The crescent-like Golgi ribbon is shaped by the Ajuba/PRMT5/Aurora-A complex-modified HURP.

BACKGROUND: Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon. METHODS: To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon. RESULTS: The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery. CONCLUSIONS: The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape. Video Abstract.

The PRMT5/HURP axis retards Golgi repositioning by stabilizing acetyl-tubulin and Golgi apparatus during cell migration.

The Golgi apparatus (GA) translocates to the cell leading end during directional migration, thereby determining cell polarity and transporting essential factors to the migration apparatus. The study provides mechanistic insights into how GA repositioning (GR) is regulated. We show that the methyltransferase PRMT5 methylates the microtubule regulator HURP at R122. The HURP methylation mimicking mutant 122F impairs GR and cell migration. Mechanistic studies revealed that HURP 122F or endogenous methylated HURP, that is, HURP m122, interacts with acetyl-tubulin. Overexpression of HURP 122F stabilizes the bundling pattern of acetyl-tubulin by decreasing the sensitivity of the latter to a microtubule disrupting agent nocodazole. HURP 122F also rigidifies GA via desensitizing the organelle to several GA disrupting chemicals. Similarly, the acetyl-tubulin mimicking mutant 40Q or tubulin acetyltransferase αTAT1 can rigidify GA, impair GR, and retard cell migration. Reversal of HURP 122F-induced GA rigidification, by knocking down GA assembly factors such as GRASP65 or GM130, attenuates 122F-triggered GR and cell migration. Remarkably, PRMT5 is found downregulated and the level of HURP m122 is decreased during the early hours of wound healing-based cell migration, collectively implying that the PRMT5-HURP-acetyl-tubulin axis plays the role of brake, preventing GR and cell migration before cells reach empty space.

The JMJD6/HURP axis promotes cell migration via NF-κB-dependent centrosome repositioning and Cdc42-mediated Golgi repositioning.

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA-associated acetyl-tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6-guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6-induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF-κB-induced CR and subsequently CR-dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF-κB-CR-Cdc42 cascade collectively dictate GR.

Association Between Insurance and the Transfer of Children With Mental Health Emergencies.

OBJECTIVES: This study sought to investigate the association between a patient's insurance coverage and a hospital's decision to admit or transfer pediatric patients presenting to the emergency department (ED) with a mental health disorder. METHODS: This is a cross-sectional study of pediatric mental health ED admission and transfer events using the Healthcare Cost and Utilization Project 2014 Nationwide Emergency Department Sample. Children presenting to an ED with a primary mental health disorder who were either admitted locally or transferred to another hospital were included. Multivariable logistic regression models were used to adjust for confounders. RESULTS: Nineteem thousand eighty-one acute mental health ED events among children were included in the analyses. The odds of transfer relative to admission were higher for children without insurance (odds ratio, 3.30; 95% confidence interval, 1.73-6.31) compared with patients with private insurance. The odds of transfer were similar for children with Medicaid compared with children with private insurance (odds ratio, 1.23; 95% confidence interval, 0.80-1.88). Transfer rates also varied across mental health diagnostic categories. Patients without insurance had higher odds of transfer compared with those with private insurance when they presented with depressive disorder, bipolar disorder, attention-deficit/conduct disorders, and schizophrenia. CONCLUSIONS: Children presenting to an ED with a mental health emergency who do not have insurance are more likely to be transferred to another hospital than to be admitted and treated locally compared with those with private insurance. Future studies are needed to determine factors that may protect patients without insurance from disparities in access to care.

Overexpression of Aurora-A bypasses cytokinesis through phosphorylation of suppressed in lung cancer.

Mitosis is a complicated process by which eukaryotic cells segregate duplicated genomes into two daughter cells. To achieve the goal, numerous regulators have been revealed to control mitosis. The oncogenic Aurora-A is a versatile kinase responsible for the regulation of mitosis including chromosome condensation, spindle assembly, and centrosome maturation through phosphorylating a range of substrates. However, overexpression of Aurora-A bypasses cytokinesis, thereby generating multiple nuclei by unknown the mechanisms. To explore the underlying mechanisms, we found that SLAN, a potential tumor suppressor, served as a substrate of Aurora-A and knockdown of SLAN induced immature cytokinesis. Aurora-A phosphorylates SLAN at T573 under the help of the scaffold protein 14-3-3η. The SLAN phosphorylation-mimicking mutants T573D or T573E, in contrast to the phosphorylation-deficiency mutant T573A, induced higher level of multinucleated cells, and the endogenous SLAN p573 resided at spindle midzone and midbody with the help of the microtubule motor MKLP1. The Aurora-A- or SLAN-induced multiple nuclei was prevented by the knockdown of 14-3-3η or Aurora-A respectively, thereby revealing a 14-3-3η/Aurora-A/SLAN cascade negatively controlling cytokinesis. Intriguingly, SLAN T573D or T573E inactivated and T573A activated the key cytokinesis regulator RhoA. RhoA interacted with SLAN np573, i.e., the nonphosphorylated form of SLAN at T573, which localized to the spindle midzone dictated by RhoA and ECT2. Therefore, we report here that SLAN mediates the Aurora-A-triggered cytokinesis bypass and SLAN plays dual roles in that process depending on its phosphorylation status.

The Association Between Insurance and Transfer of Noninjured Children From Emergency Departments.

STUDY OBJECTIVE: Among children requiring hospital admission or transfer, we seek to determine whether insurance is associated with the decision to either admit locally or transfer to another hospital. METHODS: This cross-sectional study used Healthcare Cost and Utilization Project 2012 Nationwide Emergency Department Sample. Pediatric patients receiving care in emergency departments (EDs) who were either admitted or transferred were included. Clinical Classifications Software was used to categorize patients into noninjury diagnostic cohorts. Multivariable logistic regression models adjusting for potential confounders, including severity of illness and comorbidities, and incorporating nationally representative weights were used to determine the association between insurance and the odds of transfer relative to admission. RESULTS: A total of 240,620 noninjury pediatric ED events met inclusion criteria. Patient and hospital characteristics, including older age and nonteaching hospitals, were associated with greater odds of transfer relative to admission. Patients who were uninsured or had self-pay had higher odds of transfer (odds ratio [OR] 3.84; 95% confidence interval [CI] 2.08 to 7.09) relative to admission compared with those with private insurance. Uninsured and self-pay patients also had higher odds of transfer across all 13 diagnostic categories, with ORs ranging from 2.96 to 12.00. Patients with Medicaid (OR 1.05; 95% CI 0.90 to 1.22) and other insurances (OR 1.14; 95% CI 0.87 to 1.48) had similar odds of transfer compared with patients with private insurance. CONCLUSION: Children without insurance and those considered as having self-pay are more likely to be transferred to another hospital than to be admitted for inpatient care within the same receiving hospital compared with children with private insurance. This study reinforces ongoing concerns about disparities in the provision of pediatric ED and inpatient care.

Enhanced interfacial activity of multi-arm poly(ethylene oxide) star polymers relative to linear poly(ethylene oxide) at fluid interfaces.

Interfacial tension reduction, dynamic dilatational elasticity and extent of adsorption were investigated for linear poly(ethylene oxide) (PEO) chains of varying molecular weight and for PEO star polymers with an average of 64 arms per star at air/water, xylene/water, and cyclohexane/water interfaces. Adsorption on planar interfaces was monitored by ellipsometry, while interfacial tension and dilatational elasticity were measured separately by pendant drop tensiometry. Previously reported to be efficient emulsifiers, PEO stars are shown here to also be more effective foaming agents than linear PEO. Accordingly, PEO stars adsorb to a greater extent and produce larger interfacial tension reduction and greater dynamic dilatational moduli than linear PEO. The more extensive adsorption and greater interfacial tension reduction for PEO stars are attributed to their compactness. More mass is introduced per unit area of interface, and more interfacial penetration is achieved, upon their adsorption than for adsorption of linear polymers that adopt the conformation of loops, trains and tails. Whereas cyclohexane is a non-solvent for PEO, xylene is a good solvent. Dispersing PEO stars in the xylene phase yields greater interfacial tension reduction at the xylene/water interface than occurs when initially dispersing PEO stars in the aqueous phase. In contrast, the interfacial tension for linear PEO shows no dependence on the phase from which it adsorbs. Ellipsometry confirms the path-dependent extent of adsorption to the xylene/water interface, but also reveals additional complexity. When adsorbing from xylene, thick interfacial films result that likely contain dispersed water, as suggested by the observation of spontaneous water-in-xylene emulsification when PEO stars are initially dispersed in xylene. This is tentatively attributed to shear provided by Marangoni flow. Spontaneous emulsification occurs only when PEO stars are initially dispersed in the xylene phase. Linear PEO produces neither thick interfacial films nor spontaneous emulsification.

Robust scaling of strength and elastic constants and universal cooperativity in disordered colloidal micropillars.

We study the uniaxial compressive behavior of disordered colloidal free-standing micropillars composed of a bidisperse mixture of 3- and 6-µm polystyrene particles. Mechanical annealing of confined pillars enables variation of the packing fraction across the phase space of colloidal glasses. The measured normalized strengths and elastic moduli of the annealed freestanding micropillars span almost three orders of magnitude despite similar plastic morphology governed by shear banding. We measure a robust correlation between ultimate strengths and elastic constants that is invariant to relative humidity, implying a critical strain of ∼0.01 that is strikingly similar to that observed in metallic glasses (MGs) [Johnson WL, Samwer K (2005) Phys Rev Lett 95:195501] and suggestive of a universal mode of cooperative plastic deformation. We estimate the characteristic strain of the underlying cooperative plastic event by considering the energy necessary to create an Eshelby-like ellipsoidal inclusion in an elastic matrix. We find that the characteristic strain is similar to that found in experiments and simulations of other disordered solids with distinct bonding and particle sizes, suggesting a universal criterion for the elastic to plastic transition in glassy materials with the capacity for finite plastic flow.

Heterogeneity in the Small-Scale Deformation Behavior of Disordered Nanoparticle Packings.

Atomic force microscopy-based nanoindentation is used to image and probe the local mechanical properties of thin disordered nanoparticle packings. The probed region is limited to the size of a few particles, and an individual particle can be loaded and displaced to a fraction of a single particle radius. The results demonstrate heterogeneous mechanical response that is location-dependent. The weak locations may be analogous to the "soft spots" previously predicted in glasses and other disordered packings.

Impact of Telemedicine on Severity of Illness and Outcomes Among Children Transferred From Referring Emergency Departments to a Children's Hospital PICU.

OBJECTIVES: To compare the severity of illness and outcomes among children admitted to a children's hospital PICU from referring emergency departments with and without access to a pediatric critical care telemedicine program. DESIGN: Retrospective cohort study. SETTING: Tertiary academic children's hospital PICU. PATIENTS: Pediatric patients admitted directly to the PICU from referring emergency departments between 2010 and 2014. INTERVENTIONS: None. MEASUREMENTS: Demographic factors, severity of illness, and clinical outcomes among children receiving care in emergency departments with and without access to pediatric telemedicine, as well as a subcohort of children admitted from emergency departments before and after the implementation of telemedicine. MAIN RESULTS: Five hundred eighty-two patients from 15 emergency departments with telemedicine and 524 patients from 60 emergency departments without telemedicine were transferred and admitted to the PICU. Children admitted from emergency departments using telemedicine were younger (5.6 vs 6.9 yr; p< 0.001) and less sick (Pediatric Risk of Mortality III score, 3.2 vs 4.0; p < 0.05) at admission to the PICU compared with children admitted from emergency departments without telemedicine. Among transfers from emergency departments that established telemedicine programs during the study period, children arrived significantly less sick (mean Pediatric Risk of Mortality III scores, 1.2 units lower; p = 0.03) after the implementation of telemedicine (n = 43) than before the implementation of telemedicine (n = 95). The observed-to-expected mortality ratios of posttelemedicine, pretelemedicine, and no-telemedicine cohorts were 0.81 (95% CI, 0.53-1.09), 1.07 (95% CI, 0.53-1.60), and 1.02 (95% CI, 0.71-1.33), respectively. CONCLUSIONS: The implementation of a telemedicine program designed to assist in the care of seriously ill children receiving care in referring emergency departments was associated with lower illness severity at admission to the PICU. This study contributes to the body of evidence that pediatric critical care telemedicine programs assist referring emergency departments in the care of critically ill children and could result in improved clinical outcomes.

Tailoring the permselectivity of water desalination membranes via nanoparticle assembly.

Thin film composite membranes can selectively separate mono- and divalent ions from water via solution-diffusion of each species through a dense but ultrathin, highly cross-linked polymer "skin" layer; water is transported across the membrane faster than associated salts. Changing the selectivity of the "skin" layer typically requires adjusting the monomer chemistries that make up the polymer "skin" layer, but doing so also impacts a host of other membrane properties. Here, we employ electrostatic layer-by-layer deposition of inorganic nanoparticles to enhance the permselectivity of an existing commercial nanofiltration membrane. We chose this approach because it is simple and robust and does not require any change to the underlying chemistry of the thin film composite (TFC) membrane. We found that a single layer of nanoparticles was sufficient to increase the permselectivity of the membrane by nearly 50%, compared to the virgin TFC membrane. In order to understand the mechanism for permselectivity enhancement, we developed a modified solution-diffusion model to account for the additional hydraulic resistance of the nanoparticle layer, which can faithfully capture the effect of nanoparticle layer thickness on the observed water and salt flux of the modified TFC membrane.

Synthesis and mechanical response of disordered colloidal micropillars.

We present a new approach for studying the uniaxial compressive behavior of colloidal micropillars as a function of the initial defect population, pillar and colloid dimension, and particle-particle interaction. Pillars composed of nanometer scale particles develop cracks during drying, while pillars composed of micron scale particles dry crack-free. We subject the free-standing pillars, with diameters of 580 µm and 900 µm, to uniaxial compression experiments using a custom-built micromechanical testing apparatus. In pillars with pre-existing cracks, compression activates the macroscopic defects, leading to fracture and stochastic mechanical response as a result of the flaw distribution. Pillars that dry crack-free fail by shear bands that initiate near the punch face. While macroscopically identical, pillar-to-pillar mechanical response varies significantly. We attribute the disparate response to varying structure and environmental conditions. To isolate the effects of environment, we performed controlled experiments over a range of relative humidity levels (<2% to >98% RH). The level of atmospheric humidity affects particle-particle cohesion and friction, resulting in dramatically different mechanical responses. We discuss the results in the context of underlying particle rearrangements leading to mesoscopic shear localization and examine comparisons with atomic disordered systems such as metallic glasses.

Reliability of a short diet and vitamin supplement questionnaire for retrospective collection of maternal nutrient intake.

Background: Gestational nutrition can protect against adverse neurodevelopmental outcomes. Objectives: We developed a short tool for collecting maternal nutritional intake during pregnancy to facilitate research in this area and compared its retrospective use to prospectively-collected food frequency questionnaires (FFQ). Methods: Maternal nutritional intake was retrospectively assessed using three versions (full interview, full self-administered online, and shortened interview) of the Early Life Exposure Assessment Tool (ELEAT) among participants of the MARBLES pregnancy cohort study of younger siblings of autistic children. Retrospective responses were compared with responses to supplement questions and the validated 2005 Block FFQ prospectively collected in MARBLES during pregnancies 2-7 years prior. ELEAT nutrient values were calculated using reported food intake frequencies and nutrient values from the USDA nutrient database. Correlations between retrospectively- and prospectively-reported intake were evaluated using Kappa coefficients, Youden's J, and Spearman Rank Correlation Coefficients (rs). Results: MARBLES FFQ dietary intakes were compared among 54 women who completed the ELEAT full form including 12 online, and among 23 who completed the ELEAT short form. Correlations across most foods were fair to moderate. Most ELEAT quantified nutrient values were moderately correlated (rs = 0.3-0.6) with those on the Block FFQ. Supplement questions in both MARBLES and the ELEAT were completed by 114 women. Kappas were moderate for whether or not supplements were taken, but modest for timing. Correlations varied by version and child diagnosis or concerns, and were higher when mothers completed the ELEAT when their child was 4 years old or younger. Conclusions: With recall up to several years, ELEAT dietary and supplement module responses were modestly to moderately reliable and produced nutrient values moderately correlated with prospectively-collected measures. The ELEAT dietary and vitamin supplements modules can be used to rank participants in terms of intake of several nutrients relevant for neurodevelopment.

Primary tumor type prediction based on US nationwide genomic profiling data in 13,522 patients.

Timely and accurate primary tumor diagnosis is critical, and misdiagnoses and delays may cause undue health and economic burden. To predict primary tumor types based on genomics data from a de-identified US nationwide clinico-genomic database (CGDB), the XGBoost-based Clinico-Genomic Machine Learning Model (XC-GeM) was developed to predict 13 primary tumor types based on data from 12,060 patients in the CGDB, derived from routine clinical comprehensive genomic profiling (CGP) testing and chart-confirmed electronic health records (EHRs). The SHapley Additive exPlanations method was used to interpret model predictions. XC-GeM reached an outstanding area under the curve (AUC) of 0.965 and Matthew's correlation coefficient (MCC) of 0.742 in the holdout validation dataset. In the independent validation cohort of 955 patients, XC-GeM reached 0.954 AUC and 0.733 MCC and made correct predictions in 77% of non-small cell lung cancer (NSCLC), 86% of colorectal cancer, and 84% of breast cancer patients. Top predictors for the overall model (e.g. tumor mutational burden (TMB), gender, and KRAS alteration), and for specific tumor types (e.g., TMB and EGFR alteration for NSCLC) were supported by published studies. XC-GeM also achieved an excellent AUC of 0.880 and positive MCC of 0.540 in 507 patients with missing primary diagnosis. XC-GeM is the first algorithm to predict primary tumor type using US nationwide data from routine CGP testing and chart-confirmed EHRs, showing promising performance. It may enhance the accuracy and efficiency of cancer diagnoses, enabling more timely treatment choices and potentially leading to better outcomes.

Multi-omics analysis reveals PUS1 triggered malignancy and correlated with immune infiltrates in NSCLC.

Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer. In this study, multi-omics analysis revealed a significant increase of pseudouridine synthase 1 (PUS1) in NSCLC and the high expression of PUS1 was associated with shorter OS (Overall Survival), PFS (Progression Free Survival), and PPS (Post Progression Survival) of NSCLC patients. Clinical subgroup analysis showed that PUS1 may be involved in the occurrence and development of NSCLC. Besides, TIMER, ESTIMATE, and IPS analysis suggested that PUS1 expression was associated with immune cell infiltration, and the expression of PUS1 was significantly negatively correlated with DC cell infiltration. GESA analysis also indicated PUS1 may involve in DNA_REPAIR, E2F_TARGETS, MYC_TARGETS_V2, G2M_CHECKPOINT and MYC_TARGETS_V1 pathways and triggered NSCLC malignancy through MCM5 or XPO1. Furthermore, PUS1 may be a potential target for NSCLC therapy.

Synergistic Effect of Thermoresponsive and Photocuring Methacrylated Chitosan-Based Hybrid Hydrogels for Medical Applications.

The thermoresponsive drug-loaded hydrogels have attracted widespread interest in the field of medical applications due to their ease of delivery to structurally complex tissue defects. However, drug-resistant infections remain a challenge, which has prompted the development of new non-antibiotic hydrogels. To this end, we prepared chitosan-methacrylate (CTSMA)/gelatin (GEL) thermoresponsive hydrogels and added natural phenolic compounds, including tannic acid, gallic acid, and pyrogallol, to improve the efficacy of hydrogels. This hybrid hydrogel imparted initial crosslinking at physiological temperature, followed by photocuring to further provide a mechanically robust structure. Rheological analysis, tensile strength, antibacterial activity against E. coli, S. aureus, P. gingivalis, and S. mutans, and L929 cytotoxicity were evaluated. The experimental results showed that the hybrid hydrogel with CTSMA/GEL ratio of 5/1 and tannic acid additive had a promising gelation temperature of about 37 °C. The presence of phenolic compounds not only significantly (p < 0.05) enhanced cell viability, but also increased the tensile strength of CTSMA/GEL hybrid hydrogels. Moreover, the hydrogel containing tannic acid revealed potent antibacterial efficacy against four microorganisms. It was concluded that the hybrid hydrogel containing tannic acid could be a potential composite material for medical applications.

Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring.

STUDY OBJECTIVES: Despite its association with severe health conditions, the etiology of sleep apnea (SA) remains understudied. This study sought to identify genetic variants robustly associated with SA risk. METHODS: We performed a genome-wide association study (GWAS) meta-analysis of SA across five cohorts (NTotal = 523 366), followed by a multi-trait analysis of GWAS (multi-trait analysis of genome-wide association summary statistics [MTAG]) to boost power, leveraging the high genetic correlation between SA and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional and joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal = 1 477 352; Ncases = 175 522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. RESULTS: Our SA meta-analysis identified five independent variants with evidence of association beyond genome-wide significance. After adjustment for BMI, only one genome-wide significant variant was identified. MTAG analyses uncovered 49 significant independent loci associated with SA risk. Twenty-nine variants were replicated in the 23andMe GWAS adjusting for BMI. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. CONCLUSION: Our study uncovered multiple genetic loci associated with SA risk, thus increasing our understanding of the etiology of this condition and its relationship with other complex traits.

[Strengths and Difficulties Questionnaire in 737 primary and middle school students aged 6 -17 in Changsha].

OBJECTIVE: To explore the mental health condition of primary and middle school students in Changsha and to provide reference for future evaluation or intervention. METHODS: Strengths and Difficulties Questionnaire (SDQ) (the edition for parents) was used to investigate 737 primary and middle school students aged 6-17 in Changsha. RESULTS: The prevalence of difficulty was 14.11%. The males showed higher scores of problem, hyperactivity and impact, while the females scored higher in emotional symptom as well as prosocial behaviors. Students aged 11-13 and 14-17 showed higher scores of total difficulties, peer problems and emotional symptom than those aged 6-10. Apart from higher scores of total difficulties and peer problems, the other scores were similar to the normal scores in China. there was significant difference in the normal scores between china and other countries. CONCLUSION: mental health problems have divergent characters in gender and age. This study also highlights the importance of establishing local norms of SDQ and the need for appropriate measures in practical situations.

Antibacterial ability and osteogenic activity of polyphenol-tailored calcium silicate bone cement.

Calcium silicate-based cement (CSC) has attracted much interest because of its favourable osteogenic effect that supports its clinical use. Although CSC has antibacterial activity, this activity still needs to be improved when used in an infected bone defect. Natural polyphenols have been considered antimicrobial reagents. To this end, three different types of polyphenols (gallic acid (GA), pyrogallol (PG) and tannic acid (TA)) with different concentrations as a liquid phase were mixed with bioactive calcium silicate to enhance the antibacterial activity of CSC. The setting time, antibacterial activity, and osteogenic activity of CSC were studied. Evaluation of antibacterial ability and reactive oxygen species (ROS) was performed using Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, while a human osteoblast-like cell line (MG63) was used to examine osteogenic activity. The experimental results showed that the addition of polyphenols did not remarkably affect the phase composition and morphology of CSC, but changed the setting time and diametral tensile strength. At the same concentration of 1 wt%, the setting time of TA (21 min) was significantly shorter than that of PG (26 min) and GA (68 min), and was indistinguishable from the control cement (20 min). GA had a significantly higher antioxidant activity than PG and TA. As expected, higher concentrations of polyphenols had a more positive impact on ROS generation. More importantly, the incorporation of polyphenols greatly enhanced the antibacterial activity of CSC against E. coli and S. aureus, but had little effect on the in vitro osteogenic activity of MG63 cells and the cytotoxicity of L929 cells. It was concluded that among the three phenolic compounds, the optimal concentration of the liquid phase in the hybrid cement was 5 wt% TA in terms of setting time, strength, antibacterial activity and in vitro osteogenic activity.

Genetic determinants of daytime napping and effects on cardiometabolic health.

Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n = 541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference.