Comparative efficacies of various corticosteroids for preventing postextubation stridor and reintubation: a systematic review and network meta-analysis.

Objectives: We assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation. Methods: We searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation. Results: The 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22-0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11-0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08-0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24-1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13-0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25-0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results. Conclusions: Methylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.

Laccase-Induced Gelation of Sugar Beet Pectin-Curcumin Nanocomplexes Enhanced by Genipin Crosslinking.

Research on the use of polysaccharides as hydrophobic bioactive carriers instead of proteins is still scarce. Sugar beet pectin (SBP) contains a small amount of protein and is a potential carrier for loading curcumin. In this work, SBP encapsulation, genipin crosslinking, and laccase-induced gelation were used to develop novel jelly food and improve the stability of curcumin without the incorporation of oil. By mixing the SBP solution (40 mg/mL) with curcumin powder (25 mg/mL SBP solution), an SBP-curcumin complex (SBP-Cur) was fabricated with a loading amount of 32 mg/g SBP, and the solubility of curcumin improved 116,000-fold. Fluorescence spectroscopy revealed that hydrophobic interactions drove the complexation of curcumin and SBP. Crosslinked by genipin (10 mM), SBP-Cur showed a dark blue color, and the gel strength of laccase-catalyzed gels was enhanced. Heating and UV radiation tests suggested that the genipin crosslinking and gelation strategies substantially improved the stability of curcumin. Because of the unique UV-blocking capacity of blue pigment, crosslinked samples retained 20% more curcumin than control samples. With the enhanced stability of curcumin, the crosslinked SBP-curcumin complexes could be a functional food ingredient used in functional drinks, baked food, and jelly food.

Pulsed electric field improves the EGCG binding ability of pea protein isolate unraveled by multi-spectroscopy and computer simulation.

Understanding molecular mechanisms during protein modification is critical for expanding the application of plant proteins. This study investigated the conformational change and molecular mechanism of pea protein isolate (PPI) under pulsed electric field (PEF)-assisted (-)-Epigallocatechin-Gallate (EGCG) modification. The flexibility of PPI was significantly enhanced after PEF treatment (10 kV/cm) with decrease (23.25 %) in α-helix and increase (117.25 %) in random coil. The binding constant and sites of PEF-treated PPI with EGCG were increased by 2.35 times and 10.00 % (308 K), respectively. Molecular docking verified that PEF-treated PPI had more binding sites with EGCG (from 4 to 10). The number of amino acid residues involved in hydrophobic interactions in PEF-treated PPI-EGCG increased from 5 to 13. PEF-treated PPI-EGCG showed a significantly increased antioxidant activity compared to non-PEF-treated group. This work revealed the molecular level of PEF-assisted EGCG modification of PPI, which will be significant for the application of PPI in food industry.

Mechanical Properties of Titanium/Nano-Fluorapatite Parts Produced by Laser Powder Bed Fusion.

Laser powder bed fusion (L-PBF) has attracted great interest in recent years due to its ability to produce intricate parts beyond the capabilities of traditional manufacturing processes. L-PBF processed biomedical implants are usually made of commercial pure titanium (CP-Ti) or its alloys. However, both alloys are naturally bio-inert, and thus reduce the formation of apatite as implants are put into the human body. Accordingly, in an attempt to improve the bioactivity of the materials used for making orthopedic implants, the present study decomposed fluorapatite material (FA, (Ca10(PO4)6F2)) into the form of nano-powder and mixed this powder with CP-Ti powder in two different ratios (99%Ti + 1%FA (Ti-1%FA) and 98%Ti + 2%FA (Ti-2%FA)) to form powder material for the L-PBF process. Experimental trials were conducted to establish the optimal processing conditions (i.e., laser power, scanning speed and hatching space) of the L-PBF process for the two powder mixtures and the original CP-Ti powder with no FA addition. The optimal parameters were then used to produce tensile test specimens in order to evaluate the mechanical properties of the different samples. The hardness of the various samples was also examined by micro-Vickers hardness tests. The tensile strength of the Ti-1%FA sample (850 MPa) was found to be far higher than that of the CP-Ti sample (513 MPa). Furthermore, the yield strength of the Ti-1%FA sample (785 MPa) was also much higher than that of the CP-Ti sample (472 MPa). However, the elongation of the Ti-1%FA sample (6.27 %) was significantly lower than that of the CP-Ti sample (16.17%). Finally, the hardness values of the Ti-1%FA and Ti-2%FA samples were around 63.8% and 109.4%, respectively, higher than that of the CP-Ti sample.

Structural, antioxidant, and immunomodulatory activities of an acidic exopolysaccharide from Lactiplantibacillus plantarum DMDL 9010.

This study investigated the structural, antioxidant, and immunomodulatory activities of acidic exopolysaccharide (EPS-LP2) isolated from Lactiplantibacillus plantarum DMDL 9010. EPS-LP2 is composed of fucose (Fuc), arabinose (Ara), galactose (Gal), glucose (Glc), mannose (Man), and D-fructose (Fru) with a molar ratio of 0.13: 0.69: 8.32: 27.57: 62.07: 0.58: 0.46, respectively. Structural analysis of EPS-LP2 exhibited a smooth irregular lamellar surface, rod-like structure with swollen ends and slippery surfaces, and good thermal stability. Based on the methylation and NMR analysis, sugar residues including t-Manp, t-Glcp, 2-Manp, 6-Galp, 6-Glcp, and 4-Glcp were found to exist in EPS-LP2. In the 50∼400 µg/ml range, EPS-LP2 showed negligible neurotoxicity to RAW264.7 cells. Moreover, EPS-LP2 could protect RAW264.7 cells from oxidative injury by lowering the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and the secretion of lactate dehydrogenase (LDH). In contrast, an increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and the concentrations of glutathione (GSH) were observed. Immunoreactivity assays showed that EPS-LP2 could suppress the expression of NO, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) and inhibit the activation of the mitogen-activated protein kinase (MAPK)/nuclear factor-κB-gene binding (NF-κB) cell pathway. Conclusively, EPS-LP2 could be a potential natural antioxidant and immunomodulatory agent in functional foods and medicines.

Bifunctional Monolayer WSe2/Graphene Self-Stitching Heterojunction Microreactors for Efficient Overall Water Splitting in Neutral Medium.

Developing efficient bifunctional electrocatalysts in neutral media to avoid the deterioration of electrodes or catalysts under harsh environments has become the ultimate goal in electrochemical water splitting. This work demonstrates the fabrication of an on-chip bifunctional two-dimensional (2D) monolayer (ML) WSe2/graphene heterojunction microreactor for efficient overall water splitting in a neutral medium (pH = 7). Through the synergistic atomic growth of the metallic Cr dopant and graphene stitching contact on the 2D ML WSe2, the bifunctional WSe2/graphene heterojunction microreactor consisting of a full-cell configuration demonstrates excellent performance for overall water splitting in a neutral medium. Atomic doping of metallic Cr atoms onto the 2D ML WSe2 effectively facilitates the charge transfer at the solid-liquid interface. In addition, the direct growth of the self-stitching graphene contact with the 2D WSe2 catalyst largely reduces the contact resistance of the microreactor and further improves the overall water splitting efficiency. A significant reduction of the overpotential of nearly 1000 mV at 10 mA cm-2 at the Cr-doped WSe2/graphene heterojunction microreactor compared to the ML pristine WSe2 counterpart is achieved. The bifunctional WSe2/graphene self-stitching heterojunction microreactor is an ideal platform to investigate the fundamental mechanism of emerging bifunctional 2D catalysts for overall water splitting in a neutral medium.

Succinylated whey protein isolate-chitosan core-shell composite particles as a novel carrier: Self-assembly mechanism and stability studies.

Single protein [whey protein isolate (WPI) or succinylated whey protein isolate (SWPI)] and composite particles of proteins with chitosan (CS) were tested for their ability to encapsulate and protect curcumin (CUR). Combining protein and CS resulted in changes in zeta-potential and surface hydrophobicity, particularly in the SWPI-H (high degree of succinylation, 90 %) and CS composite particle (H-CS). Furthermore, the secondary and tertiary structures were dramatically altered using Fourier transform infrared (FTIR), circular dichroism (CD), and X-ray diffraction (XRD). Scanning electron microscopy (SEM) and atomic force microscope (AFM) analyses revealed that H-CS exhibited a soft core-rigid shell morphology due to electrostatic interactions, hydrophobic interactions, and H-bond interactions. Fluorescence quenching results demonstrated that H-CS had a higher binding constant (K, 1.69 ×104 M-1) and encapsulation effectiveness (EE, 88.3 %) of CUR. Because of increased binding sites and steric hindrance, CUR was stabilized more effectively in H-CS in photostability and thermostability tests,. These results show that SWPI-CS composite particles can be utilized to build a protection system for water-insoluble nutritional supplements.

A novel 2-phase residual U-net algorithm combined with optimal mass transportation for 3D brain tumor detection and segmentation.

Utilizing the optimal mass transportation (OMT) technique to convert an irregular 3D brain image into a cube, a required input format for a U-net algorithm, is a brand new idea for medical imaging research. We develop a cubic volume-measure-preserving OMT (V-OMT) model for the implementation of this conversion. The contrast-enhanced histogram equalization grayscale of fluid-attenuated inversion recovery (FLAIR) in a brain image creates the corresponding density function. We then propose an effective two-phase residual U-net algorithm combined with the V-OMT algorithm for training and validation. First, we use the residual U-net and V-OMT algorithms to precisely predict the whole tumor (WT) region. Second, we expand this predicted WT region with dilation and create a smooth function by convolving the step-like function associated with the WT region in the brain image with a [Formula: see text] blur tensor. Then, a new V-OMT algorithm with mesh refinement is constructed to allow the residual U-net algorithm to effectively train Net1-Net3 models. Finally, we propose ensemble voting postprocessing to validate the final labels of brain images. We randomly chose 1000 and 251 brain samples from the Brain Tumor Segmentation (BraTS) 2021 training dataset, which contains 1251 samples, for training and validation, respectively. The Dice scores of the WT, tumor core (TC) and enhanced tumor (ET) regions for validation computed by Net1-Net3 were 0.93705, 0.90617 and 0.87470, respectively. A significant improvement in brain tumor detection and segmentation with higher accuracy is achieved.

Binding affinity of curcumin to bovine serum albumin enhanced by pulsed electric field pretreatment.

The present study investigated the effect of pulsed electric field (PEF) pretreatment on the interaction between bovine serum albumin (BSA) and curcumin. Fluorescence quenching results showed that proper PEF pretreatment significantly increased the binding affinity of curcumin and BSA, the binding constant increased by 6.77 times under the conditions of 15 kV/cm for 0.51 ms. However, at higher PEF strength (≥25 kV/cm) and longer processing time (≥0.68 ms), the binding affinity was weakened. PEF pretreatment made the protein structure more disordered and induced partial unfolding of BSA, exposing more hydrophobic regions, thereby increasing the binding affinity to curcumin. PEF-treated BSA (PBSA) possessed better encapsulation efficiency (95.19%) and loading capacity (5.25 mg/g) for curcumin, and the storage stability of curcumin were enhanced by the formation of a complex with PBSA. This study provides new insights into the design of BSA-based delivery systems for curcumin and other hydrophobic nutrients.

The interaction between bovine serum albumin and [6]-,[8]- and [10]-gingerol: An effective strategy to improve the solubility and stability of gingerol.

In this study, the binding mechanism between bovine serum albumin (BSA) and three gingerols ([6]-, [8]- and [10]-gingerol) was evaluated to explore an effective strategy for improving solubility and stability of gingerols. The fluorescence analysis suggested gingerols could bind with BSA to form a stable BSA/gingerols complex and [10]-gingerol had the strongest binding affinity (Ka = 4.016 × 104 L/mol) at 298 K. Thermodynamic parameters and molecular modeling validated that hydrophobic interaction and hydrogen bonds were the main driving force for the interaction of BSA/gingerols. Gingerols bound to BSA at site I (subdomain IIA) resulted in a conformational change of BSA with a structure shrinkage, which was responsible for the decrease of surface hydrophobicity. The formation of BSA/gingerols complexes promoted the solubility of [6]-, [8]- and [10]-gingerol increasing by 1.50, 6.04 and 23.50 times, respectively. In addition, the stability and antioxidant capacity of gingerols was significantly improved after binding with BSA.

Epidemiologic Study of Enterobius vermicularis Infection among Schoolchildren in the Republic of Marshall Islands.

The prevalence and risk factors of Enterobius vermicularis (pinworm) infection among primary schoolchildren (PSC) in the Marshall Islands remain unknown; thus, investigation on the status of pinworm infection rate is necessary to establish baseline data. After parents'/guardians' consent, a total of 346 children (179 boys and 167 girls) participated in this study. Individual's perianal area and thumbs were inspected by using the Scotch tape technique and cellophane tape method, respectively. For each child, demographic and risk factor data were collected by a structured questionnaire and statistically analyzed. The overall prevalence of pinworm infection was 12.14% (42/346). Univariate analysis indicated significant differences in PSC who live in an urban area compared to those who live in the rural area (p=0.01). Multivariate analysis still found that PSC who live in the rural area had higher chances to acquire pinworm infection. However, no risk factors were identified to be associated with personal hygiene, sibling number, and parent's educational level or occupation. Nevertheless, a pinworm-like egg was detected on the thumb of one male participant. Children living in the rural area and thumb-sucking behavior are two of the important risk factors of transmitting pinworm infection in the PSC in the Marshall Islands. We suggested an urgent and continuous provision of adequate hygienic sensitization in the school and the community.

Robust W/O/W Emulsion Stabilized by Genipin-Cross-Linked Sugar Beet Pectin-Bovine Serum Albumin Nanoparticles: Co-encapsulation of Betanin and Curcumin.

Betanin and curcumin hold promise as natural colorants and antioxidants for food purposes due to their anti-hypertensive, anti-inflammation, and anti-tumor effects. However, the thermal stability and bioavailability of betanin and curcumin still need improvement. Here, we fabricated sugar beet pectin-bovine serum albumin nanoparticles (SBNPs) with a mean particle size of 180 ± 5.2 nm through a genipin cross-linking strategy to stabilize a type of Pickering water-in-oil-in-water (W/O/W) emulsion and co-encapsulated betanin and curcumin. First, the W1/O emulsion was homogenized with gelatin (the gelling agent) in the water phase and polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase. Later, W1/O was homogenized with another water phase containing SBNPs. The microstructure of the emulsion was regulated by the particle concentration (c) and W1/O volume fraction (Φ), especially the gel-like high internal phase emulsions were formed at the Φ up to 70%. In this case, betanin was encapsulated in the internal water phase (encapsulation efficiency = 65.3%), whereas curcumin was in the medium-chain triglyceride (encapsulation efficiency = 84.1%). Meanwhile, the shelf stability of betanin and curcumin was improved. Furthermore, the stability of bioactive compounds was potentiated by an emulsion gel in simulated gastrointestinal digestion, resulting in higher bioaccessibility. The aforementioned results suggest that SBNP-stabilized Pickering W/O/W emulsions could be a potential alternative to co-encapsulate betanin and curcumin with enhancement of shelf stability and bioaccessibility.

Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.

Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.

Attenuation of Heat-Induced Hypothalamic Ischemia, Inflammation, and Damage by Hyperbaric Oxygen in Rats.

The present study was attempted to assess the mechanisms underlying the beneficial effects of hyperbaric oxygen (HBO2; 100% O2 at 253 kpa) in treating experimental heatstroke. Anesthetized rats were divided into five major groups: normothermic control (NC) rats treated with normobaric air (NBA; 21% O2 at 101 kpa; NC + NBA); NC rats treated with HBO2 (NC + HBO2); heatstroke (HS) rats treated with NBA (HS + NBA); HS rats treated with hyperbaric air (HBA; 21% at 253 kpa; HS + HBA); and HS rats treated with HBO2 (HS + HBO2). HS groups were exposed to heat (43°C) for exactly 68 min and then allowed to recover at 26°C. HBA or HBO2 was adopted 68 or 78 min after the start of heat exposure. Survival time values for (HS + NBA) rats, (HS + HBA) rats at 68 min, (HS + HBA) rats at 78 min, (HS + HBO2) rats at 68 min, and (HS + HBO2) rats at 78 min were found to be 90 ± 3, 133 ± 12, 109 ± 9, 240 ± 18, and 170 ± 15 min, respectively. Resuscitation with HBA or HBO2 at 68 min was superior to those treated at 78 min in prolonging the survival time values. All (HS + NBA) animals displayed hyperthermia, hypotension, and increased cellular levels of ischemia, oxidative stress and damage markers, pro-inflammatory cytokines, and an indicator of polymorphonuclear cell accumulation in their hypothalamus as compared to those of NCs. Heat-induced hyperthermia was not affected by HBA or HBO2 treatment. However, heat-induced hypotension and hypothalamic ischemia, oxidative stress, neuronal damage, and inflammation were all significantly reduced by HBA or HBO2 therapy. Compared to those of HBA therapy, HBO2 therapy had a significantly higher beneficial effect in treating heatstroke. Our results suggested that HBO2 improved heatstroke outcomes, in part, by restoring normal hypothalamic function. Delaying the onset of HBO2 therapy reduced the therapeutic efficiency.

Association between nutritional status and indicators of physical fitness and physical capacity among primary and secondary school students in Xiamen / 中国学校卫生

Objective@#To investigate the nutritional status and its relationship with the indexes of physical function and physical capacity among primary and middle school students in Xiamen, so as to provide statistical support for improving their nutritional status and physical health.@*Methods@#A total of 2 752 primary and middle school students aged between 6 and 18 years old were selected in Xiamen. They were divided into malnutrition group, normal group and overweight and obesity group according to the national standards. Statistical analysis was carried out by chi square test, Kruskal wallis test and partial correlation analysis.@*Results@#The prevalence of malnutrition among primary and secondary school students in Xiamen was 8.4%(231), the prevalence of overweight and obesity was 24.2%(667), and the prevalence of overweight and obesity among boys(31.4%) was higher than girls( 17.0 %).The distribution of nutritional status between different ages was statistically significant ( χ 2=40.43, P <0.05). On the lung activity index, both boys and girls were shown to be overweight and obesity<normal weight group<malnutrition group( χ 2=14.2,5.6; 17.2, 11.6, P <0.01)；Both girl and boy students in grip body mass index, 50 meter running and PFI were shown to be better than overweight obesity ( χ 2=99.5, 6.6, 10.4; 8.18, 5.16 , 7.13, P <0.05).@*Conclusion@#The prevention and control situation of overweight between primary and secondary school students in Xiamen city, is more serious. Overweight and obesity are related to decline in physical function and physical fitness. Nutritional status should be paid more attention for physical fitness improvement among students.

Preheated (Heat-Assisted) Clinching Process for Al/CFRP Cross-Tension Specimens.

Effects of processing parameters on preheated (heat-assisted) clinching process to join aluminum alloy 5052-H32 (AA5052) and thermoplastic carbon-fiber-reinforced-plastic (TP-CFRP) sheets for cross-tension (CT) specimens were first studied. Preheating was critical since brittle TP-CFRP could be softened to avoid fracturing or cracking during clinching process. Four processing parameters, including punching force, die depth, heating mode, and heating temperature, were considered. Quasi-static tests and microscope observations were taken to evaluate AA5052/TP-CFRP clinch joints in CT specimens and determine appropriate processing parameters for fatigue tests. Finally, fatigue data and failure mode of clinch joints in CT specimens were obtained and discussed.

Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness.

Background: Glioblastoma (GB) is one of the most common (~30%) and lethal cancers of the central nervous system. Although new therapies are emerging, chemoresistance to treatment is one of the major challenges in cancer treatment. Brain cytoplasmic 200 (BC200) RNA, also known as BCYRN1, is a long noncoding RNA (lncRNA) that has recently emerged as one of the crucial members of the lncRNA family. BC200 atypical expression is observed in many human cancers. BC200 expression is higher in invasive cancers than in benign tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods: BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine miRNAs associated with BC200 RNA. Results: Our findings revealed that in GB patients, BC200 RNA expression was higher in blood and tumor tissues than in normal tissues. BC200 RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200 RNA expression was higher than both p53, a prognostic marker of glioma, and Ki-67, a reliable indicator of tumor cell proliferation activity. Overexpression and silencing of BC200 RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions: This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical biomarker or therapeutic target for GB.

E2A-PBX1 functions as a coactivator for RUNX1 in acute lymphoblastic leukemia.

E2A, a basic helix-loop-helix transcription factor, plays a crucial role in determining tissue-specific cell fate, including differentiation of B-cell lineages. In 5% of childhood acute lymphoblastic leukemia (ALL), the t(1,19) chromosomal translocation specifically targets the E2A gene and produces an oncogenic E2A-PBX1 fusion protein. Although previous studies have shown the oncogenic functions of E2A-PBX1 in cell and animal models, the E2A-PBX1-enforced cistrome, the E2A-PBX1 interactome, and related mechanisms underlying leukemogenesis remain unclear. Here, by unbiased genomic profiling approaches, we identify the direct target sites of E2A-PBX1 in t(1,19)-positive pre-B ALL cells and show that, compared with normal E2A, E2A-PBX1 preferentially binds to a subset of gene loci cobound by RUNX1 and gene-activating machineries (p300, MED1, and H3K27 acetylation). Using biochemical analyses, we further document a direct interaction of E2A-PBX1, through a region spanning the PBX1 homeodomain, with RUNX1. Our results also show that E2A-PBX1 binding to gene enhancers is dependent on the RUNX1 interaction but not the DNA-binding activity harbored within the PBX1 homeodomain of E2A-PBX1. Transcriptome analyses and cell transformation assays further establish a significant RUNX1 requirement for E2A-PBX1-mediated target gene activation and leukemogenesis. Notably, the RUNX1 locus itself is also directly activated by E2A-PBX1, indicating a multilayered interplay between E2A-PBX1 and RUNX1. Collectively, our study provides the first unbiased profiling of the E2A-PBX1 cistrome in pre-B ALL cells and reveals a previously unappreciated pathway in which E2A-PBX1 acts in concert with RUNX1 to enforce transcriptome alterations for the development of pre-B ALL.

Enterobius vermicularis infection: prevalence and risk factors among preschool children in kindergarten in the capital area, Republic of the Marshall Islands.

BACKGROUND: Enterobius vermicularis (pinworm) is one of the most common human parasitic helminths, and children are the most susceptible group. Some behavioral and environmental factors may facilitate pinworm infection. In the Republic of the Marshall Islands (RMI), the status of pinworm infections among children remains unknown. METHODS: In Majuro City, there are 14 kindergartens with a total of 635 preschool children (PSC) whose age range of 5~6 years. The present investigation attempted to determine the pinworm prevalence and associated risk factors as well as investigate whether eggs contaminated the clothes of PSC or the ground and tables in classrooms of 14 kindergartens. Informed consent form and a self-administered questionnaire were given to parents prior to pinworm screening. Perianal specimens were collected by an adhesive scotch tape method, and clothing of belly and hip sites and the ground and tables of the classrooms were inspected using a cellophane tape method to detect any eggs contamination. RESULTS: In total, 392 PSC (5.28 ± 0.56 yrs. old) participated in this project. The overall prevalence of pinworm infection was 22.4% (88/392). Boys (24.5%) had higher prevalence than girls (20.31%) (p = 0.32). PSC aged > 5 years (32.77%) showed a significantly higher prevalence than those aged ≤5 years (17.95%) (p = 0.01). A univariate analysis indicated that PSC who lived in urban areas (22.95%) had a higher prevalence than those who lived in rural areas (20.69%) (p = 0.69). The employment status of the parents showed no association with the pinworm infection rate (p > 0.05). A logistic regression analysis indicated that "having an older sister" produced a higher risk of acquiring pinworm infection for PSC compared to those who did not have an older sister (OR = 2.02; 95%CI = 1.05~3.88; p = 0.04). No significant association between various other risk factors and pinworm infection was found (p > 0.05). Also, no eggs contamination was found on the clothes of the belly and hip sites or on the ground and tables in the 14 kindergartens. CONCLUSIONS: Mass screening and treatment of infected PSC are important measures in pinworm control in the RMI.