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BACKGROUND: Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. METHODS: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. RESULTS: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. CONCLUSIONS: Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

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Tropical peatlands are among the most carbon-dense ecosystems on Earth, and their water storage dynamics strongly control these carbon stocks. The hydrological functioning of tropical peatlands differs from that of northern peatlands, which has not yet been accounted for in global land surface models (LSMs). Here, we integrated tropical peat-specific hydrology modules into a global LSM for the first time, by utilizing the peatland-specific model structure adaptation (PEATCLSM) of the NASA Catchment Land Surface Model (CLSM). We developed literature-based parameter sets for natural (PEATCLSMTrop,Nat) and drained (PEATCLSMTrop,Drain) tropical peatlands. Simulations with PEATCLSMTrop,Nat were compared against those with the default CLSM version and the northern version of PEATCLSM (PEATCLSMNorth,Nat) with tropical vegetation input. All simulations were forced with global meteorological reanalysis input data for the major tropical peatland regions in Central and South America, the Congo Basin, and Southeast Asia. The evaluation against a unique and extensive data set of in situ water level and eddy covariance-derived evapotranspiration showed an overall improvement in bias and correlation compared to the default CLSM version. Over Southeast Asia, an additional simulation with PEATCLSMTrop,Drain was run to address the large fraction of drained tropical peatlands in this region. PEATCLSMTrop,Drain outperformed CLSM, PEATCLSMNorth,Nat, and PEATCLSMTrop,Nat over drained sites. Despite the overall improvements of PEATCLSMTrop,Nat over CLSM, there are strong differences in performance between the three study regions. We attribute these performance differences to regional differences in accuracy of meteorological forcing data, and differences in peatland hydrologic response that are not yet captured by our model.

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Chondrosarcomas are malignant bone tumors refractory to chemotherapy and radiation treatment; thus, novel therapeutic strategies are required. Proline­rich polypeptide 1 (PRP­1) has previously demonstrated antitumor properties in chondrosarcoma. To further investigate the role of PRP­1 in chondrosarcoma cells, its effects on cancer stem cell (CSC) populations were determined by analyzing aldehyde dehydrogenase (ALDH) activity, an established marker of CSCs, in association with regulation of the Wnt/ß­catenin signaling. A significant decrease in ALDHhigh CSCs was observed following treatment of chondrosarcoma JJ012 cells with PRP­1. For RT2 profiler PCR array analysis of Wnt/ß­catenin signaling genes, cells were sorted into: i) Bulk JJ012 cells; ii) ALDHhigh cells sorted from untreated JJ012 cells (ALDHhigh­untreated); and iii) ALDHlow cells sorted from PRP­1­treated JJ012 cells (ALDHlow­PRP­1). The expression levels of Wnt/ß­catenin signaling genes were determined to be downregulated in the ALDHhigh­untreated cells and upregulated in ALDHlow­PRP­1 cells when compared to the bulk JJ012 cells. Additionally, two important oncogenes involved in this pathway, MMP7 and CCND2, were found to be downregulated in the ALDHlow­PRP­1 cells. Immunocytochemistry demonstrated the localization of ß­catenin in the nuclei of the PRP­1­treated cells. Western blotting indicated increased ß­catenin expression in the ALDHlow­PRP­1 cells compared with the bulk JJ012 cells. Analysis of the cytoplasmic and nuclear fractions of cells treated with increasing concentrations of PRP­1 and ß­catenin nuclear translocation inhibitor CGP57380, suggested the nuclear translocation of ß­catenin following PRP­1 treatment. In addition, treatment of JJ012 cells with a specific ALDH inhibitor, diethylaminobenzaldehyde, and PRP­1 resulted in a significant decrease in cytoplasmic ß­catenin protein expression. This indicated that ALDH inactivation may be associated with the nuclear translocation of ß­catenin. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway has been previously documented. The findings of the present study support the notion that Wnt/ß­catenin activation may serve a differential role in sarcomas, limiting tumor progression in association with decreased CSC activity.

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Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.

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AIMS: To evaluate throughput of seeded Legionella pneumophila bacteria in domestic point-of-use filters. METHODS AND RESULTS: The filters were challenged with tap water seeded with Leg. pneumophila. After multiple challenge events (4.25 x 10(11) CFU per filter), the levels of Legionella were lower in the effluent from the filter containing both copper and silver (mean 4.48 x 10(3) CFU ml(-1)) than in the effluent from the filter containing copper only (1.26 x 10(4) CFU ml(-1); P < 0.001). After a single challenge event of approx. 5 x 10(9) CFU L. pneumophila per filter, there was no significant difference between the levels of Legionella in the effluents from a carbon filter containing copper and a carbon filter with no metals (mean 6.87 x 10(2) and 6.89 x 10(2) CFU ml(-1), respectively; P = 0.985). CONCLUSIONS: Legionella was detected in filter effluent up to 6 weeks after being challenged, indicating that while filters may reduce the levels during an initial contamination event, the exposure is extended as the accumulated bacteria slough off over time. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has provided an understanding of the response of Legionella to the use of silver and copper in domestic point-of-use carbon filters.

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The purpose of this trial was to evaluate the feasibility of concurrent paclitaxel/cisplatin and conventional thoracic irradiation in locally advanced non-small cell lung cancer (NSCLC). Ambulatory patients with medically inoperable or unresectable stage II-III NSCLC, and performance status 0-2 were eligible. Patients were not excluded from this trial if they had lost more than 5% of their body weight during the preceding 3 months, and/or if they had small ipsilateral pleural effusion. The initial dose of paclitaxel/cisplatin was 110 and 50 mg/m(2), and was escalated through five dose levels. Four cycles of chemotherapy were planned; the first two cycles were given concurrently with radiotherapy (4 weeks apart), followed by two additional cycles (every 3 weeks). Conventional chest radiotherapy to a total dose of 60 Gy (2 Gy per day) was delivered in 6 weeks. Forty-three patients were enrolled of which 38 were evaluable for response. Dose-limiting toxicities were grade 4 neutropenia (43% of patients) and grade 3 esophagitis (26% of patients) during the chemoradiotherapy phase. Grade > or = 2 acute and late pulmonary toxicity occurred in 10 and 68% of the patients, respectively. In most patients, prompt symptomatic and radiologic improvement was observed with early steroid administration. The volume of lung receiving 15-30 Gy was correlated with late pulmonary toxicity. The overall response was 84% with ten complete and 22 partial responses. The median survival was 16.5 months (95% confidence interval, 9.5 to 25) for those patients evaluable for response. After a median follow-up of 70 months, 5 (13%) patients are alive without evidence of disease. The maximum tolerated dose (MTD) of paclitaxel and cisplatin with concurrent radiotherapy is at dose level 3 paclitaxel (135 mg/m(2)) and cisplatin (75 mg/m(2)). Toxicity, although significant, was manageable in the great majority of the patients. The activity observed with this regimen is particularly noteworthy when considering the advanced nature of these patients, and the fact that patients (N=18) with poor risk factors were included in the study.

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OBJECTIVE: To determine the safety and efficacy of 3 clinically relevant vaccines in patients with systemic lupus erythematosus (SLE). METHODS: We studied 73 consecutive SLE patients immunized with pneumococcal, tetanus toxoid (TT), and Haemophilus influenzae type B (HIB) vaccines. Patients were evaluated preimmunization and 12 weeks postimmunization for disease activity and immunization side effects. RESULTS: Eighty-four percent of the SLE patients developed a 4-fold titer increase in response to at least 1 vaccine, with 51% developing a 2-fold titer increase with all 3 vaccines. The majority of SLE patients developed protective levels of antibody to TT (90%) and HIB (88%). Although protective antibody levels could not be determined for pneumococcus, almost half of the patients (47%) developed a 4-fold antibody response. There was a trend toward a lower antibody response in patients with active disease treated with immunosuppressive therapy. Overall lupus disease activity was unaffected by immunization. CONCLUSION: Immunization is safe in SLE patients, with the overwhelming majority developing protective antibody levels. Therefore, SLE patients should receive immunizations according to the recommendations of the Centers for Disease Control and Prevention and the Immunization Practices Advisory Committee.

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PURPOSE: To compare the drainage efficiency of double-lumen sump catheters and single-lumen catheters in an in vitro model. MATERIALS AND METHODS: Four 12-F, 27.5-cm catheters were used in the study. Three of these had a double lumen with a 7-F internal diameter drainage lumen and one had a single lumen with an 8-F internal diameter drainage lumen. The sump hole opened internally to the drainage lumen in one catheter, opened externally in one catheter, and was occluded in one catheter. Catheters were connected to continuous low-wall suction and were immersed in water, viscous fluid, and viscous fluid with particles. The volume of fluid drained by each catheter was measured and compared. RESULTS: The single-lumen catheter with an 8-F internal diameter drainage lumen drained a volume equal to or larger than that for double-lumen catheters with a 7-F internal diameter drainage lumen for each type of fluid. The open sump of the double-lumen catheters may have decreased the catheter's drainage efficiency by allowing air to be suctioned into the catheter. CONCLUSION: Single-lumen catheters performed as well as or more efficiently than double-lumen catheters of the same outer diameter in this in vitro model.

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An investigation of DNA-protein interactions by capillary electrophoresis (CE) with laser fluorometric detection is performed that combines the rapid and minimal sample consumption methods of CE with the selective separation influence of mobility shift assays. An inspection of the well characterized interaction between the trp repressor of Escherichia coli and the trp operator (DNA) is the basis of the assay. The use of fluorescently tagged operator not only lends itself to laser-induced fluorescence detection but also precludes the use of radiolabeled detection. It is demonstrated that composition and pH of the running buffer are critical for maximized efficiency and resolution of operator from the repressor-operator complex. Quantitative studies showed reaction of repressor with operator resulted in the diminishing of free operator signal and the simultaneous creation of the repressor-operator peak that is well resolved from the free operator. Also examined was the ability to perform qualitative studies involving non-specific interactions between the operator and a complex protein sample. It is shown that the specificity of operator for repressor can be used to selectively separate the repressor from a complex sample that includes non-specific proteins.

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Our study was aimed at comparing the therapeutic efficiency of single and double lumen catheters in the drainage of abdominal fluid collections. We report the results of in vitro and in vivo studies carried out to assess the usefulness of each catheter type based on its therapeutic results. In the in vitro study the aspiration efficacy of the catheters was tested in a simulated cavity. In the in vivo study 188 patients with 206 fluid collections in the abdomen were examined; the patients had been treated percutaneously with single or double lumen catheters, randomly. In each patient we studied drainage efficiency related to aspiration efficacy, the time the catheter rested in the cavity, patient's discomfort and finally the cost of both the device and hospitalization. Some patients underwent surgery for specific reasons, but nevertheless their clinical conditions were absolutely improved thanks to percutaneous drainage. The results of this study yield useful clinical data to choose the most suitable catheter for the percutaneous treatment of abdominal fluid collections. Single lumen catheters work better than double lumen ones, the latter being also more expensive. Hospitalization time is also reduced when single lumen catheters are used.

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Extracts of liver and spleen were used to isolate opossum adenosine deaminase isoenzymes (ADA1 and ADA2) and to determine their activities with adenosine and 2'-deoxyadenosine as substrates. Km values (microM) for adenosine and 2'-deoxyadenosine, respectively, as substrates for partially purified opossum liver adenosine deaminase isoenzymes were ADA1: 57 +/- 7 vs. 26 +/- 4 and ADA2: 285 +/- 25 vs. 580 +/- 92. In crude spleen extract, ADA2 activity was stable at 56 degrees C during 40 min of incubation. ADA1 activity declined in a linear fashion under the above conditions with an apparent T1/2 of 80 min. Sephadex G-150 column chromatography of crude spleen extract showed the apparent molecular weight of the ADA activity not inhibited by (+/-)-EHNA (i.e. ADA2) to be 170 kDa; ADA activity fully inhibited by (+/-)-EHNA (i.e. ADA1) eluted in the fractions corresponding to a molecular weight of 35 kDa.

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PURPOSE: To test the technical feasibility and results of placement of metal stents into ureters obstructed by extensive tumor. MATERIALS AND METHODS: Six consecutive patients (two men and four women, aged 35-66 years and with incurable malignancies) underwent insertion of metallic endoprostheses in nine obstructed ureters through percutaneous tracts. RESULTS: Metal stents were inserted without technical difficulty in all obstructed ureters. The stents functioned well in four patients. In two patients, the metal were not tolerated and plastic double-J stents were placed through the metal stents; this permitted effective functioning and withdrawal of the protective external catheter. Intraluminal ultrasonography depicted stent clogging and debris, dimensions of stent opening, and tumor level. CONCLUSION: Insertion of metal stents in the ureter is technically straightforward and was well tolerated by patients. However, the efficacy is variable, and a greater beneficial effect than is achieved with plastic stents is not established.

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PURPOSE: To determine the most accurate imaging modality for detection of silicone implant ruptures. MATERIALS AND METHODS: Forty single-lumen silicone implants were surgically placed in 20 rabbits. Each rabbit received one intact and one ruptured implant and was examined with mammography, magnetic resonance (MR) imaging, ultrasound (US), and computed tomography (CT). Five radiologists reviewed all images in a random fashion and graded each for rupture. The radiologist who performed US also graded her impression during examination with US. Receiver operating characteristic (ROC) analysis was performed. RESULTS: MR imaging and CT were the most accurate modalities in detection of implant ruptures, with areas under the ROC curves (Az) of .95 and .91. Mammography and US were statistically significantly inferior, with Az of .77 for each (P < .05). CONCLUSION: MR imaging and CT are statistically more accurate than US and mammography for detection of intracapsular silicone implant ruptures when only the images are reviewed.

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A method has been developed to follow the decay of the antibiotic penicillin, specifically penicillin G or benzylpenicillin, in the gastric contents of laboratory rats. Purification by centrifugation and DEAE cellulose treatment of the stomach contents (diluted with pH 9 phosphate-borate buffer) was sufficient to allow the quantification of penicillin by capillary zone electrophoresis. An internal standard was used to minimize the injection error. The loss of activity was greater in fasted animals, as expected from the lower pH of their gastric contents, than in fed rats. The in vivo kinetics of the decomposition of the antibiotic was compared to that obtained in water and in hydrochloric acid solutions.

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A simple, rapid colorimetric method is described which determines procainamide in commercially available, injectable solutions. It is based on complexing the drug with cupric ion and then measuring the absorption at 380 nm. The reaction is fast and the metal-drug ratio in the complex is 1:1. The pH optimum for maximum reaction is 4.0-4.5 which is maintained by an acetate buffer. Linear standard curves were obtained from 1.52 to 6.06 mg/mL. Analysis of 29 commercial samples resulted in an average of 97.3% of the label claim.

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A study of the reaction of BF3-methanol with benzylpenicillin showed that penicillin could be converted to a form suitable for gas-liquid chromatography. This study indicated possible use of the reaction in an analytical method for penicillin, by determining the methyl phenylacetate product. A reaction rate and yield study was conducted using gas-liquid chromatography employing an internal standard for improved measurement accuracy. The reaction gave a relatively constant yield of 70 +/- 2% and was complete in less than 1 minute. Investigations of the identity of side products were conducted using GC/MS, UV, and IR. A variety of products, including penicillenates, penillates, penilloates, and acrylic acid esters, were indicated at very mild reaction conditions.

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