Improvements in Air Quality and Health Outcomes Among California Medicaid Enrollees Due to Goods Movement Actions.

INTRODUCTION: In 2006, the California Air Resources Board (CARB) and local air quality management districts implemented an Emission Reduction Plan for Ports and Goods Movement program (referred to hereinafter as GM policy actions) (CARB 2006). The GM policy actions comprise approximately 200 actions with an estimated investment value of $6 to $10 billion. These actions targeted the major sources and polluters related to goods movements, such as highways; ports and railyard trucks; ship fuel and shore power; cargo equipment; and locomotives. These actions aimed to reduce total statewide domestic GM emissions to 2001 levels or lower by the year 2010; to reduce the statewide diesel particulate matter (DPM) health risk from GM by 85% by the year 2020; and to reduce the nitrogen oxides (NOx) emissions from international GM in the South Coast Air Basin by 30% from projected 2015 levels and 50% from projected 2020 levels. The years 2006 and 2007 marked an important milestone in starting to regulate GM polluters and adopting stricter standards for traffic-related air pollution.This project aimed to examine the impact of the GM policy actions on reductions in ambient air pollution and subsequent improvements in health outcomes of Medi-Cal fee-for-service (FFS) beneficiaries with chronic conditions in 10 counties in California. Specifically, we examined whether the GM policy actions reduced air pollution near GMC corridors more than in control areas. We subsequently assessed whether there were greater decreases in emergency room (ER) visits and hospitalizations for enrollees with chronic conditions who lived in the GM corridors (GMCs) than for those who lived in other areas. METHODS: The study used a quasi-experimental design. We defined areas within 500 m of truck-permitted freeways and ports as GMCs. We further defined non-goods movement corridors (NGMCs) as locations within 500 m of truck-prohibited freeways or 300 m of a connecting roadway, and areas out of GMCs and NGMCs as controls (CTRLs). We defined years 2004-2007 as the pre-policy period and years 2008-2010 as the post-policy period. We developed linear mixed-effects land use regression models and created annual air pollution surfaces for nitrogen dioxide (NO2), fine particulate matter (PM2.5), and ozone (O3) across California for years 2004-2010 at a spatial resolution of 30 m, then assigned them to enrollees' home addresses.We used a retrospective cohort of 23,000 California Medicaid (Medi-Cal) FFS adult beneficiaries living in 10 California counties with six years of data (September 1, 2004, to August 31, 2010). Cohort beneficiaries had at least one of four chronic conditions, including asthma, chronic obstructive pulmonary disease (COPD), diabetes, and heart disease.We used a difference-in-differences (DiD) model to assess whether air pollutant concentration and health care utilization (ER visits and hospitalizations) for cohort beneficiaries declined more for those living in intervention corridors (GMCs, NGMCs) than those living in CTRLs. All the models controlled for age, sex, language spoken, race/ethnicity, number of comorbidities in baseline years, county, time-varying health indicator variables, and several neighborhood variables.To facilitate interpretation, we calculated the DiD estimates in each of the three years after the policy intervention. The DiD was used to assess the causal impact of regulatory policy on reductions of air pollution, as well as for the improvements in health outcomes.We explored whether improvements in health outcomes were due to the air pollution reduction by using a multi- level mediation model, in which the effect of GM actions on health outcomes was mediated through the effect of actual air pollution reductions in the post-policy years. We used the Generalized Structural Equation Models for the estimation and combined the effects of NO2 and PM2.5 in the model. To further verify the causal inferences of the GM actions on reductions of exposures and improvements in health outcomes, we performed sensitivity analyses with propensity score weighting. RESULTS: We observed statistically significant reductions in pollutant NO2 and PM2.5 concentrations for enrollees in all 10 counties. The enrollees in GMCs experienced greater reductions in NO2 and PM2.5 from the pre- to the post-policy periods than those in CTRLs. Greater reductions were also observed among beneficiaries living in NGMCs versus those in CTRLs, but those reductions were smaller than among beneficiaries living in GMCs. For O3 concentrations, an opposite trend was observed.Furthermore, we observed significantly greater reductions in ER visits for patients with asthma and COPD living in GMCs than those in CTRLS in the post-policy years. For example, we saw in the DiD modeling results there were 170 fewer ER visits for 1,000 beneficiaries with asthma per year in GMCs if the regionwide trend in the CTRL group was considered not related to the GM policy. Similarly, among the beneficiaries with COPD, there were 180 fewer ER visits per 1,000 patients estimated in the GMCs for the third year after the implementation of the policy.We also observed greater reductions in ER visits among those with asthma, when comparing NGMCs with CTRLs, but reductions were smaller than comparisons between GMCs and CTRLs. The ER visits for those with COPD, diabetes, and the total sample in NGMCs also had downward trends in the post-policy year in comparison with those in CTRLs but the differences were not statistically significant; similar phenomena were also observed for the ER visits among those with diabetes and heart diseases and in the total sample when GMCs versus CTRLs and GMCs versus NGMCs were compared. Although hospitalizations also decreased more in GMCs than in NGMCs and more in NGMCs than in CTRLs in the post-policy period, results were not statistically significant.Using the mediation models, we observed 0.129 more reductions in the expected number of ER visits among individuals with asthma for a composite reduction in one unit NO2 and one unit PM2.5 (DiD = -0.129, P < 0.05) from the pre-policy years to the post-policy years. The reductions in NO2 and PM2.5 due to policy change estimated by the mediation model are essentially the same as shown in the respective DiD models. Mediation analyses suggested that the effects of GM policy interventions on health improvements were largely due to exposure reductions. Finally, sensitivity analyses with propensity scores produced similar DiD results. CONCLUSIONS: This project has produced empirical evidence that air pollution control actions reduced pollution exposures among disadvantaged and susceptible populations. More importantly, our findings suggest that the reductions in air pollution led to health outcome improvements among low-income people with chronic conditions. Our investigation also contributed to scientific methods for assessing the health effects of long-term, large-scale, and complex regulatory actions with routinely collected pollutants and medical claims data. Therefore, the results strongly support both short-term and long-term efforts to improve air quality for all members of society and future studies on the impact of air pollution control policies.

SNP-based susceptibility-resistance association and mRNA expression regulation analyses of tlr7 to grass carp Ctenopharyngodon idella reovirus.

Eleven single nucleotide polymorphisms (SNP) in Ctenopharyngodon idella toll-like receptor 7 (citlr7) gene, containing two in the 5'-flanking region, three within the single intron and six distributed in the coding sequence (CDS), were identified. A case-control study of 73 susceptible individuals and 67 resistant individuals was conducted to test the SNPs-based susceptibility-resistance association and mRNA expression of citlr7 to grass carp reovirus (GCRV), showing that both 820 A/G and 1726 A/G were significantly correlative sites in genotype (P < 0·05). Multifactor dimensionality reduction (MDR) analysis suggested the exertion of antiviral effects of 820 A/G might rely on SNPs interactions of citlr7 and C. idella toll-like receptor 8 (citlr8). Combining the mortality rate and citlr7 mRNA expression, it was suggested that 1726 GG-genotyped individuals might be more resistant than 1726 A/G genotyped individuals, indicating the selection on synonymous mutations in 1726 A/G might be susceptibility-resistance-type specific. In addition, haplotype analysis uncovered no significantly correlative haplotypes in citlr7. These findings may provide an in-depth insight for the further functional research of citlr7. The potential genetic markers identified may contribute to the molecular and transgenic breeding of C. idella.

[Correlation between job burnout and salivary cortisol concentration in employees].

OBJECTIVE: To investigate the correlation between job burnout and salivary cortisol concentration. METHODS: In September 2014, a cross-sectional survey was used to perform a questionnaire survey for 237 employees in a solar photovoltaic company. Meanwhile, saliva was collected through chewing with a tube for saliva collection, and enzyme-linked immunosorbent assay was used to measure salivary cortisol concentration. RESULTS: The salivary cortisol concentration showed no significant differences between employees with different ages, working years, educational backgrounds, and shifts(P>0.05). The salivary cortisol concentration was positively correlated with the scores of emotional exhaustion, depersonalization, and job burnout(r=0.182, 0.229, and 0.222, P<0.05). The employees with emotional exhaustion, depersonalization, and job burnout had significantly higher salivary cortisol concentrations than those without emotional exhaustion, depersonalization, and job burnout(80.22±13.34 µg/L vs 75.86±14.75 µg/L, t=2.029, P<0.05; 80.69±12.99 µg/L vs 75.27±14.89 µg/L, t=2.607, P<0.05; 80.06±12.63 µg/L vs 72.76±16.04 µg/L, t=3.248, P<0.05). The stepwise regression analysis showed that salivary cortisol concentration was mainly influenced by depersonalization. CONCLUSION: Job burnout is correlated with salivary cortisol concentration, and can be used as an objective assessment index for job burnout.

Identification and expression analysis of the sting gene, a sensor of viral DNA, in common carp Cyprinus carpio.

Stimulator of interferon gene (sting) was identified and characterized from common carp Cyprinus carpio. The sting messenger (m)RNA encoded a polypeptide of 402 amino acids with a calculated molecular mass of 46·184 kDa and an isoelectronic point of 6·08. The deduced protein of sting contained a signal peptide, three transmembrane motifs in the N-terminal region and four putative motifs (RXR) found in resident endoplasmic reticulum proteins. mRNA expression of sting was present in twelve investigated tissues, and was up-regulated by koi herpesvirus (KHV) in vivo and in vitro. The transcription of sting was altered by poly(I:C) and poly(dT:dA) stimulation in vitro. The findings suggested that sting is an inducible gene involved in innate immunity against DNA- and RNA-derived pathogens. To investigate defence mechanisms in C. carpio development, sting level in embryos, larvae and juvenile fish was monitored following KHV challenge. The sting message was negligible in embryos prior to hatching, but observed at higher transcriptional levels throughout larval and juvenile stages. Investigation showed the mRNA expression profiles of genes encoding for proteins promoting various functions in the interferon pathway, from pattern recognition receptors to antiviral genes, to be significantly induced in all examined organs by in vivo infection with KHV. Following KHV infection, the ifn message was significantly downregulated in spleen, head kidney, brain and hepatopancreas but notably up-regulated in gill, intestine and skin, suggesting that ifn induction might be related to the mucosal immune system and virus anti-ifn mechanisms. These results provided the basis for further research into the role and mechanisms of sting in fishes.

Identification and expression of the laboratory of genetics and physiology 2 gene in common carp Cyprinus carpio.

In this study, a laboratory of genetics and physiology 2 gene (lgp2) from common carp Cyprinus carpio was isolated and characterized. The full-length complementary (c)DNA of lgp2 was 3061 bp and encoded a polypeptide of 680 amino acids, with an estimated molecular mass of 77 341·2 Da and a predicted isoelectric point of 6·53. The predicted protein included four main overlapping structural domains: a conserved restriction domain of bacterial type III restriction enzyme, a DEAD-DEAH box helicase domain, a helicase super family C-terminal domain and a regulatory domain. Real-time quantitative polymerase chain reaction (PCR) showed widespread expression of lgp2, mitochondrial antiviral signalling protein (mavs) and interferon transcription factor 3 (irf3) in tissues of nine organs. lgp2, mavs and irf3 expression levels were significantly induced in all examined organs by infection with koi herpesvirus (KHV). lgp2, mavs and irf3 messenger (m)RNA levels were significantly up-regulated in vivo after KHV infection, and lgp2 transcripts were also significantly enhanced in vitro after stimulation with synthetic, double-stranded RNA polyinosinic polycytidylic [poly(I:C)]. These findings suggest that lgp2 is an inducible protein involved in the innate immune defence against KHV in C. carpio. These results provide the basis for further research into the role and mechanisms of lgp2 in fishes.

Total knee arthroplasty treatment of active tuberculosis of the knee: a review of 10 cases.

OBJECTIVE: To discuss the surgical methods of total knee arthroplasty (TKA) in the patients with active tuberculosis of the knee and find out its curative effect after TKA. PATIENTS AND METHODS: We analyzed 10 patients with active tuberculosis of the knee who received TKA in our department from March 2006 to March 2010, whose ages were from 22 to 64 years old (average age was 40.6 ± 1 years). The following parameters were measured in the pre- and post-operation periods: HSS score, range of motion (ROM). From x-ray to find out post-operate curative effect of TKA. RESULTS: All cases had pain and elevated ESR. Deep vein thrombosis (DVT) and nerve damage were not found in these cases. There were 4 cases that had sinuses on the skin: the skin healed before the operation took place. Pre-operation HSS average scores were 25.0 ± 2. All patients received TKA by the para-patellar medial approach. Eight cases were followed-up for 6-28 months; the average follow-up period was 14 ± 0.5 months. Post-operation we took an HSS score and X-rays to find out its curative effect after TKA operation. There were also no patients with dislocation, aseptic loosening or fracture of prosthesis, although 1 case had recurrence. Post-operation's HSS average scores were 86.75 ± 5.45. The average ROM was improved to 95 ± 5°. CONCLUSIONS: Recent clinical results indicate that TKA is effective to treat the patients with active tuberculosis of the knee joint. TKA can significantly improve the function of the joint and relieve pain, improving patients' living conditions.

A distance-decay variable selection strategy for land use regression modeling of ambient air pollution exposures.

Land use regression (LUR) has emerged as an effective and economical means of estimating air pollution exposures for epidemiological studies. To date, no systematic method has been developed for optimizing the variable selection process. Traditionally, a limited number of buffer distances assumed having the highest correlations with measured pollutant concentrations are used in the manual stepwise selection process or a model transferred from another urban area. In this paper we propose a novel and systematic way of modeling long-term average air pollutant concentrations through "A Distance Decay REgression Selection Strategy" (ADDRESS). The selection process includes multiple steps and, at each step, a full spectrum of correlation coefficients and buffer distance decay curves are used to select a spatial covariate of the highest correlation (compared to other variables) at its optimized buffer distance. At the first step, the series of distance decay curves is constructed using the measured concentrations against the chosen spatial covariates. A variable with the highest correlation to pollutant levels at its optimized buffer distance is chosen as the first predictor of the LUR model from all the distance decay curves. Starting from the second step, the prediction residuals are used to construct new series of distance decay curves and the variable of the highest correlation at its optimized buffer distance is chosen to be added to the model. This process continues until a variable being added does not contribute significantly (p>0.10) to the model performance. The distance decay curve yields a visualization of change and trend of correlation between the spatial covariates and air pollution concentrations or their prediction residuals, providing a transparent and efficient means of selecting optimized buffer distances. Empirical comparisons suggested that the ADDRESS method produced better results than a manual stepwise selection process of limited buffer distances. The method also enables researchers to understand the likely scale of variables that influence pollution levels, which has potentially important ramifications for planning and epidemiological studies.

Purification, kinetics and inhibition by antimonials of recombinant phosphofructokinase from Schistosoma mansoni.

We reported before on the cloning of a cDNA encoding S. mansoni PFK. In the present investigation we established optimal conditions for expression of the enzyme in insect cells with high yield. The recombinant PFK was purified to homogeneity. Kinetic properties of the pure enzyme were studied with respect to its two substrates, Fru-6-P and ATP, and were compared with properties of mammalian PFK. ATP inhibited the parasite enzyme only at concentrations higher than those which inhibited mammalian muscle PFK. Saturation curves for Fru-6-P showed typical cooperative kinetics. AMP, cAMP and Fru-2,6-bisP activated the enzyme causing reduced apparent Km for Fru-6-P and an increase in maximal activity. Both ATP inhibition and cooperative kinetics for Fru-6-P occur at both pH 6.9 and 8.2. This is a distinct difference from the mammalian enzyme which shows these kinetic properties only at neutral or slightly acidic pH, but not at an alkaline pH. Recombinant PFK is more sensitive to inhibition by the trivalent antimonials, antimony potassium tartrate and Stibophen, than is the mammalian heart muscle enzyme. The inhibition is at least partially antagonized by the sulfhydryl protective reagent, dithiothreitol.

The mouse inhibin alpha-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice.

Testicular tumorigenesis was observed in transgenic mice expressing the 6-kb mouse inhibin alpha-subunit promoter/Simian virus 40 T-antigen (SV40 Tag) fusion gene. The tumors were confined to Leydig cells using immunohistochemistry with anti-Tag antibody, specific binding of biotinylated hCG and histochemistry for 3 beta-hydroxysteroid dehydrogenase. Leydig cell hyperplasia and presence of Tag protein in the testicular interstitial tissue were already evident at 5 and 6.5 days of age, respectively. An immortalized cell line, BLT-1, was established from one testicular tumor. These cells expressed the LH receptor and P450scc mRNAs, and displayed LH-responsive cAMP and progesterone production, and low testosterone production. The cells also specifically bound 125I-labeled recombinant human LH with high affinity (36000 binding sites/cell), and the binding was regulated by 8Br-cAMP and hCG. This gonadal tumor model is valuable for further studies on endocrine functions of Leydig cells and their tumorigenesis in vivo and in vitro.

Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines.

To establish in vivo gonadal tumor models and permanent lines of gonadal somatic cells we produced transgenic (TG) mice expressing the Simian virus (SV) 40 T-antigens (T-ag), driven by 6 or 2.1 kilobase fragments of the mouse inhibin alpha-subunit promoter. Hitherto, altogether 44 TG mice, one of which carried the shorter transgene, have produced gonadal tumors. Two founder females expressing the longer transgene, KK1 and KK3, and three established TG mouse lines were studied in detail. Penetrance of the phenotype in IT6-M and IT6-F mouse lines was 100% (tumors/TG: IT6-M 22/22, IT6-F 14/14). The T-ag mRNA was strongly expressed in the gonads, adrenal glands, pituitary, and brain. The KK-1 and KK-3 ovarian tumor cells immunostained with anti-SV40 large-T antibody. The KK-1 cells possessed high-affinity LH receptors [equilibrium association constant (Ka = 7.8 x 10(10) liters/mol] and responded to human CG by elevated cAMP and progesterone production. Also FSH slightly stimulated their cAMP and estradiol production (P < 0.01). These cells expressed cytochrome P450arom and inhibin alpha mRNA, but not cytochrome P450c17 alpha. In conclusion, the KK-1 cells are immortalized luteinizing granulosa cells expressing endogenous gonadotropin receptors, steroidogenic enzymes, and inhibin alpha. These cells will be useful in studies on the molecular aspects of granulosa cell function. The present study indicates that the 6-kilobase fragment of the inhibin alpha promoter described in this article contains the elements directing tissue-specific expression in vivo and is useful for targeted expression of other genes in the gonads.

Cloning and characterization of a cDNA encoding phosphofructokinase from Schistosoma mansoni.

Schistosoma mansoni, a human parasitic worm, depends on anaerobic glycolysis as the main source of energy. Phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11; PFK) limits the rate of glycolysis in these organisms and it has been found to be a target for some antischistosomal agents. A cDNA clone from this parasite has been isolated and characterized. The cDNA is 3046 base pairs long, contains an open reading frame of 2346 bp and codes for a deduced protein of 781 amino acids. The putative protein encoded by the clone has an exact match with the human muscle PFK of 58% and a 73% match when conserved amino acid substitutions are considered. ATP and Fructose-6-P sites have been identified by crystallographic data in the Escherichia coli and Bacillus stearothermophilus PFKs. There is excellent homology between those PFKs and the schistosome PFK at those sites. The PFK-coding cDNA was expressed in insect cells and was shown to be enzymatically active. Western blot analysis of the recombinant protein in cell extracts gave a positive band with the expected molecular weight of 86 kDa.

Luminescence luteinizing hormone/choriogonadotropin (LH/CG) bioassay: measurement of serum bioactive LH/CG during early pregnancy in human and macaque.

Because of the microheterogeneities of gonadotropins, measurement of immunoreactivity of these glycoproteins does not necessarily reflect changes in their bioactivity. In addition, LH bioactivities in human samples analyzed by a rodent LH bioassay have been discordant with findings based on human granulosa-luteal cells. We have isolated a human LH/choriogonadotropin (CG) receptor cDNA and expressed the recombinant protein. Using 293 cells permanently transfected with the human LH receptor cDNA and a luciferase reporter gene driven by a cAMP-dependent promoter, we have developed a luminescence LH/CG bioassay. After cells were treated with human LH or CG for 20 h, luciferase activity was measured through use of a luminometer. Luciferase activity in the cells was increased in a dose-dependent manner. In contrast, treatment with FSH, thyroid-stimulating hormone, prolactin, growth hormone, adrenocorticotropin, insulin, prostaglandins, and several neurotransmitters had no effect. Because treatment with basic fibroblast growth factor (bFGF) caused significant increases in basal luciferase activity, a fixed amount of bFGF was included in all reactions. Incubation with 0.1 to 30 microliters serum from women during different physiological states stimulated the luciferase activity in parallel with the hCG standard curve. In 4 conception cycles, bioactive LH/hCG levels began to increase 2 wk after the midcycle LH surge, followed by a logarithmic increase from 22 days on. Due to the lack of a homologous RIA for measuring CG levels in monkeys, we analyzed serum bioactive monkey CG (mCG) in macaque during early pregnancy. Bioactive mCG was detected about 12 days after the midcycle LH surge and fertile mating and persisted until Days 21-23, followed by a decline.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice.

The inhibins are alpha:beta heterodimeric growth factors that are members of the transforming growth factor-beta family. To understand the physiological roles of the inhibins in mammalian development and reproduction, a targeted deletion of the alpha-inhibin gene was generated by homologous recombination in mouse embryonic stem cells. Mice homozygous for the null allele (inhibin-deficient) initially develop normally but every mouse ultimately develops mixed or incompletely differentiated gonadal stromal tumours either unilaterally or bilaterally. Inhibin is thus a critical negative regulator of gonadal stromal cell proliferation and the first secreted protein identified to have tumour-suppressor activity.

Characterization of mouse inhibin alpha gene and its promoter.

Inhibin suppresses the pituitary secretion of FSH but not LH. The two forms of inhibin are composed of a common alpha subunit linked to either a beta A or a beta B subunit. The mouse inhibin alpha gene was isolated and shown to have two exons spanning a 1.7 Kb intron. The proximal 5' flanking region has neither TATA and CAAT boxes nor GC-rich area. Using the 5' flanking region of mouse inhibin alpha gene linked to luciferase gene, transfection of rat granulosa cells indicated that the first 165 bp of the promoter region is required for basal expression. The mouse inhibin alpha genomic clone should be useful for analysis of hormonal control of inhibin alpha transcription and the generation of mice with targeted deletion of this gene.

Activin stimulation of inhibin secretion and messenger RNA levels in cultured granulosa cells.

Recent reports suggest that activin (the dimer of inhibin beta subunits with FSH-releasing activity) has specific receptors on ovarian granulosa cells. The present study examined the effects of purified porcine activin on inhibin secretion and mRNA levels in granulosa cells obtained from immature, estrogen-treated rats. Cells were cultured for 48 h in culture media, or media containing FSH (10 ng/ml) and/or activin (30 ng/ml). Western blot analyses performed with affinity-purified antisera to inhibin alpha- and beta A-subunits revealed that treatment with either FSH or activin increased the secretion of inhibin alpha beta dimer (Mr 30,000), with a further increase after cotreatment. These results were confirmed by an inhibin alpha-subunit RIA, which revealed 7-, 14-, and 71-fold increases in the secretion of immunoreactive inhibin-alpha by activin, FSH, and activin plus FSH, respectively. TGF beta, a structural homolog of activin, also stimulated inhibin release, whereas follistatin was ineffective. Total RNA from cultured cells was hybridized with 32P-labeled inhibin alpha-subunit cRNA or beta-actin cDNA probes, and inhibin-alpha message levels were normalized with beta-actin mRNA levels. Northern blot analysis revealed that treatment with FSH and activin increased hybridization of a 1.5 kilobase (kb) message, corresponding to the inhibin alpha-subunit mRNA. Slot blot analyses indicated a 6- and 8-fold stimulation of inhibin alpha-subunit mRNA levels by FSH and activin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)