There is increasing evidence showing that the stromal cells surrounding cancer epithelial cells, rather than being passive bystanders, might have a role in modifying tumor outgrowth. The molecular basis of this aspect of carcinoma etiology is controversial. Some studies have reported a high frequency of genetic aberrations in carcinoma-associated fibroblasts (CAFs), whereas other studies have reported very low or zero mutation rates. Resolution of this contentious area is of critical importance in terms of understanding both the basic biology of cancer as well as the potential clinical implications of CAF somatic alterations. We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis of CAFs derived from breast and ovarian carcinomas using a 500K SNP array platform. Our data show conclusively that LOH and copy number alterations are extremely rare in CAFs and cannot be the basis of the carcinoma-promoting phenotypes of breast and ovarian CAFs.
The authors conducted a 2-year follow-up of 40 cardiovascular disease patients (mean age = 65.6 years (standard deviation, 5.8)) who underwent repeated measurements of cardiovascular response before and during the 2008 Beijing Olympics (Beijing, China), when air pollution was strictly controlled. Ambient levels of particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5), black carbon, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were measured continuously, with validation of concurrent real-time measurements of personal exposure to PM2.5 and carbon monoxide. Linear mixed-effects models were used with adjustment for individual risk factors, time-varying factors, and meteorologic effects. Significant heart rate variability reduction and blood pressure elevation were observed in association with exposure to air pollution. Specifically, interquartile-range increases of 51.8 µg/m3, 2.02 µg/m3, and 13.7 ppb in prior 4-hour exposure to PM2.5, black carbon, and nitrogen dioxide were associated with significant reductions in the standard deviation of the normal-to-normal intervals of 4.2% (95% confidence interval (CI): 1.9, 6.4), 4.2% (95% CI: 1.8, 6.6), and 3.9% (95% CI: 2.2, 5.7), respectively. Greater heart rate variability declines were observed among subjects with C-reactive protein values above the 90th percentile, subjects with a body mass index greater than 25, and females. The authors conclude that autonomic and vascular dysfunction may be one of the mechanisms through which air pollution exposure can increase cardiovascular disease risk, especially among persons with systemic inflammation and overweight.
air pollution; carbon; heart rate; inflammation; obesity; particulate matter; soot
The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a poorly understood key event in breast tumor progression. Here, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a model of human DCIS and primary breast tumors. Progression to invasion was promoted by fibroblasts and inhibited by normal myoepithelial cells. Molecular profiles of isolated luminal epithelial and myoepithelial cells identified an intricate interaction network involving TGFβ, Hedgehog, cell adhesion, and p63 required for myoepithelial cell differentiation, the elimination of which resulted in loss of myoepithelial cells and progression to invasion.
Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations, and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its functions and thus cancer risk. In the current, hospital-based case-control study of 471 cervical cancer cases and 600 sex and age frequency-matched cancer-free controls in an Eastern Chinese population, we genotyped two common polymorphisms in the MKK4 promoter region (-1304T>G, rs3826392 and -1044A>T, rs3809728)c and assessed their associations with the risk of cervical cancer. We found that compared with the most common -1304TT genotype, carriers of -1304G variant genotypes had a significantly decreased risk of cervical cancer [odds ratio (OR)=0.71; 95% confidence interval (CI)=0.53–0.92 for TG, and OR=0.52; 95%CI=0.30–0.91 for GG] in an allele dose-response manner (adjusted Ptrend=0.004). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 mRNA expression levels of the G variant carriers was significantly higher in tumor tissues than those of the -1304TT genotype. However, no significant association was observed between the -1044A>T polymorphism and risk of cervical cancer. Our data suggest that the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of cervical cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to cervical cancer.
A wide array of microorganisms survive and thrive in extreme environments. However, we know little about the patterns of, and controls over, their large-scale ecological distribution. To this end, we have applied a bar-coded 16S rRNA pyrosequencing technology to explore the phylogenetic differentiation among 59 microbial communities from physically and geochemically diverse acid mine drainage (AMD) sites across Southeast China, revealing for the first time environmental variation as the major factor explaining community differences in these harsh environments. Our data showed that overall microbial diversity estimates, including phylogenetic diversity, phylotype richness and pairwise UniFrac distance, were largely correlated with pH conditions. Furthermore, multivariate regression tree analysis also identified solution pH as a strong predictor of relative lineage abundance. Betaproteobacteria, mostly affiliated with the ‘Ferrovum' genus, were explicitly predominant in assemblages under moderate pH conditions, whereas Alphaproteobacteria, Euryarchaeota, Gammaproteobacteria and Nitrospira exhibited a strong adaptation to more acidic environments. Strikingly, such pH-dependent patterns could also be observed in a subsequent comprehensive analysis of the environmental distribution of acidophilic microorganisms based on 16S rRNA gene sequences previously retrieved from globally distributed AMD and associated environments, regardless of the long-distance isolation and the distinct substrate types. Collectively, our results suggest that microbial diversity patterns are better predicted by contemporary environmental variation rather than geographical distance in extreme AMD systems.
acid mine drainage; biogeography; contemporary environmental variation; geographical distance; microbial diversity; pyrosequencing
Chronic kidney disease (CKD) is a major cause of death and morbidity in Australia and worldwide. DNA vaccination has been used for targeting foreign antigens to induce immune responses and prevent autoimmune disease, viral infection and cancer. However, the use of DNA vaccination has been restricted by a limited ability to induce strong immune responses, especially against self-antigens which are limited by mechanisms of self-tolerance. Furthermore, there have been few studies on the potential of DNA vaccination in chronic inflammatory diseases, including CKD. We have established strategies of DNA vaccination targeting specific self-antigens in the immune system including co-stimulatory pathways, T cell receptors and chemokine molecules, which have been effective in protecting against the development of CKD in a variety of animal models. In particular, we find that the efficacy of DNA vaccination is improved by dendritic cell (DC) targeting and can protect against animal models of autoimmune nephritis mimicking human membranous nephropathy. In this review, we summarize several approaches that have been tested to improve the efficacy of DNA vaccination in CKD models, including enhanced DNA vaccine delivery methods, DNA vaccine modifications and new molecular targets for DNA vaccination. Finally, we discuss the specific application of DNA vaccination for preventing and treating CKD.
DNA vaccination; dendritic cell; DEC205; CD40; cytokine; costimulatory molecular; active Heymann nephritis (HN); adriamycin nephropathy (AN)
While breast milk has unique health advantages for infants, the mechanisms by which it regulates the physiology of newborns are incompletely understood. miRNAs have been described as functioning transcellularly, and have been previously isolated in cell-free and exosomal form from bodily liquids (serum, saliva, urine) and tissues, including mammary tissue. We hypothesized that breast milk in general, and milk fat globules in particular, contain significant numbers of known and limited novel miRNA species detectable with massively parallel sequencing. Extracted RNA from lactating mothers before and following short-term treatment with recombinant human growth hormone (rhGH) was smRNA-enriched. smRNA-Seq was performed to generate 124,110,646 36-nt reads. Of these, 31,102,927 (25%) exactly matched known human miRNAs; with relaxing of stringency, 74,716,151 (60%) matched known miRNAs including 308 of the 1018 (29%) mature miRNAs (miRBase 16.0). These miRNAs are predicted to target 9074 genes; the 10 most abundant of these predicted to target 2691 genes with enrichment for transcriptional regulation of metabolic and immune responses. We identified 21 putative novel miRNAs, of which 12 were confirmed in a large validation set that included cohorts of lactating women consuming enriched diets. Of particular interest, we observed that expression of several novel miRNAs were altered by the perturbed maternal diet, notably following a high-fat intake (p<0.05). Our findings suggest that known and novel miRNAs are enriched in breast milk fat globules, and expression of several novel miRNA species is regulated by maternal diet. Based on robust pathway mapping, our data supports the notion that these maternally secreted miRNAs (stable in the milk fat globules) play a regulatory role in the infant and account in part for the health benefits of breast milk. We further speculate that regulation of these miRNA by a high fat maternal diet enables modulation of fetal metabolism to accommodate significant dietary challenges.
Bub1 is a critical component of the spindle assembly checkpoint (SAC) and closely linked to cell proliferation and differentiation. We previously found that spontaneous abortion embryos contained a low level of Bub1 protein but normal mRNA level, while the knockdown of Bub1 leads to abnormal numerical chromosomes in embryonic cells. Here, we investigated the mechanism through which governs the post-transcriptional regulation of Bub1 protein expression level. We first conducted bioinformatics analysis and identified eight putative miRNAs that may target Bub1. Luciferase reporter assay confirmed that miR-450a-3p can directly regulate Bub1 by binding to the 3′-untranslated region of Bub1 mRNA. We found that the overexpression of miR-450a-3p in mouse embryonic fibroblast (MEF) cells down-regulated Bub1 protein level, repressed cell proliferation, increased apoptosis and restricted most cells in G1 phase of the cell cycle. Furthermore, when the fertilized eggs were microinjected with miR-450a-3p mimics, the cleavage of zygotes was effectively suppressed. Our results strongly suggest that an abnormally decreased Bub1 level regulated by miRNAs may be implicated in the pathogenesis of spontaneous miscarriage. Therefore, the blockade of miR-450a-3p may be explored as a novel therapeutic strategy for preventing spontaneous miscarriages.
Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14–1.54) and lung cancer (OR = 1.57; 95% CI = 1.31–1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13–1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.
Understanding the microanatomy of the facial nerve is vital to functional restoration of facial nerve injury. This study aimed to locate the spatial orientation of five branches in the extratemporal trunk of the rat facial nerve (ETFN). Fifteen adult Sprague-Dawley albino rats were divided randomly into five groups corresponding to the five facial nerves. Fluoro-Gold™ (FG) was applied to one branch in all three rats in each group. The trunk of the facial nerve was cut at three points for fluorescence detection. Staining results showed that each branch of the facial motor nerve had a topographical orientation in the distal part of the ETFN. The temporal branch was located in the medial and acroscopic quadrant of the nerve trunk. The zygomatic branch was located in the lateral and acroscopic quadrant. The buccal branch occupied the upper half of the nerve trunk, whereas the mandibular branch occupied the lower half. The cervical branch presented a square-shaped distribution in the lateral nerve trunk. In the middle part of the ETFN, the topographical orientation remained clear, but the FG-labeled zone was extended to some extent. In the stylomastoid foramen region, all branches diffused, thereby blurring the orientation. In conclusion, each branch of the facial motor nerve had a topographical orientation and distribution in the crotch and middle part of the ETFN, but the branches diffused near the stylomastoid foramen.
facial nerve; anatomy; nerve fibers; temporal bone; Fluoro-Gold; rats
Breeding for strong red skin color is an important objective of the pear breeding program. There are few reports of proteome research in green skin pear and its red skin bud mutation. The manuscript at hand is one of the first studies dealing with 2D-PAGE-based analysis of pear fruits and leaves, establishing a suitable sample preparation and testing different 2D-PAGE protocols. Therefore, it may grant a basis for further studies on the pear proteome being the studies main goal. A proteomic analysis was conducted on leaves and fruits of ‘Zaosu’ pear (Pyrus bretschneideri Rehd.) and its red skin bud mutation in order to reveal their genetic differences in the protein level.
In the present study, the optimized two-dimensional (2-D) gel electrophoresis system of pear leaf and fruit was set up, and applied to analyze the leaves and fruit protein. The interesting peptide fragments were determined using 4800 Plus MALDI TOF/TOFTM Analyzer mass spectrometer, and the sequence obtained was blasted in NCBInr to identify the differentially-expressed protein. In the 1.5-fold differently-expressed proteins between ‘Zaosu’ pear and its mutant, 10 out of 35 proteins in fruit and 12 out of 24 ones in leaves were identified successfully. Among the 22 identified proteins, 7 protein spots were related to photosynthesis and energy metabolism; 4 were associated with environmental stress; 4 with disease defense; 2 with amino acid metabolism; 2 with cytoskeleton; 1 with antioxidant function; 1 with calcium metabolism; and 1 with unknown function. Moreover, related physiological index, such as chlorophyll content, Rubisco content and polyphone oxidase activity, were different between ‘Zaosu’ pear and its mutant.
A 2-D gel electrophoresis system of pear leaves and fruits was established, which was suitable for the analysis of proteome comparison. To the best of our knowledge, we have performed the first analysis of the proteomic changes in leaves and fruits of ‘Zaosu’ pear and its red skin bud mutation. Our study provides important information on the use of proteomic methods for studying protein regulation of ‘Zaosu’ pear and its red skin bud mutation.
Pear; Red skin bud mutation; Plant proteomics; MALDI TOF/TOF-MS
Genome sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2,951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in non-essential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes, and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.
To evaluate the short-term effect of fangchinoline, an antiinflammatory drug widely used in Asia, on root resorption that is associated with orthodontic tooth movement.
Twenty-four Wistar rats were randomly divided into 6 groups. Mesial forces of 0, 50, or 100 g were applied to the maxillary first molar of the rats in each group for 14 days by activating nickel-titanium closed-coil springs. One-half of the rats receiving each of these treatments also received injections of 200 µL fangchinoline every 2 days. Finally, movement of the maxillary first molars was measured using digitized radiographs. The molars were extracted and the surfaces of the root resorption craters were recorded using a scanning electron microscope. The distance the molars moved and resorptionarea ratio was measured, and results were analyzed using 2-way ANOVA tests.
There were no statistical differences in the distances the first molars moved under 50 or 100 g force, regardless of treatment with fangchinoline. However, the resorption area ratios were significantly smaller in those rats that were treated with both tension and fangchinoline than in those rats treated by tension alone.
Fangchinoline reduced the resorption area ratio in rats and is therefore an important means of alleviating root resorption.
SEM; Root resorption; Tooth movement
Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
Partial hepatectomy (PH) triggers hepatocyte proliferation–mediated liver repair and is widely used to study the mechanisms governing liver regeneration in mice. However, the dynamics of the hepatocyte proliferative response to PH remain unclear. We found that PH-induced mouse liver regrowth was driven by four consecutive waves of hepatocyte replication. The first wave exhibited the highest magnitude followed by two moderate waves and one minor wave. Underlying this continuous hepatocyte replication was persistent activation of cell cycle components throughout the period of liver regeneration. Hepatocyte mitotic activity in the first three proliferative cycles showed a circadian rhythm manifested by three corresponding mitosis peaks, which were always observed at Zeitgeber time 0. The Bmal1-Clock/Wee1/Cdc2 pathway has been proposed by others to govern the circadian rhythm of hepatocyte mitosis during liver regeneration. However, we did not observe the correlations in the expression or phosphorylation of these proteins in regenerating livers. Notably, Bmal1 protein displayed frequent changes in hepatic distribution and cellular localization as the liver regrowth progressed. Further, three waves of hepatic fat accumulation occurred during hepatic regeneration. The first started before and lasted through the first round of hepatocyte proliferation, whereas the second and third occurred concomitantly with the second and third mitotic peaks, respectively.
PH-induced liver regeneration consists of four continuous waves of hepatocyte proliferation coupled with three waves of hepatic fat accumulation. Bmal1, Wee1, and Cdc2 may not form a pathway regulating the circadian rhythm of hepatocyte mitosis during liver regeneration.
Eukaryotic proteasome consists of a core particle (CP), which degrades unfolded protein, and a regulatory particle (RP), which is responsible for recognition, ATP-dependent unfolding and translocation of polyubiquitinated substrate protein. In the archaea Methanocaldococcus jannaschii, the RP is a homohexameric complex of proteasome-activating nucleotidase (PAN). Here we report the crystal structures of essential elements of the archaeal proteasome: the CP, the ATPase domain of PAN, and a distal subcomplex that is likely the first to encounter substrate. The distal subcomplex contains a coiled-coil segment and an OB-fold domain, both of which appear to be conserved in the eukaryotic proteasome. The OB domains of PAN form a hexameric ring with a 13-Å pore, which likely constitutes the outermost constriction of the substrate translocation channel. These studies reveal structural codes and architecture of the complete proteasome, identify potential substrate-binding sites, and uncover unexpected asymmetry in the RP of archaea and eukaryotes.
Monocytes utilise a variety of chemokines to traffic to atherosclerotic plaques. CX3C chemokine ligand 1 (CX3CL1 & Fractalkine) and its receptor CX3CR1 and monocyte chemoattractant protein 1 (CCL2) have been identified as chemokines/receptors that have an important role in the migration and recruitment of monocytes during the pathogenesis of several inflammatory diseases including atherosclerosis. DNA vectors containing single chain variable region fragment (scFv) for DC-targeted receptor DEC205 were cloned with mouse CX3CR1 and CCL2 genes respectively, and vaccinated into C57/BL6 mice weekly for 3 weeks. Induced anti-CX3CR1 and anti-CCL2 in vaccinated mice was examined by ELISA and Western Blot analysis, while the cellular response was examined by ELISPOT. The inhibition of chemotaxis of J774 macrophages to Py-4-1 endothelial cells was examined by in vitro transwell migration assay using serum collected from vaccinated mice. All vaccinated mice generated anti-CX3CR1 and anti-CCL2 Ab and cellular response by 8 weeks after DNA vaccination. Macrophage migration towards TNF-α activated endothelial cells was significantly inhibited by serum containing both anti-CX3CR1 or anti-CCL2 Ab from vaccinated mice. These results demonstrate that DC-targeting of DNA vaccines to self-antigens generates functional immune responses which can inhibit specific key chemotactic targets. This suggests a potential therapeutic role for chemokine/receptor DNA vaccination in atherosclerosis, where chemotaxis has a pivotal role in the inflammatory process.
DNA Vaccination; DEC205; macrophage migration; chemokine; CX3CR1; CCL2
A mesoscopic nitrogen-doped TiO2 sphere has been developed for a quasi-solid-state dye-sensitized solar cell [DSSC]. Compared with the undoped TiO2 sphere, the quasi-solid-state DSSC based on the nitrogen-doped TiO2 sphere shows more excellent photovoltaic performance. The photoelectrochemistry of electrodes based on nitrogen-doped and undoped TiO2 spheres was characterized with Mott-Schottky analysis, intensity modulated photocurrent spectroscopy, and electrochemical impedance spectroscopy, which indicated that both the quasi-Fermi level and the charge transport of the photoelectrode were improved after being doped with nitrogen. As a result, a photoelectric conversion efficiency of 6.01% was obtained for the quasi-solid-state DSSC.
We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other.
Electronic supplementary material
The online version of this article (doi:10.1007/s00439-011-1111-9) contains supplementary material, which is available to authorized users.
The metabolic pathways utilized by higher eukaryotic organisms to deal with potentially carcinogenic xenobiotic compounds from tobacco smoke have been well characterized. Carcinogenic compounds such as polycyclic aromatic hydrocarbons are metabolized sequentially in two-phases: in phase I CYP1A1 catalyzes conversion into harmful hydrophilic DNA adducts, while in phase II GSTT1 enables excretion via conjugation into polar electrophiles. In an effort to understand susceptibility to in utero tobacco exposure, we previously characterized known metabolic functional polymorphisms and demonstrated that while deletion of fetal GSTT1 significantly modified birth weight in smokers, no polymorphism fully accounted for fetal growth restriction. Since smoking upregulates CYP1A1 expression, we hypothesized that non-allelic (epigenetic) dysregulation of placental CYP1A1 expression via alterations in DNA methylation (meCpG) may further modify fetal growth. In the present manuscript, we compared placental expression of multiple CYP family members among gravidae, and observed significantly increased CYP1A1 expression among smokers relative to controls (4.4-fold, p<0.05). To fully characterize CYP1A1 meCpG status, bisulfite modification and sequencing of the entire proximal 1 kb promoter (containing 59 CpG sites) was performed. CpG sites immediately proximal to the 5′-XRE transcription factor binding element were significantly hypomethylated among smokers (55.6% vs 45.9% meCpG, p=0.027), a finding which uniquely correlated with placental gene expression (r=0.737, p=0.007). Thus in utero tobacco exposure significantly increases placental CYP1A1 expression in association with differential methylation at a critical XRE element.
Background: Epidemiologic evidence for a causative association between black carbon (BC) and health outcomes is limited.
Objectives: We estimated associations and exposure–response relationships between acute respiratory inflammation in schoolchildren and concentrations of BC and particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) in ambient air before and during the air pollution intervention for the 2008 Beijing Olympics.
Methods: We measured exhaled nitric oxide (eNO) as an acute respiratory inflammation biomarker and hourly mean air pollutant concentrations to estimate BC and PM2.5 exposure. We used 1,581 valid observations of 36 subjects over five visits in 2 years to estimate associations of eNO with BC and PM2.5 according to generalized estimating equations with polynomial distributed-lag models, controlling for body mass index, asthma, temperature, and relative humidity. We also assessed the relative importance of BC and PM2.5 with two-pollutant models.
Results: Air pollution concentrations and eNO were clearly lower during the 2008 Olympics. BC and PM2.5 concentrations averaged over 0–24 hr were strongly associated with eNO, which increased by 16.6% [95% confidence interval (CI), 14.1–19.2%] and 18.7% (95% CI, 15.0–22.5%) per interquartile range (IQR) increase in BC (4.0 μg/m3) and PM2.5 (149 μg/m3), respectively. In the two-pollutant model, estimated effects of BC were robust, but associations between PM2.5 and eNO decreased with adjustment for BC. We found that eNO was associated with IQR increases in hourly BC concentrations up to 10 hr after exposure, consistent with effects primarily in the first hours after exposure.
Conclusions: Recent exposure to BC was associated with acute respiratory inflammation in schoolchildren in Beijing. Lower air pollution levels during the 2008 Olympics also were associated with reduced eNO.
air pollution intervention; black carbon; nitric oxide; PM2.5; respiratory inflammation; schoolchildren
To manage a patient's blood pressure and recovery, and to reduce unnecessary hospital visits after heart surgery, we developed and established a telecare service.
We established and test-operated the system that enabled biometric data to be measured and monitored at home, and directed connections to the video consultation with monitoring personnel and medical staff when abnormal symptoms were detected.
As a result of using the telecare service with patients discharged from the hospital after undergoing heart surgery, the patients were mostly satisfied with the service and use of the equipment, and some patients wanted to actually receive the service continuously along with a device which could be more easily used.
Telecare services are greatly needed for patients discharged after heart surgery for a certain period of time. A model should be developed which provides devices necessary for each disease in package form and customizes the content and services in one package.
Personal Health Services; Telemedicine; Heart Diseases; Self-Care; Remote Consultation
The link between concentrations of particulate matter (PM) and respiratory morbidity has been investigated in numerous studies.
The aim of this study was to analyze the role of different particle size fractions with respect to respiratory health in Beijing, China.
Data on particle size distributions from 3 nm to 1 μm; PM10 (PM ≤ 10 μm), nitrogen dioxide (NO2), and sulfur dioxide concentrations; and meteorologic variables were collected daily from March 2004 to December 2006. Concurrently, daily counts of emergency room visits (ERV) for respiratory diseases were obtained from the Peking University Third Hospital. We estimated pollutant effects in single- and two-pollutant generalized additive models, controlling for meteorologic and other time-varying covariates. Time-delayed associations were estimated using polynomial distributed lag, cumulative effects, and single lag models.
Associations of respiratory ERV with NO2 concentrations and 100–1,000 nm particle number or surface area concentrations were of similar magnitude—that is, approximately 5% increase in respiratory ERV with an interquartile range increase in air pollution concentration. In general, particles < 50 nm were not positively associated with ERV, whereas particles 50–100 nm were adversely associated with respiratory ERV, both being fractions of ultrafine particles. Effect estimates from two-pollutant models were most consistent for NO2.
Present levels of air pollution in Beijing were adversely associated with respiratory ERV. NO2 concentrations seemed to be a better surrogate for evaluating overall respiratory health effects of ambient air pollution than PM10 or particle number concentrations in Beijing.
emergency room visits; particle number concentration; particle surface area concentration; particulate matter; short-term effects; time-series analyses; ultrafine particles
In the title cobalt(II) compound, [Co(C12H21N2Si)Cl(C6H16N2)], the ethane-1,2-diamine donor molecule coordinates the metal atom in an N,N′-chelating mode, with Co—N distances of 2.136 (2) and 2.140 (3) Å. An anilide ligand connects to the CoII atom with a σ–bond, the Co—Nanilide distance being 1.931 (2) Å. The four-coordinate CoII atom demonstrates a slightly distorted tetrahedral geometry.
Bioartificial kidneys (BAKs) combine a conventional hemofilter in series with a bioreactor unit containing renal epithelial cells. The epithelial cells derived from the renal tubule should provide transport, metabolic, endocrinologic and immunomodulatory functions. Currently, primary human renal proximal tubule cells are most relevant for clinical applications. However, the use of human primary cells is associated with many obstacles, and the development of alternatives and an unlimited cell source is one of the most urgent challenges. BAKs have been applied in Phase I/II and Phase II clinical trials for the treatment of critically ill patients with acute renal failure. Significant effects on cytokine concentrations and long-term survival were observed. A subsequent Phase IIb clinical trial was discontinued after an interim analysis, and these results showed that further intense research on BAK-based therapies for acute renal failure was required. Development of BAK-based therapies for the treatment of patients suffering from end-stage renal disease is even more challenging, and related problems and research approaches are discussed herein, along with the development of mobile, portable, wearable and implantable devices.