[Efficacy analysis of high-sensitivity troponin I concentration and its changes in the diagnosis of acute myocardial infarction].

Objective: To explore the feasibility and accuracy of 0-1 h high sensitivity cardiac troponin I (hs-cTnI) concentration and its changes in judging non-ST segment elevation myocardial infarction (NSTEMI), and to investigate the feasibility of a simplified process. Methods: Patients with acute chest pain and suspected NSTEMI who were admitted to the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were selected. Hs-cTnI test was carried out for the selected patients at the time of visit (0 h) and 1 h after visit. According to the 0-1 h hs-cTnI diagnostic process and threshold standard recommended by European Society of Cardiology (ESC) guidelines in 2015, the laboratory adjudication was determined. Cardiologists who did not participate in the project design and did not know the results of hs-cTnI test performed the clinical judgment according to the routine diagnosis and treatment process of emergency department. Taking clinical judgment as the gold standard, the diagnostic efficacy of 0-1 h hs-cTnI concentration and its change recommended by the guidelines for judging NSTEMI in Chinese population was analyzed. The guide process was simplified. Under the condition of not considering the time of chest pain, the guideline threshold was used for test and judgement, and the diagnostic efficacy of the simplified process was evaluated. Results: A total of 1 534 patients were enrolled in the study, aged (62±12) years and 952 (62.1%) patients were male. Among them, 402 patients (26.2%) were clinically diagnosed as NSTEMI and 1 132 patients (73.8%) were diagnosed as non-NSTEMI. According to the diagnosis and determination process recommended by the guidelines, NSTEMI was excluded in 672 patients (42.8%), and 464 patients (30.2%) were diagnosed as NSTEMI. The consistency rate with clinical determination reached 92.4% (1 050/1 136), the sensitivity of excluding diagnosis was 99.5% (95%CI: 98.0%-99.9%), the negative predictive value was 99.7% (95%CI: 98.8%-99.9%), and the negative likelihood ratio was 0.008 (95%CI: 0.002-0.335). The diagnostic specificity was 92.6% (95%CI: 90.9%-94.0%), the positive predictive value was 81.9% (95%CI: 78.0%-85.2%), and the positive likelihood ratio was 12.739 (95%CI: 10.356-15.670). According to the simplified process, NSTEMI was excluded in 675 patients (44.0%), and 463 patients (30.2%) were diagnosed as NSTEMI. The consistency rate with clinical judgment was 92.4% (1 051/1 138), the sensitivity of exclusion diagnosis was 99.3% (95%CI: 97.6%-99.8%), the negative predictive value was 99.6% (95%CI: 98.6%-99.9%), and the negative likelihood ratio was 0.012 (95%CI: 0.004-0.389). The diagnostic specificity was 92.6% (95%CI: 90.9%-94.0%), the positive predictive value was 81.9% (95%CI: 78.0%-85.2%), and the positive likelihood ratio was 12.705 (95%CI: 10.328-15.630). There was no significant difference in diagnostic efficacy between the simplified process and the recommended process (all P>0.05). Conclusion: The diagnostic process for judging NSTEMI according to the 0-1 h hs-cTnI concentration and its change criteria recommended by the 2015 ESC guidelines is applicable in the Chinese population and remains highly accurate in judging NSTEMI without considering the duration of chest pain at the time of presentation.

[Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure].

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.

Adult Age Estimation of CT Image Reconstruction of the Laryngeal Cartilages and Hyoid Bone Based on Data Mining.

ABSTRACT: Objective To explore the feasibility of the CT image reconstruction of laryngeal cartilage and hyoid bone in adult age estimation using data mining methods. Methods The neck thin slice CT scans of 413 individuals aged 18 to <80 years were collected and divided into test set and train set, randomly. According to grading methods such as TURK et al., all samples were graded comprehensively. The process of thyroid cartilage ossification was divided into 6 stages, the process of cricoid cartilage ossification was divided into 5 stages, and the synosteosis between the greater horn of hyoid and hyoid body was divided into 3 stages. Multiple linear regression model, support vector regression model, and Bayesian ridge regression model were developed for adult age estimation by scikit-learn 0.17 machine learning kit （Python language）. Leave-one-out cross-validation and the test set were used to further evaluate performance of the models. Results All indicators were moderately or poorly associated with age. The model with the highest accuracy in male age estimation was the support vector regression model, with a mean absolute error of 8.67 years, much higher than the other two models. The model with the highest accuracy in female adult age estimation was the support vector regression model, with a mean absolute error of 12.69 years, but its accuracy differences with the other two models had no statistical significance. Conclusion Data mining technology can improve the accuracy of adult age estimation, but the accuracy of adult age estimation based on laryngeal cartilage and hyoid bone is still not satisfactory, so it should be combined with other indicators in practice.

[Research Progress of Adult Age Determination with Imaging Methods].

ABSTRACT: Adult age determination plays an important role in individual identification, criminal investigation and social welfare. The most popular adult age determination indicators are pubic symphysis, iliac auricular surface, costal cartilage, cranial sutures, teeth, laryngeal cartilage, etc. In recent years, with the progress of CT imaging and 3D reconstruction technology, the adult age determination study gradually has transferred from a time-consuming general observation of bones with complex pre-processing in the past to the non-destructive, convenient, time-saving and easy to store image analysis technology. To explore more accurate, rapid and convenient adult age determination methods, multiple imaging methods and artificial intelligence have been applied in adult age determination. This paper reviews the common methods and research progress of adult age determination at home and abroad, infers the development direction of adult age determination, in order to provide reference for the improvement and optimization of forensic adult age determination.

[Estimation of Sex from Patella Measurements in Sichuan Han Population Based on CT-Three-Dimensional Volume Reconstruction Technique].

ABSTRACT: Objective To estimate sex based on patella measurements of Sichuan Han population by computed tomography three-dimensional volume reconstruction technique, and to explore the application value of patella in sex estimation. Methods CT three-dimensional volume reconstruction images of patella of 250 individuals were collected, the four measurement indicators including patellar length, patellar width, patellar thickness, and patellar volume were measured. The t-test was used to determine measurement indicators with sex differences. Fisher discriminant analysis was used to establish the sex discriminant function and the prediction accuracy was calculated by leave-one-out cross validation. Results The sex differences of the four measurement indicators had a statistical significance （P<0.05）. The accuracy rate of the univariate discriminant function established by the patellar length was the highest （82.0%）. The accuracy rates of the all indicators discriminant function and the stepwise discriminant function were 80.4% and 81.6%, respectively. Conclusion It is feasible and accurate to estimate sex of Sichuan Han population by patella measurements with CT three-dimensional volume reconstruction technique. The method may be used as an alternative for sex estimation of Sichuan Han population when other bones with higher accuracy are not available.

Age Estimation in Han Adults by Thin-Layer CT Scan of Cranial Sutures.

ABSTRACT: Objective To explore the value of degree of cranial suture closure in forensic adult age estimation by thin-layer CT scan and establish an adult age estimation model of the Han nationality. Methods Thin-layer CT scan samples of the heads of 220 healthy Sichuan Han adults （110 males, 110 females） aged 20 to 70 were collected, of which 20 samples （10 males, 10 females） were randomly selected as test samples. The sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） were respectively and equally divided into 2 segments, and every segment was equally divided into 10 layers and the corresponding multiplanar reformation （MPR） images were selected. The closure of cranial sutures on MPR images was classified into the grades 1-7. The correlations between cranial sutures and age were analyzed to build regression equation for age estimation. Results The degree of closure of sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） was positively correlated with age. The coefficient of determination （R2） of regression equation was 0.419 in males, 0.589 in females, and 0.522 in all samples. The results of the verification test showed that the mean absolute error （MAE） was 6.39 years in males, 6.16 years in females, and 6.29 years in all samples. Conclusion There was a higher accuracy in adult age estimation by thin-layer CT scan of cranial sutures. The age of Han nationality adults can be estimated by the degree of cranial sutures closure.

Laser picoscopy of valence electrons in solids.

Valence electrons contribute a small fraction of the total electron density of materials, but they determine their essential chemical, electronic and optical properties. Strong laser fields can probe electrons in valence orbitals1-3 and their dynamics4-6 in the gas phase. Previous laser studies of solids have associated high-harmonic emission7-12 with the spatial arrangement of atoms in the crystal lattice13,14 and have used terahertz fields to probe interatomic potential forces15. Yet the direct, picometre-scale imaging of valence electrons in solids has remained challenging. Here we show that intense optical fields interacting with crystalline solids could enable the imaging of valence electrons at the picometre scale. An intense laser field with a strength that is comparable to the fields keeping the valence electrons bound in crystals can induce quasi-free electron motion. The harmonics of the laser field emerging from the nonlinear scattering of the valence electrons by the crystal potential contain the critical information that enables picometre-scale, real-space mapping of the valence electron structure. We used high harmonics to reconstruct images of the valence potential and electron density in crystalline magnesium fluoride and calcium fluoride with a spatial resolution of about 26 picometres. Picometre-scale imaging of valence electrons could enable direct probing of the chemical, electronic, optical and topological properties of materials.

Research Progress on Automatic Assessment of Bone Age.

ABSTRACT: Bone age is an important indicator of human growth and development, which can objectively reflect the growth level and maturity of individuals. Traditional manual bone age assessment usually compares the X-ray of the left wrist with the reference standard to obtain the corresponding bone age. This method is time-consuming and its results vary with different observers. In recent years, with the continuous development of computer science, bone age assessment has began to change from traditional manual assessment to automatic assessment. Although there has already been numerous researches on automatic bone age assessment, most of them are still in the experimental stage. This paper reviews related research and progress on automatic bone age assessment at home and abroad in recent years, in order to provide reference and research ideas for relevant researchers.

Cost-effectiveness analysis of the addition of bevacizumab to chemotherapy as induction and maintenance therapy for metastatic non-squamous non-small-cell lung cancer

Background. The BEYOND trial found that the addition of bevacizumab (B) to paclitaxel-carboplatin (PC) chemotherapy provided a significant clinical benefit to Chinese patients with metastatic non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of adding B to first-line PC induction and continuation maintenance therapy from a Chinese perspective. Methods. A Markov model was developed to estimate the cost and effectiveness of B + PC in the induction and maintenance therapy of patients with metastatic non-squamous NSCLC. Costs were calculated in the Chinese setting, and health outcomes derived from the BEYOND trial were measured as quality-adjusted life years (QALYs). A one-way sensitivity analysis was conducted to explore the impact of various parameters in the study. Results. The B + PC treatment was more costly ($112,943.40 versus $32,171.43) and more effective (1.07 QALYs versus 0.80 QALYs) compared with the PC treatment. Adding B to the PC regimen for non-squamous NSCLC results in an incremental cost-effectiveness ratio of $299,155.44 per QALY, which exceeded the accepted societal willingness-to-pay threshold ($23,970.00) for China. In the sensitivity analysis, the duration of progression-free survival (PFS) for the B + PC group, the cost of the PFS state for B + PC group and the price of B were considered the most sensitive factors in the model. Conclusions. The addition of B to first-line PC induction and maintenance therapy was not determined to be a cost-effective strategy for metastatic non-squamous NSCLC in China, even when an assistance program was provided (AU)

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Cost-effectiveness analysis of the addition of bevacizumab to chemotherapy as induction and maintenance therapy for metastatic non-squamous non-small-cell lung cancer.

BACKGROUND: The BEYOND trial found that the addition of bevacizumab (B) to paclitaxel-carboplatin (PC) chemotherapy provided a significant clinical benefit to Chinese patients with metastatic non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of adding B to first-line PC induction and continuation maintenance therapy from a Chinese perspective. METHODS: A Markov model was developed to estimate the cost and effectiveness of B + PC in the induction and maintenance therapy of patients with metastatic non-squamous NSCLC. Costs were calculated in the Chinese setting, and health outcomes derived from the BEYOND trial were measured as quality-adjusted life years (QALYs). A one-way sensitivity analysis was conducted to explore the impact of various parameters in the study. RESULTS: The B + PC treatment was more costly ($112,943.40 versus $32,171.43) and more effective (1.07 QALYs versus 0.80 QALYs) compared with the PC treatment. Adding B to the PC regimen for non-squamous NSCLC results in an incremental cost-effectiveness ratio of $299,155.44 per QALY, which exceeded the accepted societal willingness-to-pay threshold ($23,970.00) for China. In the sensitivity analysis, the duration of progression-free survival (PFS) for the B + PC group, the cost of the PFS state for B + PC group and the price of B were considered the most sensitive factors in the model. CONCLUSIONS: The addition of B to first-line PC induction and maintenance therapy was not determined to be a cost-effective strategy for metastatic non-squamous NSCLC in China, even when an assistance program was provided.

Impaired p65 degradation by decreased chaperone-mediated autophagy activity facilitates epithelial-to-mesenchymal transition.

Aberrant activation of nuclear factor-κB (NF-κB) has been observed in a wide range of human cancers and is thought to promote tumorigenesis and metastasis. As a central component of NF-κB pathway, p65 protein level is tightly regulated and could be subjected to proteasome degradation. Here we demonstrated that p65 can bind to HSC70 with four consensus recognition motif in its RHD domain and be constitutively transported to the lysosome membrane to bind with lysosome-associated membrane protein type 2A and degraded within the lysosome in two epithelial cell lines, proposing that p65 can be degraded by chaperone-mediated autophagy (CMA). Of great importance, there is a decreased CMA activity together with impaired degradation of p65 in a process of epithelial-mesenchymal transition (EMT). The resulted accumulation of p65 leads to higher NF-κB activity and contributes to the progression and maintenance of the EMT program. Taken together, our results define a novel regulatory mechanism for the important transcription factor p65, and these findings would shed new light on the inhibition of EMT, as well as metastasis of cancer cells.

Molecular cloning and characterization of a short peptidoglycan recognition protein from silkworm Bombyx mori.

Peptidoglycan is the major bacterial component recognized by the insect immune system. Peptidoglycan recognition proteins (PGRPs) are a family of pattern-recognition receptors that recognize peptidoglycans and modulate innate immune responses. Some PGRPs retain N-acetylmuramoyl-L-alanine amidase (Enzyme Commission number: 3.5.1.28) activity to hydrolyse bacterial peptidoglycans. Others have lost the enzymatic activity and work only as immune receptors. They are all important modulators for innate immunity. Here, we report the cloning and functional analysis of PGRP-S4, a short-form PGRP from the domesticated silkworm, Bombyx mori. The PGRP-S4 gene encodes a protein of 199 amino acids with a signal peptide and a PGRP domain. PGRP-S4 was expressed in the fat body, haemocytes and midgut. Its expression level was significantly induced by bacterial challenges in the midgut. The recombinant PGRP-S4 bound bacteria and different peptidoglycans. In addition, it inhibited bacterial growth and hydrolysed an Escherichia coli peptidoglycan in the presence of Zn2+ . Scanning electron microscopy showed that PGRP-S4 disrupted the bacterial cell surface. PGRP-S4 further increased prophenoloxidase activation caused by peptidoglycans. Taken together, our data suggest that B. mori PGRP-S4 has multiple functions in immunity.

Multi-petahertz electronic metrology.

The frequency of electric currents associated with charge carriers moving in the electronic bands of solids determines the speed limit of electronics and thereby that of information and signal processing. The use of light fields to drive electrons promises access to vastly higher frequencies than conventionally used, as electric currents can be induced and manipulated on timescales faster than that of the quantum dephasing of charge carriers in solids. This forms the basis of terahertz (1012 hertz) electronics in artificial superlattices, and has enabled light-based switches and sampling of currents extending in frequency up to a few hundred terahertz. Here we demonstrate the extension of electronic metrology to the multi-petahertz (1015 hertz) frequency range. We use single-cycle intense optical fields (about one volt per ångström) to drive electron motion in the bulk of silicon dioxide, and then probe its dynamics by using attosecond (10-18 seconds) streaking to map the time structure of emerging isolated attosecond extreme ultraviolet transients and their optical driver. The data establish a firm link between the emission of the extreme ultraviolet radiation and the light-induced intraband, phase-coherent electric currents that extend in frequency up to about eight petahertz, and enable access to the dynamic nonlinear conductivity of silicon dioxide. Direct probing, confinement and control of the waveform of intraband currents inside solids on attosecond timescales establish a method of realizing multi-petahertz coherent electronics. We expect this technique to enable new ways of exploring the interplay between electron dynamics and the structure of condensed matter on the atomic scale.

Genetic relationships analysis of olive cultivars grown in China.

The olive tree is an iconic tree of the Mediterranean, and is used extensively to produce high-quality olive oil. Although the China olive industry has just begun to be valued, there were also existed mislabeling and synonyms in introduced cultivars. The aim of this study was to analyze genetic similarities among olive cultivars in China using SSR and ISSR techniques. Thirty-two samples were collected from Xichang. Five of these cultivars were issued from a Chinese breeding program. Genomic DNA samples were extracted from young leaves and PCR was used to generate SSR and ISSR markers. A total of 107 polymorphic bands were detected on thirteen SSR loci, with an average of eight alleles per locus. The observed heterozygosity ranged from 0.785 (DCA03) to 0.990 (GAPU47), and the expected heterozygosity varied between 0.782 (DCA03) and 0.940 (GAPU103A). The discrimination power ranged from 0.57 to 0.83, while the polymorphism information content values ranged from 0.768 (DCA03) to 0.934 (GAPU103A). Nine ISSR primers generated 85 reproducible bands of which 78 (91.8%) were polymorphic. Based on our data, genetic similarity between cultivars ranged from 0.57 to 0.83. Cluster analysis revealed that 32 cultivars were clustered into six groups, which supports similar morphology such as use, oil content and fruit weight but not similar geographical origins. Our data also allow the identification of unknown cultivars and cases of synonyms.

Renal expression of advanced oxidative protein products predicts progression of renal fibrosis in patients with IgA nephropathy.

Predicting the risk of disease progression in IgA nephropathy (IgAN) remains a challenge. This study was conducted to test the hypothesis that renal accumulation of advanced oxidized protein products (AOPPs) is an early predictor for renal progression in IgAN. This was a single-center prospective cohort study. One hundred IgAN patients with eGFR>80 ml/min/1.73 m(2) were enrolled. Seventy-seven patients were followed for a mean of 4.2 years, and 30 patients received repeat renal biopsy at a mean of 42 months after diagnosis. The outcomes were the progression of renal fibrosis and rapid progression of CKD (>5 ml/min/1.73 m(2)/year) during follow-up. Immunoreactivity of AOPPs was detected predominantly in tubular epithelial cells and co-localized with expression of TGF-ß1 and angiotensin II. Renal staining score of AOPPs at diagnosis was associated with the level of tissue cellular inflammation. Accumulation of AOPPs, particularly in interstitial-infiltrating cells, was negatively correlated with changes of eGFR during follow-up; those with expression scores greater than the median at diagnosis had significantly higher incidences of rapid decline of eGFR compared with those with the score less than or equal to the median. For patients who received repeat renal biopsy, renal AOPP levels greater than the median at diagnosis were associated with increase in renal fibrosis index at repeat biopsy. After multivariate adjustment, renal AOPP expression was an independent predictor for progression of renal fibrosis and rapid decline of eGFR. Taken together, these results demonstrate that renal AOPPs might be a predictor, detectable at the time of diagnosis, for renal progression in patients with early stage IgAN.

Predictors of early treatment discontinuation in a cohort of patients treated with boceprevir-based therapy for hepatitis C infection.

In this real-world cohort, 49% of patients stopped boceprevir-based hepatitis C therapy early, with only 20% stopping due to treatment futility. Having more comorbidities was significantly associated with early discontinuation. Tolerability of boceprevir-based regimens may be substantially worse than reported in clinical trials, particularly for patients with comorbidities.

USA300 methicillin-resistant S. aureus (USA300 MRSA) colonization and the risk of MRSA infection in residents of extended-care facilities.

To examine the pathogenesis of USA300 MRSA infection in long-term care residents, we performed a retrospective cohort study of 1691 adult residents of two extended-care facilities from 2003 to 2007 to assess whether the risk of subsequent MRSA infection is higher in USA300 MRSA-colonized residents compared to non-colonized residents or non-USA300 MRSA colonized residents. Six per cent of residents were colonized with USA300 MRSA; 12% of residents were colonized with non-USA300 MRSA; and 101 residents developed MRSA infection. The risk of infection was twofold higher in residents colonized with USA300 MRSA compared to residents not colonized with MRSA [adjusted hazard ratio 2·3, 95% confidence interval (CI) 1·1-4·5]. The risk of infection in USA300 MRSA-colonized residents was similar to USA300 MRSA non-colonized residents (relative risk 1·1, 95% CI 0·5-2·3). Our findings show that colonization with USA300 MRSA increases the risk of MRSA infection suggesting a similar pathogenesis.

Albumin overload activates intrarenal renin-angiotensin system through protein kinase C and NADPH oxidase-dependent pathway.

OBJECTIVE: Inappropriate activation of the intrarenal renin-angiotensin system (RAS) plays an important role in the pathogenesis of hypertension and renal injury. However, the underlying mechanisms remain elusive. Proteinuria has been shown to elicit the renal activation of RAS. The present study was performed to test the intracellular signal pathway involved in albumin-triggered activation of RAS. DESIGN AND METHODS: NRK52E cells, a rat renal proximal tubular cell line, were incubated with increased levels of albumin. The rat model of protein overload was established in female Wistar-Kyoto rats that were subjected to unilateral nephrectomy followed by daily intraperitoneal injection of BSA at various doses (0.5, 1.0, and 5.0 g/kg) or combination with intragastric administration of apocynin (100 mg/kg per day), an inhibitor of NADPH oxidase. RESULTS: Exposure of the cells to high levels of albumin activated the RAS through the endocytic receptors megalin and cubilin. High levels of albumin triggered the production of intracellular reactive oxygen species by a protein kinase C (PKC)-NADPH oxidase-dependent pathway and this, in turn, led to activation of nuclear factor-κB (NF-κB) and activation protein-1 (AP-1). Inhibition of PKC or NADPH oxidase abolished albumin-induced activation of RAS. In a protein overload rat model, activation of RAS in renal proximal tubular cells was significantly increased, coincident with activation of PKC, NADPH oxidase, NF-κB, and AP-1. Chronic inhibition of NADPH oxidase by apocynin largely ameliorated intrarenal activation of RAS. CONCLUSION: Exposure of renal tubular epithelial cells with high levels of albumin triggers activation of RAS via a PKC-NADPH oxidase-dependent pathway.

Serum protein signatures detect early radiographic osteoarthritis.

OBJECTIVE: To test the hypothesis that early knee and hand osteoarthritis (OA) development is characterized by detectable changes in serum proteins relevant to inflammation, cell growth, activation, and metabolism several years before OA becomes radiographically evident. METHODS: Using microarray platforms that simultaneously test 169 proteins relevant to inflammation, cell growth, activation and metabolism, we conducted a case-control study nested within the Baltimore Longitudinal Study of Aging (BLSA). Subjects included 22 incident cases of OA and 66 age-, sex- and body mass index (BMI)-matched controls. Serum samples tested were obtained at the time of radiographic classification as either case or control, and up to 10 years earlier at a time when all participants were free of radiographic OA. Proteins with mean signal intensities fourfold higher than background were compared between cases and controls using multivariate techniques. RESULTS: Sixteen proteins were different between OA cases compared to controls. Four of these proteins [matrix metalloproteinase (MMP)-7, interleukin (IL)-15, plasminogen activator inhibitor (PAI)-1 and soluble vascular adhesion protein (sVAP)-1] were already different in samples obtained 10 years before radiographic classification and remained different at the time of diagnosis. Six additional proteins were only associated with subsequent OA development and not with established OA. CONCLUSIONS: Changes in serum proteins implicated in matrix degradation, cell activation, inflammation and bone collagen degradation products accompany early OA development and can precede radiographic detection by several years.

Matter-wave self-imaging by atomic center-of-mass motion induced interference.

We demonstrate matter-wave self-imaging resulting from atomic center-of-mass motion-based interference. We show that non-negligible atomic center-of-mass motion and an instantaneous Doppler shift can drastically change the condensate momentum distribution, resulting in a periodic collapse and the recurrence of condensate diffraction probability as a function of the stationary light-field pulsing time. The observed matter-wave self-imaging is characterized by an atomic center-of-mass motion induced population amplitude interference in the presence of the light field that simultaneously minimizes all high (n>or=1) diffraction orders and maximizes the zeroth diffraction component.