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Background Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. Results We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected. Loss of NKT cells is cell intrinsic and not due to an insufficient selection environment. The absence of NKT cells in UTX/JMJD3-deficient mice protects mice from concanavalin A‐induced liver injury, a model of NKT‐mediated hepatitis. GO‐analysis of RNA-seq data indicates that cell cycle genes are downregulated in UTX/JMJD3-deleted NKT progenitors, and suggest that failed expansion may account for some of the cellular deficiency. The phenotype appears to be demethylase‐dependent, because UTY, a homolog of UTX that lacks catalytic function, is not sufficient to restore their development and removal of H3K27me3 by deletion of EZH2 partially rescues the defect. Conclusions NKT cell development and gene expression is sensitive to proper regulation of H3K27 methylation. The H3K27me3 demethylase enzymes, in particular UTX, promote NKT cell development, and are required for effective NKT function.

Excessive accumulation of reactive oxygen species (ROS) is one of the reasons for the slow growth of mammalian preimplantation embryos. Peroxisome proliferators-activated receptor gamma (PPARγ) functions in the nuclear regulatory factor 2 (Nrf2) antioxidant pathways by binding to the promoters of antioxidant genes and regulates the expression of genes that associate with NADPH oxidase. To understand the role of PPARγ in the development of early embryos and define the mechanism responsible for the arrest in development during the maternal-to-zygotic transition (MZT), we used an embryo model of oxidative damage by H2O2. We found that H2O2 exposure significantly decreased embryo development, increased the intracellular ROS level, and upregulated the expression levels of the NADPH oxidase genes NOX2, DUOX1, and NOXA1. By contrast, embryo treatment with pioglitazone after H2O2 exposure promote embryo development, significantly decreased the ROS level, downregulates the expression levels of NOX2, DUOX1, and NOXA1, and upregulated the expression levels of PPARγ, Nrf2, and the antioxidant enzyme genes GPx3, GPx4, SOD1, SOD2, and SOD3. In conclusion, pioglitazone can reduce intracellular oxidative stress during in vitro development by promoting the expression of antioxidant genes and suppressing the expression of NADPH oxidant genes.

Background Rat pre-implantation embryos often suffer 2-cell stage developmental arrest and fail to progress further under in-vitro conditions. Objective In order to understand underlying mechanism leading to 2-cell arrest, we investigated the molecular changes, culture conditions and subcellular changes. Methods Gene expression in in-vivo developed 2-cell embryos (in-vivo), in- vitro developed 2-cell embryos (in-vitro), and in-vitro 2-cell arrested embryos (arrested) were investigated using microarrays and real-time PCR. Ultra-structural changes were determined using electron microscopy. Results Gene expression was similar between in-vivo and in-vitro embryos. Over 2400 genes changed in arrested embryos compared to in-vivo and in-vitro embryos. The mRNAs encoding proteins involved in translation were elevated in arrested embryos. In-vivo and in-vitro embryos highly expressed genes that were involved in cell cycle, and protein catabolic process compared to arrested embryos. Gene expression data suggested subcellular changes associated with 2-cell block. Transmission electron microscopy showed that in-vivo embryos had healthy subcellular structure, whereas arrested embryos did not have a nuclear membrane, contained small mitochondria and autophagic vacuoles. Furthermore, gene expression data was used for the optimization of culture media conditions to obtain better in-vitro embryonic development. Comparison of five and 20 % oxygen in culture resulted in two times more blastocyst formation with 5 % oxygen. Conclusions These results showed that although all experimental groups appeared morphologically similar, arrested embryos had ultra-structural and molecular changes associated with oxidative stress and apoptosis. In-vitro culture under low oxygen and media additives reduced 2-cell block in rat embryos.

The embryonic developmental block occurs at the 8-cell stage in cattle and is characterized by a lengthening of the cell cycle and an increased number of embryos that stop development. The maternal-embryonic transition arises at the same stage resulting in the transcription of many genes. Gene expression studies during this stage may contribute to the understanding of the physiological mechanisms involved in the maternal-embryonic transition. Herein we identified genes differentially expressed between embryos with high or low developmental competence to reach the blastocyst stage using differential display PCR. Embryos were analysed according to developmental kinetics: fast cleavage embryos showing 8 cells at 48 h post insemination (hpi) with high potential of development (F8), and embryos with slow cleavage presenting 4 cells at 48 hpi (S4) and 8 cells at 90 hpi (S8), both with reduced rates of development to blastocyst. The fluorescence DDPCR method was applied and allowed the recovery of 176 differentially expressed bands with similar proportion between high and low development potential groups (52% to F8 and 48% in S4 and S8 groups). A total of 27 isolated fragments were cloned and sequenced, confirming the expected primer sequences and allowing the identification of 27 gene transcripts. PI3KCA and ITM2B were chosen for relative quantification of mRNA using real-time PCR and showed a kinetic and a time-related pattern of expression respectively. The observed results suggest the existence of two different embryonic genome activation mechanisms: fast-developing embryos activate genes related to embryonic development, and slow-developing embryos activate genes related to cellular survival and/or death.

Open surgery for developmental dysplasia of the hip (DDH) may cause severe pain due to tenotomies and pelvic–femoral osteotomies. This study aims to evaluate the analgesic effect of ultrasound-guided Lumbar Erector Spina Plane (L-ESP) Block in pediatric patients undergoing DDH surgery. Sixty children scheduled for DDH surgery were randomly assigned into two groups. Group I ( n  = 30) received L-ESP with 0.5 mL/kg of 0.25% bupivacaine before surgery. In contrast, Group II ( n  = 30), as the control group, received the same volume of saline injection. Identical postoperative analgesia protocol was adjusted for both groups. Parental satisfaction, pain levels, ibuprofen, and opioid consumption were recorded. Pain levels were evaluated with the FLACC (Face, Legs, Activity, Crying, Consolability) scale. FLACC scores at the first 24th hours were lower in the L-ESP group than the control group ( p  < 0.001). Rescue opioid utilization was higher in the control group (15/26) than in the L-ESP group (2/29) ( p  < 0.001). The consumption of ibuprofen was higher in the control group than in the L-ESP group in the ward (24/26 vs. 3/29, p  < 0.001, respectively). Parental satisfaction was superior in the L-ESP group ( p  = 0.024). To provide postoperative analgesia for DDH surgery, ultrasound-guided L-ESP may be an effective and alternative regional anesthetic technique.

Background Surgical intervention is critical in the treatment of hip developmental dysplasia in children. Perioperative analgesia, usually based on high opioid dosages, is frequently used in these patients. In some circumstances, regional anesthetic procedures such as caudal block and lumbar plexus block have also been used. Previous research has shown that pericapsular nerve group (PENG) block provides excellent anesthetic efficacy during open hip surgery in adults. PENG block is thought to provide a similar analgesia effect comparable to caudal block. Methods This study is a single-center, prospective, randomized, double-blinded, non-inferiority experiment that enrolled children aged 6 months to 7 years who were scheduled for developmental dysplasia hip surgery. Following general anesthesia and regional blocks (0.25% ropivacaine at a dose of 2.5 mg·kg −1 with epinephrine at a concentration of 1:200,000), 48 individuals will be randomly assigned to either the PENG or caudal groups. The primary outcome measure is the highest FLACC (face, legs, activity, crying, consolability) score achieved within 24 h of surgery. Secondary outcomes include intraoperative opioid consumption, analgesic dosage within 24 h of surgery, time to start rescue analgesia, number of PCA pump activations, time to remove SLIPA (streamlined liner of the pharynx airway), duration of regional block procedures, incidence of adverse events, plasma ropivacaine concentrations, and hospital stays and costs. All data will be collected by blinded investigators. The trial’s final results will be published in a peer-reviewed scientific journal. Discussion We expect this trial to provide some evidences that PENG block is safe and effective for perioperative analgesia in pediatric patients undergoing open hip surgery. Trial registration Chinese Clinical Trial Registry ChiCTR2100053128. Registered on November 12, 2021.

Visuo-spatial skills are believed to be enhanced in autism spectrum disorders (ASDs). This meta-analysis tests the current state of evidence for Figure Disembedding, Block Design, Mental Rotation and Navon tasks in ASD and neurotypicals. Block Design ( d  = 0.32) and Figure Disembedding ( d  = 0.26) showed superior performance for ASD with large heterogeneity that is unaccounted for. No clear differences were found for Mental Rotation. ASD samples showed a stronger local processing preference for Navon tasks ( d  = 0.35); less clear evidence for performance differences of a similar magnitude emerged. We discuss the meta-analysis results together with other findings relating to visuo-spatial processing and three cognitive theories of ASD: Weak Central Coherence, Enhanced Perceptual Functioning and Extreme Male Brain theory.

Background Effective postoperative analgesia for pediatric developmental dysplasia of the hip (DDH) surgery remains a challenge. This study aimed to compare the analgesic efficacy of a combined fascia iliaca compartment block (FICB) and quadratus lumborum block (QLB) versus patient-controlled intravenous analgesia (PCIA) in pediatric patients undergoing open reduction surgery for DDH under general anesthesia. Methods This retrospective cohort study enrolled children under 16 years old undergoing DDH surgery between January 2016 and January 2024. Patients were divided into two groups based on the analgesia received: a Block group (FICB + QLB, n  = 35) and a PCIA group ( n  = 35). The primary outcome was postoperative pain assessed by the FLACC score at 1 and 24 h. Secondary outcomes included 24-hour opioid (fentanyl) consumption, frequency of rescue non-steroidal anti-inflammatory drug (NSAID) use, and parental satisfaction. Results The study included 35 patients in the PCIA group and 35 in the block group. FLACC pain scores were significantly lower in the Block group at both 1 h (median: 3 vs. 7, p  < 0.001) and 24 h postoperatively (median: 2 vs. 5, p  < 0.001). Total opioid consumption was markedly lower in the Block group (mean: 5.97 vs. 20.66 µg/kg, p  < 0.001), as was the need for rescue NSAIDs (median administrations: 2 vs. 4, p  < 0.001). Parental satisfaction was significantly higher in the Block group ( p  < 0.001). Conclusion The combination of FICB and QLB provides superior postoperative analgesia compared to PCIA alone in children undergoing DDH surgery, significantly reducing pain scores, opioid requirements, and rescue analgesic need, while leading to higher parental satisfaction. Clinical trial number Not applicable.

TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood. We tested the requirements for Tbx3 in these processes. We generated a unique series of Tbx3 hypomorphic and conditional mouse mutants with varying levels and locations of Tbx3 activity within the heart, and developed techniques for evaluating in vivo embryonic conduction system function. Disruption of Tbx3 function in different regions of the developing heart causes discrete phenotypes and lethal arrhythmias: sinus pauses and bradycardia indicate sinoatrial node dysfunction, whereas preexcitation and atrioventricular block reveal abnormalities in the atrioventricular junction. Surviving Tbx3 mutants are at increased risk for sudden death. Arrhythmias induced by knockdown of Tbx3 in adults reveal its requirement for conduction system homeostasis. Arrhythmias in Tbx3 -deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers. These findings indicate that Tbx3 is required for the conduction system to establish and maintain its correct molecular identity and functional properties. In conclusion, Tbx3 is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner. TBX3 and its regulatory targets merit investigation as candidates for human arrhythmias.

The paravertebral spread that occurs after erector spinae plane block may be volume-dependent. This cadaveric study was undertaken to compare the extent of paravertebral spread with erector spinae plane block using different dye volumes. After randomization, twelve erector spinae plane blocks were performed bilaterally with either 10 ml or 30 ml of dye at the level of T5 in seven unembalmed cadavers except for two cases of unexpected pleural puncture using the 10 ml injection. Direct visualization of the paravertebral space by endoscopy was performed immediately after the injections. The back regions were also dissected, and dye spread and nerve involvement were investigated. A total of five 10 ml injections and seven 30 ml injections were completed for both endoscopic and anatomical evaluations. No paravertebral spread was observed by endoscopy after any of the 10-ml injections. Dye spread to spinal nerves at the intervertebral foramen was identified by endoscopy at adjacent levels of T5 (median: three levels) in all 30 ml injections. In contrast, the cases with two, four, and three out of five were stained at only the T4, T5, and T6 levels, respectively, with the 10 ml injection. Upon anatomical dissection, all blocks were consistently associated with posterior and lateral spread to back muscles and fascial layers, especially with the 30 ml injections, which showed greater dye expansion. In one 30 ml injection, sympathetic nerve involvement and epidural spread were observed at the level of the injection site. Although paravertebral spread following erector spinae plane block increased in a volume-dependent manner, this increase was variable and not pronounced. As the injectate volume increased for the erector spinae blocks, the injectate spread to the back muscles and fascial layers seemed to be predominantly increased compared with, the extent of paravertebral spread.