Risk factors for recurrent wheezing after bronchiolitis.

BACKGROUND: This study aimed to determine whether there was an association between certain factors in patients with bronchiolitis and recurrent wheezing in childhood. METHOD: In 2021 we tracked children hospitalized for bronchiolitis at Chengdu Women's and Children's Central Hospital in 2017. The patients were classified into recurrent wheezing group (RWG) and non-recurrent wheezing group (NRWG). Possible risk factors including maternal age, school-age siblings, allergic history, atopic dermatitis, allergic rhinitis, atopic family history, severity of the condition, duration of hospitalization, nasopharyngeal secretions culture, blood eosinophil counts, FeNO and skin prick test were compared between the two groups. Continuous variables were analyzed by independent sample t-test for normal distribution and Mann-Whitney U-test for non-normal distribution. Categorical variables were tested using chi-square tests. Multifactor analysis was conducted by stepwise logistics regression analysis. RESULTS: In total 167 participants were included, of which 26 and 141 were in RWG and NRWG respectively. In RWG children represented higher maternal age (P = 0.02) and greater probability of allergic history, atopic dermatitis, allergic rhinitis, atopic family history (odds ratio [OR] = 4.0,3.7, 7.8, 10.9 respectively, P < 0.01). However, school-age siblings, severity of the condition, duration of hospitalization, blood eosinophil counts, fractional exhaled nitric oxide and skin prick test results seemed unrelated to recurrent wheezing. In the subgroup analysis of nasopharyngeal secretion culture, there were more Moraxella catarrhalis-positive in RWG(P = 0.043). Atopic dermatitis, allergic rhinitis and atopic family history were identified as independent risk factors for recurrent wheezing. CONCLUSION: Some children with bronchiolitis will develop recurrent wheezing, and the risk factors are allergic history, Moraxella catarrhalis infection or colonization, atopic dermatitis, allergic rhinitis and atopic family history; the latter three are independent risk factors.

Tumor suppressor p53: from engaging DNA to target gene regulation.

The p53 transcription factor confers its potent tumor suppressor functions primarily through the regulation of a large network of target genes. The recent explosion of next generation sequencing protocols has enabled the study of the p53 gene regulatory network (GRN) and underlying mechanisms at an unprecedented depth and scale, helping us to understand precisely how p53 controls gene regulation. Here, we discuss our current understanding of where and how p53 binds to DNA and chromatin, its pioneer-like role, and how this affects gene regulation. We provide an overview of the p53 GRN and the direct and indirect mechanisms through which p53 affects gene regulation. In particular, we focus on delineating the ubiquitous and cell type-specific network of regulatory elements that p53 engages; reviewing our understanding of how, where, and when p53 binds to DNA and the mechanisms through which these events regulate transcription. Finally, we discuss the evolution of the p53 GRN and how recent work has revealed remarkable differences between vertebrates, which are of particular importance to cancer researchers using mouse models.

Antifouling Polymer Brushes via Oxygen-Tolerant Surface-Initiated PET-RAFT.

This work presents a new method for the synthesis of antifouling polymer brushes using surface-initiated photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization with eosin Y and triethanolamine as catalysts. This method proceeds in an aqueous environment under atmospheric conditions without any prior degassing and without the use of heavy metal catalysts. The versatility of the method is shown by using three chemically different monomers: oligo(ethylene glycol) methacrylate, N-(2-hydroxypropyl)methacrylamide, and carboxybetaine methacrylamide. In addition, the light-triggered nature of the polymerization allows the creation of complex three-dimensional structures. The composition and topological structuring of the brushes are confirmed by X-ray photoelectron spectroscopy and atomic force microscopy. The kinetics of the polymerizations are followed by measuring the layer thickness with ellipsometry. The polymer brushes demonstrate excellent antifouling properties when exposed to single-protein solutions and complex biological matrices such as diluted bovine serum. This method thus presents a new simple approach for the manufacturing of antifouling coatings for biomedical and biotechnological applications.

Revealing a human p53 universe.

p53 transcriptional networks are well-characterized in many organisms. However, a global understanding of requirements for in vivo p53 interactions with DNA and relationships with transcription across human biological systems in response to various p53 activating situations remains limited. Using a common analysis pipeline, we analyzed 41 data sets from genome-wide ChIP-seq studies of which 16 have associated gene expression data, including our recent primary data with normal human lymphocytes. The resulting extensive analysis, accessible at p53 BAER hub via the UCSC browser, provides a robust platform to characterize p53 binding throughout the human genome including direct influence on gene expression and underlying mechanisms. We establish the impact of spacers and mismatches from consensus on p53 binding in vivo and propose that once bound, neither significantly influences the likelihood of expression. Our rigorous approach revealed a large p53 genome-wide cistrome composed of >900 genes directly targeted by p53. Importantly, we identify a core cistrome signature composed of genes appearing in over half the data sets, and we identify signatures that are treatment- or cell-specific, demonstrating new functions for p53 in cell biology. Our analysis reveals a broad homeostatic role for human p53 that is relevant to both basic and translational studies.

Diagnosis of solitary pulmonary lesions with intravoxel incoherent motion diffusion-weighted MRI and semi-quantitative dynamic contrast-enhanced MRI.

AIM: To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) diffusion-weighted (DWI) magnetic resonance imaging (MRI) and semi-quantitative dynamic contrast-enhanced MRI (DCE-MRI) to help diagnose indeterminate solitary pulmonary lesions (SPLs) and the subgroups of lung cancer (LC), and to explore the relationship between IVIM and DCE-MRI. MATERIALS AND METHODS: Sixty-four consecutive patients (44 male, 20 female; age, 52.77±10.46 years) from February 2014 to September 2016 with SPLs, were involved in this prospective study. Total apparent diffusion coefficient (ADCtotal), tissue diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (F), maximum enhancement ratio (MER), Tmax, slope, and washout were compared between the lung cancer (LC) and benign group and among the subtypes of LC. Time-intensity curves (TICs) were drawn. Receiver operating characteristic (ROC) curves were constructed to estimate the diagnostic performance. The correlation of both tools was assessed. RESULTS: ADCtotal, D, and Tmax were significantly higher for benignity than for LC (p=0.005, p=0.002 and p<0.001 respectively). D* and slope were significantly higher in LC than benignity (p=0.005 and p=0.011, respectively). D and Tmax had the highest sensitivity and accuracy, respectively. A combination of D and Tmax improved the sensitivity to 90.5%, the specificity to 86.4%, and the accuracy to 89.1%. Poor correlations were found between parameters derived from IVIM and DCE-MRI. ADCtotal values of SCC and SCLC were found to be significantly lower compared with that in adenocarcinoma. CONCLUSION: Both IVIM-DWI and DCE-MRI were useful for discriminating benignity from LC. ADCtotal was helpful for distinguishing adenocarcinoma and non-adenocarcinoma. A combination of DCE-MRI and IVIM could provide a robust method to determine the microstructural characteristics of SPLs.

[A comparative study of lacrimal magnetic resonance hydrography and lacrimal endoscopy examination in the diagnosis and treatment of lacrimal duct obstructive diseases].

OBJECTIVE: To evaluate the diagnostic value and treatment guidance of lacrimal magnetic resonance hydrography (LMRH) and lacrimal endoscopy examination in lacrimal duct obstruction. METHODS: A retrospective analysis of clinical and imaging data of 59 patients with epiphora who had LMRH examination in Tongji Hospital during June 2013 and January 2014. Multiplanar reconstruction (MPR) and maximum intensity projection (MIP) were used to process the three dimensions T2-weighted images (T2WI). The size of lacrimal sac, lacrimal mucosal lesions and the obstructed plane of nasolacrimal duct were observed. The lacrimal irrigation results were used as gold standard. The sensitivity, specificity, accuracy of LMRH in diagnosis of lacrimal duct obstructive diseases and the consistency between the two methods were analyzed. In addition, 22 cases had lacrimal endoscopy examination in less than half month after MRD. The results of lacrimal endoscopy were compared with LMRH images. The treatment method was made according to the results of LMRH and lacrimal endoscopy. RESULTS: According to the results of lacrimal irrigation, among 78 eyes of 59 patients, 2 eyes were diagnosed as lacrimal canalicular obstruction (2.6%, 2/78), 8 eyes were diagnosed as nasolacrimal duct stenosis (10.3%, 8/78), 24 eyes were diagnosed as nasolacrimal duct obstruction (30.8%, 24/78), 44 eyes were diagnosed as nasolacrimal duct obstruction accompanied with chronic dacryocystitis (56.4%, 44/78). The other 40 eyes were negative controls. LMRH had a high degree of consistency with lacrimal irrigation in diagnosis of lacrimal duct obstructive diseases. The value of Kappa was 0.963 (P= 0.026). The sensitivity of MRD in diagnosis of lacrimal duct obstructive diseases was 97.4%, the specificity was 100%, the accuracy was 98.3%, the positive predictive value was 100% and the negative predictive value was 95.2% . According to 40 eyes of the control group, the mean value of the maximum cross-sectional area of the lacrimal sac was: (10.9 ± 0.4) mm(2). Twenty-two eyes underwent lacrimal endoscopy examination and the endoscopic findings were consistent with LMRH diagnosis. The lesions in the lacrimal duct displayed more clearly and intuitively than the LMRH, while LMRH had its unique advantages in showing the size of lacrimal sac, the mucosal thickness of lacrimal duct, large foreign bodies and lesions around the lacrimal duct. According to the results of LMRH and lacrimal endoscopy, 2 eyes of canalicular obstruction, 8 eyes of nasolacrimal duct stenosis, 20 eyes of nasolacrimal duct obstruction underwent lacrimal probing and stent implantation. Four eyes of nasolacrimal duct obstruction had drug treatment under lacrimal endoscopy. Thirty-eight eyes of chronic dacryocystitis underwent endonasal dacryocystorhinostomy. The other 6 eyes of chronic dacryocystitis underwent stent removal combined with endonasal dacryocystorhinostomy. CONCLUSIONS: LMRH is a noninvasive and reliable method to examine the lacrimal duct obstruction. It can better display the size of lacrimal sac, lacrimal mucosal thickness and surrounding soft tissues of lacrimal duct. It is also a good complementary method of lacrimal endoscopy and has guiding significance for individualized treatment in patients with lacrimal duct obstruction.

In vitro iron absorption of α-lactalbumin hydrolysate-iron and ß-lactoglobulin hydrolysate-iron complexes.

To study the feasibility of promoting iron absorption by peptides derived from α-lactalbumin and ß-lactoglobulin, the present work examined the transport of iron across Caco-2 monolayer cell as in vitro model. Caco-2 cells were seeded in bicameral chambers with α-lactalbumin hydrolysate-Fe (α-LAH-Fe) complex and ß-lactoglobulin hydrolysate-Fe (ß-LGH-Fe) complex, α-LAH and iron mixture, ß-LGH and iron mixture, FeSO4 and ascorbic acid mixture, and FeSO4. In addition, the cytotoxicity of α-LAH-Fe and ß-LGH-Fe complexes were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The iron absorption and ferritin content were assessed using the coupled in vitro digestion/Caco-2 cell model. Results support that peptide-iron complexes can promote ferritin formation and it is possible to apply ß-LGH-Fe complexes as iron-fortified supplements with high iron absorbability.

[Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice].

Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy: first-pass myocardial perfusion cardiovascular magnetic resonance imaging at 1.5 T.

AIM: To evaluate the integrity of the coronary microvasculature in patients with hypertrophic cardiomyopathy (HCM) using first-pass magnetic resonance perfusion imaging. MATERIALS AND METHODS: Twenty-two patients with HCM and 13 healthy volunteers underwent cardiac magnetic resonance imaging (CMR) at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late-phase contrast-enhanced imaging. Left ventricular end-diastolic wall thickness (EDTH), myocardial thickening, maximal upslope of time-intensity curve (slopemax), and late myocardial gadolinium enhancement (LGE) were assessed for each myocardial segment. The differences in slopemax, myocardial thickening, and EDTH between healthy volunteers and HCM patients were evaluated as were differences among hypertrophic segments of different severities (mild, moderate, and severe hypertrophy) in a one-way analysis of variance analysis. The differences in slopemax, myocardial thickening, and EDTH between the segments with and without LGE were compared by independent-sample t-test. A Pearson correlation test was used to determine the relationships between slopemax, EDTH, and myocardial thickening. RESULTS: Slopemax was statistically significantly less in HCM patients; the degree of myocardial thickening was also significantly reduced (p < 0.001). Slopemax and the degree of thickening statistically significantly decreased with increasing degrees of myocardial hypertrophy (p < 0.05). Differences in slopemax, myocardial thickening, and EDTH were observed between segments with and without LGE (p < 0.05). Slopemax and myocardial thickening were negatively correlated with EDTH. CONCLUSION: First-pass myocardial perfusion CMR with slopemax measurements demonstrates microvascular coronary dysfunction in patients with HCM, a determination that may aid in risk stratification, therapeutic planning, and determination of prognosis for HCM.

Bioconjugation of protein-repellent zwitterionic polymer brushes grafted from silicon nitride.

A new method for attaching antibodies to protein-repellent zwitterionic polymer brushes aimed at recognizing microorganisms while preventing the nonspecific adsorption of proteins is presented. The poly(sulfobetaine methacrylate) (SBMA) brushes were grafted from α-bromo isobutyryl initiator-functionalized silicon nitride (Si(x)N(4), x ≥ 3) surfaces via controlled atom-transfer radical polymerization (ATRP). A trifunctional tris(2-aminoethyl)amine linker was reacted with the terminal alkylbromide of polySBMA chains. N-Hydroxysuccinimide (NHS) functionalization was achieved by reacting the resultant amine-terminated polySBMA brush with bifunctional suberic acid bis(N-hydroxysuccinimide ester). Anti-Salmonella antibodies were subsequently immobilized onto polySBMA-grafted Si(x)N(4) surfaces through these NHS linkers. The protein-repellent properties of the polySBMA-grafted surface after antibody attachment were evaluated by exposing the surfaces to Alexa Fluor 488-labeled fibrinogen (FIB) solution (0.1 g·L(-1)) for 1 h at room temperature. Confocal laser scanning microscopy (CLSM) images revealed the minimal adsorption of FIB onto the antibody-coated polySBMA in comparison with that of antibody-coated epoxide monolayers and also bare Si(x)N(4) surfaces. Subsequently, the interaction of antibodies immobilized onto polySBMA with SYTO9-stained Salmonella solution without using blocking solution was examined by CLSM. The fluorescent images showed that antibody-coated polySBMA efficiently captured Salmonella with only low background noise as compared to antibody-coated monolayers lacking the polymer brush. Finally, the antibody-coated polySBMA surfaces were exposed to a mixture of Alexa Fluor 647-labeled FIB and Salmonella without the prior use of a blocking solution to evaluate the ability of the surfaces to capture bacteria while simultaneously repelling proteins. The fluorescent images showed the capture of Salmonella with no adsorption of FIB as compared to antibody-coated epoxide surfaces, demonstrating the potential of the zwitterionic layer in preventing the nonspecific adsorption of the proteins during the detection of bacteria in complex matrices.

Diagnostic performance of CUBE MRI sequences of the knee compared with conventional MRI.

AIM: To evaluate the efficacy and efficiency of three-dimensional (3D) fast spin-echo (FSE) with variable flip angle ("CUBE") magnetic resonance imaging (MRI) in knee imaging as compared with conventional MRI. MATERIALS AND METHODS: Twenty-nine patients (single knee) with joint injuries of varying degrees were enrolled in this study between January, 2011 and December, 2011. All patients underwent conventional MRI and a fat-suppressed CUBE MRI sequence. All patients subsequently underwent knee arthroscopic surgery performed by an experienced orthopaedic surgeon within 2 weeks after the MRI examinations. With standard reference provided by arthroscopic results, the sensitivity, specificity, and accuracy of both the CUBE and conventional MRI techniques were calculated for detecting cartilage lesions, meniscus tears, and anterior cruciate ligament injuries, respectively. A chi-square test was used for statistical analysis with a level of significance of p < 0.05. RESULTS: For the evaluation of articular cartilage lesions, the CUBE sequence had higher sensitivity (70.9% versus 50.6%, p < 0.01), higher specificity (72.6% versus 58.9%, p < 0.05), and higher accuracy (71.8% versus 55.2%, p = 0.001) than conventional MRI. For the evaluation of meniscus tears, CUBE and conventional MRI had similar sensitivity, specificity, and accuracy (p = 0.20-0.55). Similarly, there was no significant difference in sensitivity, specificity, or accuracy between CUBE imaging and conventional imaging in the detection of anterior cruciate ligament injuries (p = 0.13-0.65). CONCLUSION: CUBE MRI has similar or superior sensitivity, specificity, and accuracy to a conventional imaging protocol in the comprehensive evaluation of knee joint injuries.

Preparation and characterization of ß-lactoglobulin hydrolysate-iron complexes.

The purpose of this study was to determine the best preparation condition of ß-lactoglobulin hydrolysate-iron complexes and characterize its structural transformation both before and after binding using the UV-visible absorption spectrum, Fluorescence spectrum, and Fourier transform infrared spectroscopy. Results showed that ß-lactoglobulin hydrolysates obtained with alcalase after hydrolysis for 6h possessed the highest iron-binding capacity. The highest yield of complexes was obtained when the mass ratio between ß-lactoglobulin hydrolysate and Fe(3+) reached 40:1, with the optimal pH value of 7.0. All of the spectra indicated that some sites such as amido bonds transformed during chelation, and nitrogen atoms could chelate with Fe(3+) to form coordinate bonds by offering electron pairs. Therefore, ß-lactoglobulin hydrolysate-iron complexes may be good carriers for iron and possess great potential to be used as iron supplements.

Lysophosphatidic acid receptor 6 regulated by miR-27a-3p attenuates tumor proliferation in breast cancer.

PURPOSE: Lysophosphatidic acid (LPA) is a bioactive molecule which participates in many physical and pathological processes. Although LPA receptor 6 (LPAR6), the last identified LPA receptor, has been reported to have diverse effects in multiple cancers, including breast cancer, its effects and functioning mechanisms are not fully known. METHODS: Multiple public databases were used to investigate the mRNA expression of LPAR6, its prognostic value, and potential mechanisms in breast cancer. Western blotting was performed to validate the differential expression of LPAR6 in breast cancer tissues and their adjacent tissues. Furthermore, in vitro experiments were used to explore the effects of LPAR6 on breast cancer. Additionally, TargetScan and miRWalk were used to identify potential upstream regulating miRNAs and validated the relationship between miR-27a-3p and LPAR6 via real-time polymerase chain reaction and an in vitro rescue assay. RESULTS: LPAR6 was significantly downregulated in breast cancer at transcriptional and translational levels. Decreased LPAR6 expression in breast cancer is significantly correlated with poor overall survival, disease-free survival, and distal metastasis-free survival, particularly for hormone receptor-positive patients, regardless of lymph node metastatic status. In vitro gain and loss-of-function assays indicated that LPAR6 attenuated breast cancer cell proliferation. The analyses of TCGA and METABRIC datasets revealed that LPAR6 may regulate the cell cycle signal pathway. Furthermore, the expression of LPAR6 could be positively regulated by miR-27a-3p. The knockdown of miR-27a-3p increased cell proliferation, and ectopic expression of LPAR6 could partly rescue this phenotype. CONCLUSION: LPAR6 acts as a tumor suppressor in breast cancer and is positively regulated by miR-27a-3p.

Stable protein-repellent zwitterionic polymer brushes grafted from silicon nitride.

Zwitterionic poly(sulfobetaine acrylamide) (SBMAA) brushes were grafted from silicon-rich silicon nitride (SixN4, x > 3) surfaces by atom transfer radical polymerization (ATRP) and studied in protein adsorption experiments. To this aim ATRP initiators were immobilized onto SixN4 through stable Si-C linkages via three consecutive reactions. A UV-induced reaction of 1,2-epoxy-9-decene with hydrogen-terminated SixN4 surfaces was followed by conversion of the epoxide with 1,2-ethylenediamine resulting in primary and secondary amine-terminated surfaces. A reaction with 2-bromoisobutyryl bromide led to ATRP initiator-covered surfaces. Zwitterionic polymer brushes of SBMAA were grown from these initiator-coated surfaces (thickness ∼30 nm), and the polymer-coated surfaces were characterized in detail by static water contact angle measurements, X-ray photoelectron spectroscopy (XPS), and an atomic force microscope (AFM). The adsorption of proteins onto zwitterionic polymer coated surfaces was evaluated by in situ reflectometry, using a fibrinogen (FIB) solution of 0.1 g·L(-1), and compared to hexadecyl-coated SixN4 surfaces (C16-SixN4), uncoated air-based plasma oxidized SixN4 surfaces (SiOy-SixN4), and hexa(ethylene oxide)-coated SixN4 surfaces (EO6-SixN4). Excellent protein repellence (>99%) was observed for these zwitterionic polymer-coated SixN4 surfaces during exposure to FIB solution as compared to C16-SixN4 surfaces. Furthermore, the stability of these zwitterionic polymer-coated SixN4 surfaces was surveyed by exposing the surfaces for 1 week to phosphate buffered saline (PBS) solution at room temperature. The zwitterionic polymer-coated SixN4 surfaces before and after exposure to PBS solution were characterized by XPS, AFM, and water contact angle measurements, and their protein-repelling properties were evaluated by reflectometry. After exposure to PBS solution, the zwitterionic polymer coating remained intact, and its thickness was unchanged within experimental error. No hydrolysis was observed for the zwitterionic polymer after 1 week exposure to PBS solution, and the surfaces still repelled 98% FIB as compared to C16-SixN4 surfaces, demonstrating the long-term efficiency of these easily prepared surface coatings.

Electroacupuncture prevents cocaine-induced conditioned place preference reinstatement and attenuates ΔFosB and GluR2 expression.

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.

[Consistency of peripheral whole blood and venous serum procalcitonin in children: a multicenter parallel controlled study].

Objective: To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection. Methods: This multicenter cross-sectional parallel control study was conducted in 11 children's hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman's rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection. Results: A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum (r=0.97, P<0.01). The linear regression equation was PCTvenous serum=0.135+0.929×PCTperipheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods (r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 µg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 µg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 µg/L, respectively. Conclusions: There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

Development and Validation of a Preference-Based Glaucoma Utility Instrument Using Discrete Choice Experiment.

IMPORTANCE: A glaucoma-specific instrument for estimating utilities across the spectrum of glaucoma severity is currently lacking, hindering the assessment of the cost-effectiveness of glaucoma treatments. OBJECTIVE: To develop and validate the preference-based Glaucoma Utility Instrument (Glau-U) and to ascertain the association between Glau-U utilities and severity of glaucoma and vision impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted in 2 stages at the Singapore National Eye Centre glaucoma clinics. Stage 1 focused on the identification and pretesting of the Glau-U attributes and was carried out between June 2009 and May 2016. Stage 2 involved the development and administration of the discrete choice experiment (DCE) survey and tasks and was conducted between May 7, 2018, and December 11, 2019. Stage 2 participants were English- or Mandarin-speaking Singaporean citizens or permanent residents of Chinese, Malay, or Indian ethnicity who were 40 years or older and had a clinical diagnosis of glaucoma in at least 1 eye. EXPOSURES: Glau-U comprised 6 quality-of-life attributes: activities of daily living, lighting and glare, movement, eye discomfort, other effects of glaucoma, and social and emotional effects. The descriptions or response options for these attributes were no difficulty or never, some difficulty or sometimes, or severe difficulty or often. MAIN OUTCOMES AND MEASURES: Utility weights for Glau-U were developed using a DCE questionnaire, which was interviewer administered to participants. Mixed logit regression determined utility weights for each health state. Glau-U utility weights across better- or worse-eye glaucoma and vision impairment severity were calculated using 1-way analysis of variance. Correlations between Glau-U utilities and better- or worse-eye visual fields and EuroQol 5-Dimension utilities were ascertained to assess convergent and divergent validity. RESULTS: Of the 304 participants (mean [SD] age, 68.3 [8.7] years; 182 men [59.9%]), 281 (92.4%) had no vision impairment in the better eye, 13 (4.3%) had mild impairment, and 10 (3.3%) had moderate to severe vision impairment. Mean (SD) Glau-U utilities decreased as better-eye glaucoma severity increased (none: 0.73 [0.21]; mild: 0.66 [0.21]; moderate: 0.66 [0.20]; severe: 0.60 [0.28]; and advanced or end-stage: 0.22 [0.38]; P < .001), representing reductions of 20.7% to 76.1% in quality-adjusted life-years compared with a health state that included preperimetric glaucoma. Mean (SD) Glau-U utilities also decreased as better-eye vision impairment worsened from 0.67 (0.23) for none to 0.58 (0.32) for mild to 0.46 (0.29) for moderate to severe vision impairment. Glau-U utilities demonstrated moderate correlations with better-eye (r = 0.34; P < .001) and worse-eye (r = 0.33; P < .001) mean deviation scores and low correlations with EuroQol 5-Dimension utilities (r = 0.22; P < .001), supporting convergent and divergent validity. CONCLUSIONS AND RELEVANCE: Use of Glau-U revealed large decrements in utility that were associated with late-stage glaucoma, suggesting that this new instrument may be useful for cost-effectiveness analyses of interventions and informing resource allocation policies for glaucoma and vision loss.

20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits.

BACKGROUND: Wolff-Parkinson-White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. METHODS AND RESULTS: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. CONCLUSIONS: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.

Functional conservation of an insect odorant receptor gene across 250 million years of evolution.

Pest insects have a profound negative impact on agriculture and human health. Significant global losses of crops, stored agricultural products, timber and livestock can be attributed to damage and destruction by insects . Blood-feeding insects such as mosquitoes, flies and ticks transmit many of humanity's most devastating infectious diseases. Insect-borne diseases account for more than one million annual fatalities, and insect-associated illnesses surpass 300 million annual reported cases . The medical and economic impact of these animals can be ascribed in part to the sensitivity and selectivity of their olfactory systems, essential for location of their preferred plant and animal hosts.

Feasibility of a simple microsieve-based immunoassay platform.

The intrinsic properties of silicon microsieves, such as an optically flat surface, high overall porosity, and low flow resistance have led to an increasing number of biotechnology applications. In this report, the feasibility of creating a microsieve-based immunoassay platform was explored. Microsieves containing 5µm pores were coupled with poly-acrylic acid chains, and then mounted into a plastic holder to enable rapid reagent exchanges via a wicking mechanism. The mounted microsieves were coated with infectious disease-related antigens at [2.5 and 25µg/mL], [20 and 50µg/mL], and [20 and 100µg/mL] to facilitate detection of serum-derived human antibodies against Rubella (3-day measles), B. burgdorferi (Lyme disease), or T. pallidum (syphilis), respectively. The prototype microsieve-based immunoassay platform was able to distinguish positive control sera containing antibodies against Rubella, T. pallidum, and B. burgdorferi from negative control sera with similar qualitative results as FDA-approved ELISA tests. Testing of a WHO IgG syphilitic standard at 0.3, 0.15, 0.075, 0.0375, and 0.01875IU/mL demonstrated that the T. pallidum microsieve assay is able to distinguish disease-specific IgG signal from background signal at similar, and possibly lower, levels than the corresponding ELISA. The T. pallidum microsieve assay prototype also differentiated positive clinical serum samples from negative donor samples, and the results were in good agreement with ELISA (R(2)=0.9046). These feasibility studies demonstrate the potential for utilizing microsieves, along with a reagent wicking device, as a simple diagnostic immunoassay platform.