regression coefficient.</p

Biometric data of the newborns (n = 899) data of the newborns (n = 899).

<p>Data are given as mean ± SD or absolute numbers.</p