Whey protein processing influences formula-induced gut maturation in preterm pigs.

PubMed

Li, Yanqi; Østergaard, Mette V; Jiang, Pingping; Chatterton, Dereck E W; Thymann, Thomas; Kvistgaard, Anne S; Sangild, Per T

2013-12-01

Immaturity of the gut predisposes preterm infants to nutritional challenges potentially leading to clinical complications such as necrotizing enterocolitis. Feeding milk formulas is associated with greater risk than fresh colostrum or milk, probably due to loss of bioactive proteins (e.g., immunoglobulins, lactoferrin, insulin-like growth factor, transforming growth factor-β) during industrial processing (e.g., pasteurization, filtration, spray-drying). We hypothesized that the processing method for whey protein concentrate (WPC) would affect gut maturation in formula-fed preterm pigs used as a model for preterm infants. Fifty-five caesarean-delivered preterm pigs were distributed into 4 groups given 1 of 4 isoenergetic diets: formula containing conventional WPC (filtration, multi-pasteurization, standard spray-drying) (CF); formula containing gently treated WPC (reduced filtration and pasteurization, gentle spray-drying) (GF); formula containing minimally treated WPC (rennet precipitation, reduced filtration, heat treatment <40°C, freeze-drying) (MF); and bovine colostrum (used as a positive reference group) (BC). Relative to CF, GF, and MF pigs, BC pigs had greater villus heights, lactose digestion, and absorption and lower gut permeability (P < 0.05). MF and BC pigs had greater plasma citrulline concentrations than CF and GF pigs and intestinal interleukin-8 was lower in BC pigs than in the other groups (P < 0.05). MF pigs had lower concentrations of intestinal claudin-4, cleaved caspase-3, and phosphorylated c-Jun than CF pigs (P < 0.05). The conventional and gently treated WPCs had similar efficacy in stimulating proliferation of porcine intestinal epithelial cells. We conclude that processing of WPC affects intestinal structure, function, and integrity when included in formulas for preterm pigs. Optimization of WPC processing technology may be important to preserve the bioactivity and nutritional value of formulas for sensitive newborns.

Selective gene amplification to detect the T790M mutation in plasma from patients with advanced non-small cell lung cancer (NSCLC) who have developed epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance.

PubMed

Nishikawa, Shingo; Kimura, Hideharu; Koba, Hayato; Yoneda, Taro; Watanabe, Satoshi; Sakai, Tamami; Hara, Johsuke; Sone, Takashi; Kasahara, Kazuo; Nakao, Shinji

2018-03-01

The epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, tissues for the genotyping of the EGFR T790M mutation can be difficult to obtain in a clinical setting. The aims of this study were to evaluate a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients using the PointMan™ EGFR DNA enrichment kit, which is a novel method for the selective amplification of specific genotype sequences. Blood samples were collected from NSCLC patients who had activating EGFR mutations and who were resistant to EGFR-TKI treatment. Using cell-free DNA (cfDNA) from plasma, EGFR T790M mutations were amplified using the PointMan™ enrichment kit, and all the reaction products were confirmed using direct sequencing. The concentrations of plasma DNA were then determined using quantitative real-time PCR. Nineteen patients were enrolled, and 12 patients (63.2%) were found to contain EGFR T790M mutations in their cfDNA, as detected by the kit. T790M mutations were detected in tumor tissues in 12 cases, and 11 of these cases (91.7%) also exhibited the T790M mutation in cfDNA samples. The concentrations of cfDNA were similar between patients with the T790M mutation and those without the mutation. The PointMan™ kit provides a useful method for determining the EGFR T790M mutation status in cfDNA.

Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma.

PubMed

Kim, Min Kyeong; Woo, Sang Myung; Park, Boram; Yoon, Kyong-Ah; Kim, Yun-Hee; Joo, Jungnam; Lee, Woo Jin; Han, Sung-Sik; Park, Sang-Jae; Kong, Sun-Young

2018-04-01

Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC ( P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC. © 2018 American Association for Clinical Chemistry.

Breath sulfides and pulmonary function in cystic fibrosis.

PubMed

Kamboures, M A; Blake, D R; Cooper, D M; Newcomb, R L; Barker, M; Larson, J K; Meinardi, S; Nussbaum, E; Rowland, F S

2005-11-01

We have determined the concentrations of carbonyl sulfide (OCS), dimethylsulfide, and carbon disulfide (CS(2)) in the breath of a group of cystic fibrosis (CF) patients and one of healthy controls. At the detection sensitivity in these experiments, room air always contained measurable quantities of these three gases. For each subject the inhaled room concentrations were subtracted from the time-coincident concentrations in exhaled breath air. The most significant differences between the CF and control cohorts in these breath-minus-room values were found for OCS. The control group demonstrated a net uptake of 250 +/- 20 parts-per-trillion-by-volume (pptv), whereas the CF cohort had a net uptake of 110 +/- 60 pptv (P = 0.00003). Three CF patients exhaled more OCS than they inhaled from the room. The OCS concentrations in the CF cohort were strongly correlated with pulmonary function. The dimethylsulfide concentrations in breath were greatly enhanced over ambient, but no significant difference was observed between the CF and healthy control groups. The net (breath minus room) CS(2) concentrations for individuals ranged between +180 and -100 pptv. They were slightly greater in the CF cohort (+26 +/- 38 pptv) vs. the control group (-17 +/- 15 pptv; P = 0.04). Lung disease in CF is accompanied by the subsistence of chronic bacterial infections. Sulfides are known to be produced by bacteria in various systems and were therefore the special target for this investigation. Our results suggest that breath sulfide content deserves attention as a noninvasive marker of respiratory colonization.

Analysis of contributing factors associated to related patients safety incidents in Intensive Care Medicine.

PubMed

Martín Delgado, M C; Merino de Cos, P; Sirgo Rodríguez, G; Álvarez Rodríguez, J; Gutiérrez Cía, I; Obón Azuara, B; Alonso Ovies, Á

2015-01-01

To explore contributing factors (CF) associated to related critical patients safety incidents. SYREC study pos hoc analysis. A total of 79 Intensive Care Departments were involved. The study sample consisted of 1.017 patients; 591 were affected by one or more incidents. The CF were categorized according to a proposed model by the National Patient Safety Agency from United Kingdom that was modified. Type, class and severity of the incidents was analyzed. A total 2,965 CF were reported (1,729 were associated to near miss and 1,236 to adverse events). The CF group more frequently reported were related patients factors. Individual factors were reported more frequently in near miss and task related CF in adverse events. CF were reported in all classes of incidents. The majority of CF were reported in the incidents classified such as less serious, even thought CF patients factors were associated to serious incidents. Individual factors were considered like avoidable and patients factors as unavoidable. The CF group more frequently reported were patient factors and was associated to more severe and unavoidable incidents. By contrast, individual factors were associated to less severe and avoidable incidents. In general, CF most frequently reported were associated to near miss. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.

PubMed

Nagy, Béla; Nagy, Béla; Fila, Libor; Clarke, Luka A; Gönczy, Ferenc; Bede, Olga; Nagy, Dóra; Újhelyi, Rita; Szabó, Ágnes; Anghelyi, Andrea; Major, Miklós; Bene, Zsolt; Fejes, Zsolt; Antal-Szalmás, Péter; Bhattoa, Harjit Pal; Balla, György; Kappelmayer, János; Amaral, Margarida D; Macek, Milan; Balogh, István

2016-09-01

Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Nitrites and nitrates in exhaled breath condensate in cystic fibrosis: relation to clinical parameters.

PubMed

Fila, L; Chladek, J; Maly, M; Musil, J

2013-01-01

To evaluate correlation of exhaled breath condensate (EBC) nitrite and nitrate concentrations with disease severity in cystic fibrosis (CF) patients. Nitrites and nitrates are products of oxidative metabolism of nitric oxide. Impaired metabolism of nitric oxide plays a role in pathogenesis of CF. EBC was collected from 46 stable CF patients and from 21 healthy controls. EBC concentrations of nitrites and nitrates were correlated with parameters of lung disease and nutritional status and with systemic inflammatory markers. EBC nitrates concentrations in CF patients were lower than in healthy subjects (5.8 vs 14.3 μmol/l, p<0.001). They correlated positively with FEV1 (p=0.025) and serum albumin values (p=0.016) and negatively with chest radiograph Northern score (p=0.015) and serum C-reactive protein values (p=0.005). EBC nitrites concentrations in CF patients did not differ from those in healthy subjects and were not correlated to any studied parameter. EBC nitrates concentrations correlate with disease severity in CF patients and are lower than in healthy subjects (Tab. 4, Fig. 1, Ref. 48).

The impact of metallic coagulants on the removal of organic compounds from oil sands process-affected water.

PubMed

Pourrezaei, Parastoo; Drzewicz, Przemysław; Wang, Yingnan; Gamal El-Din, Mohamed; Perez-Estrada, Leonidas A; Martin, Jonathan W; Anderson, Julie; Wiseman, Steve; Liber, Karsten; Giesy, John P

2011-10-01

Coagulation/flocculation (CF) by use of alum and cationic polymer polyDADMAC, was performed as a pretreatment for remediation of oil sands process-affected water (OSPW). Various factors were investigated and the process was optimized to improve efficiency of removal of organic carbon and turbidity. Destabilization of the particles occurred through charge neutralization by adsorption of hydroxide precipitates. Scanning electron microscope images revealed that the resultant flocs were compact. The CF process significantly reduced concentrations of naphthenic acids (NAs) and oxidized NAs by 37 and 86%, respectively, demonstrating the applicability of CF pretreatment to remove a persistent and toxic organic fraction from OSPW. Concentrations of vanadium and barium were decreased by 67-78% and 42-63%, respectively. Analysis of surface functional groups on flocs also confirmed the removal of the NAs compounds. Flocculation with cationic polymer compared to alum, caused toxicity toward the benthic invertebrate, Chironoums dilutus, thus application of the polymer should be limited.

Complement Effectors of Inflammation in Cystic Fibrosis Lung Fluid Correlate with Clinical Measures of Disease.

PubMed

Sass, Laura A; Hair, Pamela S; Perkins, Amy M; Shah, Tushar A; Krishna, Neel K; Cunnion, Kenji M

2015-01-01

In cystic fibrosis (CF), lung damage is mediated by a cycle of obstruction, infection, and inflammation. Here we explored complement inflammatory effectors in CF lung fluid. In this study soluble fractions (sols) from sputum samples of 15 CF patients were assayed for complement effectors and analyzed with clinical measurements. The pro-inflammatory peptide C5a was increased 4.8-fold (P = 0.04) in CF sols compared with controls. Incubation of CF sols with P. aeruginosa or S. aureus increased C5a concentration 2.3-fold (P = 0.02). A peptide inhibitor of complement C1 (PIC1) completely blocked the increase in C5a concentration from P. aeruginosa in CF sol in vitro (P = 0.001). C5a concentration in CF sol correlated inversely with body mass index (BMI) percentile in children (r = -0.77, P = 0.04). C3a, which has anti-inflammatory effects, correlated positively with FEV1% predicted (rs = 0.63, P = 0.02). These results suggest that complement effectors may significantly impact inflammation in CF lung fluid.

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis.

PubMed

Collaco, Joseph M; Blackman, Scott M; Raraigh, Karen S; Corvol, Harriet; Rommens, Johanna M; Pace, Rhonda G; Boelle, Pierre-Yves; McGready, John; Sosnay, Patrick R; Strug, Lisa J; Knowles, Michael R; Cutting, Garry R

2016-12-01

Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation. To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling. Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H 2  = 0; 95% confidence interval, 0.0-0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%). Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR.

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis

PubMed Central

Blackman, Scott M.; Raraigh, Karen S.; Corvol, Harriet; Rommens, Johanna M.; Pace, Rhonda G.; Boelle, Pierre-Yves; McGready, John; Sosnay, Patrick R.; Strug, Lisa J.; Knowles, Michael R.; Cutting, Garry R.

2016-01-01

Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation. Objectives: To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. Methods: A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling. Measurements and Main Results: Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H2 = 0; 95% confidence interval, 0.0–0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%). Conclusions: Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR. PMID:27258095

Decoupling between the response of coral calcifying fluid pH and calcification to ocean acidification.

PubMed

Comeau, S; Cornwall, C E; McCulloch, M T

2017-08-08

Evaluating the factors responsible for differing species-specific sensitivities to declining seawater pH is central to understanding the mechanisms via which ocean acidification (OA) affects coral calcification. We report here the results of an experiment comparing the responses of the coral Acropora yongei and Pocillopora damicornis to differing pH levels (8.09, 7.81, and 7.63) over an 8-week period. Calcification of A. youngei was reduced by 35% at pH 7.63, while calcification of P. damicornis was unaffected. The pH in the calcifying fluid (pH cf ) was determined using δ 11 B systematics, and for both species pH cf declined slightly with seawater pH, with the decrease being more pronounced in P. damicornis. The dissolved inorganic carbon concentration at the site of calcification (DIC cf ) was estimated using geochemical proxies (B/Ca and δ 11 B) and found to be double that of seawater DIC, and increased in both species as seawater pH decreased. As a consequence, the decline of the saturation state at the site of calcification (Ω cf ) with OA was partially moderated by the DIC cf increase. These results highlight that while pH cf , DIC cf and Ω cf are important in the mineralization process, some corals are able to maintain their calcification rates despite shifts in their calcifying fluid carbonate chemistry.

Direct measurements of rate coefficients for thermal decomposition of CF3I using shock—tube ARAS technique

NASA Astrophysics Data System (ADS)

Bystrov, N. S.; Emelianov, A. V.; Eremin, A. V.; Yatsenko, P. I.

2018-05-01

The kinetics of the dissociation of CF3I behind shock waves was experimentally investigated. The reaction CF3I  +  Ar  →  CF3  +  I  +  Ar was studied at temperatures between 900 and 1250 K and pressures of 2–3 bar. For this purpose, the time profiles of the concentration of atomic iodine were measured using a highly sensitive atomic resonance absorption spectroscopy method at a wavelength of 183.04 nm. From these data, the experimental value of the dissociation rate constant of CF3I was obtained: . We found that the investigated range of pressures and temperatures for the CF3I dissociation lies in the pressure transition region. Based on the Rice-Ramsperger–Kassel–Marcus theory, the threshold high and low-pressure rate constants ( and k 0) and falloff curves are calculated for the temperatures of 950–1200 K. As a result of this calculation, the threshold rate constants could be evaluated in the forms: and , and the center broadening factor, which takes into account the contribution of strong and weak collisions in the transition region, is .

Cell-Free circulating DNA: a new biomarker for the acute coronary syndrome.

PubMed

Cui, Ming; Fan, Mengkang; Jing, Rongrong; Wang, Huimin; Qin, Jingfeng; Sheng, Hongzhuan; Wang, Yueguo; Wu, Xinhua; Zhang, Lurong; Zhu, Jianhua; Ju, Shaoqing

2013-01-01

In recent studies, concentrations of cell-free circulating DNA (cf-DNA) have been correlated with clinical characteristics and prognosis in several diseases. The relationship between cf-DNA concentrations and the acute coronary syndrome (ACS) remains unknown. Moreover, no data are available for the detection cf-DNA in ACS by a branched DNA (bDNA)-based Alu assay. The aim of the present study was to investigate cf-DNA concentrations in ACS and their relationship with clinical features. Plasma cf-DNA concentrations of 137 ACS patients at diagnosis, of 60 healthy individuals and of 13 patients with stable angina (SA) were determined using a bDNA-based Alu assay. ACS patients (median 2,285.0, interquartile range 916.4-4,857.3 ng/ml), especially in ST-segment elevation myocardial infarction patients (median 5,745.4, interquartile range 4,013.5-8,643.9 ng/ml), showed a significant increase in plasma cf-DNA concentrations compared with controls (healthy controls: median 118.3, interquartile range 81.1-221.1 ng/ml; SA patients: median 202.3, interquartile range 112.7-256.1 ng/ml) using a bDNA-based Alu assay. Moreover, we found positive correlations between cf-DNA and Gensini scoring and GRACE (Global Registry of Acute Coronary Events) scoring in ACS. cf-DNA may be a valuable marker for diagnosing and predicting the severity of coronary artery lesions and risk stratification in ACS. Copyright © 2013 S. Karger AG, Basel.

Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

PubMed

Maes, Michael; Twisk, Frank N M; Johnson, Cort

2012-12-30

There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli

PubMed Central

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue. PMID:26517723

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli.

PubMed

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue.

Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise.

PubMed

Decroix, Lieselot; Tonoli, Cajsa; Soares, Danusa D; Tagougui, Semah; Heyman, Elsa; Meeusen, Romain

2016-12-01

Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO 2 ), deoxygenated (ΔHHb), and total haemoglobin (ΔHb tot ) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO 2 during the resting CT was increased by CF, compared with PL. ΔHbO 2 , ΔHHb, and ΔHb tot increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.

Altered erythrocyte sodium-lithium counter-transport and Na+/K(+)-ATPase activity in cystic fibrosis.

PubMed

Luczay, A; Vásárhelyi, B; Dobos, M; Holics, K; Ujhelyi, R; Tulassay, T

1997-03-01

Patients with cystic fibrosis (CF) exhibit normal concentrations of sodium and chloride in spite of the disturbance of Cl- and Na+ transport in epithelial cells. To characterize compensatory mechanisms in the regulation of sodium homeostasis, erythrocytes of 13 CF patients were analysed for sodium-lithium counter-transport (SLC), Na+/K(+)-ATPase activity and intracellular sodium content. Values were compared to those of healthy controls. Patients with CF had normal serum sodium and chloride concentrations and renal excretions of these ions were within the physiological range. Intracellular sodium concentration was similar in the CF and the control group (6.8 +/- 2.2 vs 5.7 +/- 1.0 mmol/l RBCs). Red blood cells' SLC and Na+/ K(+)-ATPase activity were elevated in CF patients (381 +/- 106 mumol/h/l RBCs vs 281 +/- 64; p < 0.01) and (445 +/- 129 mumol ATP mg prot/h vs 322 +/- 84, p < 0.01). Our study demonstrates that transmembrane cation transport systems are highly activated in CF. The increased sodium transport may be part of a compensatory mechanism of sodium homeostasis in children with CF.

Uptake of dissolved inorganic and organic nitrogen by the benthic toxic dinoflagellate Ostreopsis cf. ovata.

PubMed

Jauzein, Cécile; Couet, Douglas; Blasco, Thierry; Lemée, Rodolphe

2017-05-01

Environmental factors that shape dynamics of benthic toxic blooms are largely unknown. In particular, for the toxic dinoflagellate Ostreopsis cf. ovata, the importance of the availability of nutrients and the contribution of the inorganic and organic pools to growth need to be quantified in marine coastal environments. The present study aimed at characterizing N-uptake of dissolved inorganic and organic sources by O. cf. ovata cells, using the 15 N-labelling technique. Experiments were conducted taking into account potential interactions between nutrient uptake systems as well as variations with the diel cycle. Uptake abilities of O. cf. ovata were parameterized for ammonium (NH 4 + ), nitrate (NO 3 - ) and N-urea, from the estimation of kinetic and inhibition parameters. In the range of 0 to 10μmolNL -1 , kinetic curves showed a clear preference pattern following the ranking NH 4 + >NO 3 - >N-urea, where the preferential uptake of NH 4 + relative to NO 3 - was accentuated by an inhibitory effect of NH 4 + concentration on NO 3 - uptake capabilities. Conversely, under high nutrient concentrations, the preference for NH 4 + relative to NO 3 - was largely reduced, probably because of the existence of a low-affinity high capacity inducible NO 3 - uptake system. Ability to take up nutrients in darkness could not be defined as a competitive advantage for O. cf. ovata. Species competitiveness can also be defined from nutrient uptake kinetic parameters. A strong affinity for NH 4 + was observed for O. cf. ovata cells that may partly explain the success of this toxic species during the summer season in the Bay of Villefranche-sur-mer (France). Copyright © 2017 Elsevier B.V. All rights reserved.

Malabsorption Blood Test: Assessing Fat Absorption in Patients with Cystic Fibrosis and Pancreatic Insufficiency

PubMed Central

Mascarenhas, Maria R.; Mondick, John; Barrett, Jeffrey S.; Wilson, Martha; Stallings, Virginia A.; Schall, Joan I.

2015-01-01

The Malabsorption Blood Test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of one compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration [1.07 (0.827,1.42)] and with enzymes [0.88 (0.72,1.09)] indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192,0.0459), and with enzymes increased to 0.606 (0.482,0.823). In CF, compared to taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664,0.979) and 0.78 (0.491,1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses. PMID:25689042

Circulating cell-free DNA: an up-coming molecular marker in exercise physiology.

PubMed

Breitbach, Sarah; Tug, Suzan; Simon, Perikles

2012-07-01

The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.

Contaminant concentration in environmental samples using LIBS and CF-LIBS

NASA Astrophysics Data System (ADS)

Pandhija, S.; Rai, N. K.; Rai, A. K.; Thakur, S. N.

2010-01-01

The present paper deals with the detection and quantification of toxic heavy metals like Cd, Co, Pb, Zn, Cr, etc. in environmental samples by using the technique of laser-induced breakdown spectroscopy (LIBS) and calibration-free LIBS (CF-LIBS). A MATLABTM program has been developed based on the CF-LIBS algorithm given by earlier workers and concentrations of pollutants present in industrial area soil have been determined. LIBS spectra of a number of certified reference soil samples with varying concentrations of toxic elements (Cd, Zn) have been recorded to obtain calibration curves. The concentrations of Cd and Zn in soil samples from the Jajmau area, Kanpur (India) have been determined by using these calibration curves and also by the CF-LIBS approach. Our results clearly demonstrate that the combination of LIBS and CF-LIBS is very useful for the study of pollutants in the environment. Some of the results have also been found to be in good agreement with those of ICP-OES.

Evidence for crustal degassing of CF4 and SF6 in Mojave Desert groundwaters

USGS Publications Warehouse

Deeds, D.A.; Vollmer, M.K.; Kulongoski, J.T.; Miller, B.R.; Muhle, J.; Harth, C.M.; Izbicki, J.A.; Hilton, David R.; Weiss, R.F.

2008-01-01

Dissolved tetrafluoromethane (CF4) and sulfur hexafluoride (SF6) concentrations were measured in groundwater samples from the Eastern Morongo Basin (EMB) and Mojave River Basin (MRB) located in the southern Mojave Desert, California. Both CF4 and SF6 are supersaturated with respect to equilibrium with the preindustrial atmosphere at the recharge temperatures and elevations of the Mojave Desert. These observations provide the first in situ evidence for a flux of CF4 from the lithosphere. A gradual basin-wide enhancement in dissolved CF4 and SF6 concentrations with groundwater age is consistent with release of these gases during weathering of the surrounding granitic alluvium. Dissolved CF4 and SF6 concentrations in these groundwaters also contain a deeper crustal component associated with a lithospheric flux entering the EMB and MRB through the underlying basement. The crustal flux of CF4, but not of SF6, is enhanced in the vicinity of local active fault systems due to release of crustal fluids during episodic fracture events driven by local tectonic activity. When fluxes of CF4 and SF6 into Mojave Desert groundwaters are extrapolated to the global scale they are consistent, within large uncertainties, with the fluxes required to sustain the preindustrial atmospheric abundances of CF4 and SF6. ?? 2007 Elsevier Ltd. All rights reserved.

Effect of concentrate feeder design on performance, eating and animal behavior, welfare, ruminal health, and carcass quality in Holstein bulls fed high-concentrate diets.

PubMed

Verdú, M; Bach, A; Devant, M

2015-06-01

A total of 240 Holstein bulls (121 ± 2.0 kg initial BW; 99 ± 1.0 d of age), from 2 consecutive fattening cycles, were randomly allocated in 1 of 6 pens and assigned to 1 of the 3 treatments consisting of different concentrate feeder designs: a control feeder with 4 feeding spaces (CF), a feeder with less concentrate capacity (CFL), and a single-space feeder with lateral protections (SF). Each pen had a straw feeder and a drinker. All animals were fed a high-concentrate diet for ad libitum intake. Concentrate consumption was recorded daily using a computerized feeder, straw consumption was recorded weekly, and BW was recorded every 14 d. Animal behavior was registered on d 1, 3, 5, 8, and 14 and every 28 d by scan sampling. Eating behavior at concentrate feeders was filmed on d 12, 125, and 206. On d 7, 120, and 204, samples of rumen contents were collected for measurement of pH and VFA and blood samples were obtained to analyze NEFA, haptoglobin, glucose, and insulin. Animals were slaughtered after 223 d, and HCW and lesions of the rumen wall and liver were recorded. The accumulative concentrate consumption per animal tended (P = 0.09) to be greater with CF than with CFL and SF. Also, CV of concentrate consumption was greater (P < 0.01) for SF than for CF or CFL. However, feeder design did not influence the other performance and carcass data. Also, no differences among treatments in rumen wall evaluation and liver abscesses were observed. At 7 and 204 d of study, SF bulls had greater (P < 0.05) rumen pH compared with CF and CFL bulls. On d 7, the acetate to propionate ratio from SF was greater (P < 0.05) than for CFL or CF. At d 7, NEFA of SF were greater (P < 0.05) compared with CF and CFL. Bulls fed with CF have the greatest (P < 0.01) concentrate disappearance velocity followed by bulls fed with CFL and finally by bulls fed with SF, and this was associated with different feeding behaviors. Bulls on SF spent more time (P < 0.05) eating straw and exhibited fewer (P < 0.05) displacements at concentrate feeder than CF and CFL bulls. The CFL bulls exhibited (P < 0.01) more attempted mounts and tended (P = 0.10) to exhibit more completed mounts than CF bulls. In conclusion, both alternative feeder designs (CFL and SF) are good strategies to reduce total concentrate consumption without impairing performance, rumen health, or animal welfare in Holstein bulls fed high-concentrate diets. However, at the beginning, there was evidence that animals fed using SF had problems with adaptation.

Levofloxacin pharmacokinetics in adult cystic fibrosis.

PubMed

Lee, Carlton K K; Boyle, Michael P; Diener-West, Marie; Brass-Ernst, Lois; Noschese, Michelle; Zeitlin, Pamela L

2007-03-01

Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several beta-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF. Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated. When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC(24)), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 microg x h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 microg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC(24)/MIC ratio. CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (>/= 750 mg); and establish PK/PD targets for managing PA pulmonary infections.

Acidic pH increases airway surface liquid viscosity in cystic fibrosis

PubMed Central

Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

2016-01-01

Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

PubMed

Vanthanouvong, V; Kozlova, I; Johannesson, M; Nääs, E; Nordvall, S L; Dragomir, A; Roomans, G M

2006-04-01

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL. Copyright (c) 2006 Wiley-Liss, Inc.

Dynamic behaviour of river colloidal and dissolved organic matter through cross-flow ultrafiltration system.

PubMed

Wilding, Andrew; Liu, Ruixia; Zhou, John L

2005-07-01

Through cross-flow filtration (CFF) with a 1-kDa regenerated cellulose Pellicon 2 module, the ultrafiltration characteristics of river organic matter from Longford Stream, UK, were investigated. The concentration of organic carbon (OC) in the retentate in the Longford Stream samples increased substantially with the concentration factor (cf), reaching approximately 40 mg/L at cf 15. The results of dissolved organic carbon (DOC) and colloidal organic carbon (COC) analysis, tracking the isolation of colloids from river waters, show that 2 mg/L of COC was present in those samples and good OC mass balance (77-101%) was achieved. Fluorescence measurements were carried out for the investigation of retentate and permeate behaviour of coloured dissolved organic materials (CDOM). The concentrations of CDOM in both the retentate and permeate increased with increasing cf, although CDOM were significantly more concentrated in the retentate. The permeation model expressing the correlation between log[CDOM] in the permeate and logcf was able to describe the permeation behaviour of CDOM in the river water with regression coefficients (r(2)) of 0.94 and 0.98. Dry weight analysis indicated that the levels of organic colloidal particles were from 49 to 71%, and between 29 and 51% of colloidal particles present were inorganic. COC as a percentage of DOC was found to be 10-16% for Longford Stream samples.

Factors Accounting for a Missed Diagnosis of Cystic Fibrosis After Newborn Screening

PubMed Central

Rock, Michael J.; Levy, Hara; Zaleski, Christina; Farrell, Philip M.

2015-01-01

Summary Newborn screening is a public health policy program involving the centralized testing laboratory, infant and their family, primary care provider, and subspecialist for confirmatory testing and follow-up of abnormal results. Cystic fibrosis (CF) newborn screening has now been enacted in all 50 states and the District of Columbia and throughout many countries in the world. Although CF neonatal screening will identify the vast majority of infants with CF, there are many factors in the newborn screening system that can lead to a missed diagnosis of CF. To inform clinicians, this article summarizes the CF newborn screening system and highlights 14 factors that can account for a missed diagnosis of CF. Care providers should maintain a high suspicion for CF if there are compatible symptoms, regardless of the results of the newborn screening test. These factors in newborn screening programs leading to a missed diagnosis of CF present opportunities for quality improvement in specimen collection, laboratory analysis of immunoreactive tryspinogen (IRT) and CF mutation testing, communication, and sweat testing. PMID:22081556

Vitamin K status in cystic fibrosis patients with liver cirrhosis.

PubMed

Krzyżanowska, Patrycja; Drzymała-Czyż, Sławomira; Pogorzelski, Andrzej; Duś-Żuchowska, Monika; Skorupa, Wojciech; Bober, Lyudmyla; Sapiejka, Ewa; Oralewska, Beata; Rohovyk, Nataliya; Moczko, Jerzy; Nowak, Jan; Wenska-Chyży, Ewa; Rachel, Marta; Lisowska, Aleksandra; Walkowiak, Jarosław

2017-06-01

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

cfDNA as an Earlier Predictor of Exercise-Induced Performance Decrement Related to Muscle Damage.

PubMed

Andreatta, Michely V; Curty, Victor M; Coutinho, João Victor S; Santos, Miguel Ângelo A; Vassallo, Paula F; de Sousa, Nuno F; Barauna, Valério G

2017-11-28

The aims of this study were: a) to evaluate whether cell-free DNA (cfDNA) levels increase immediately after an acute light and heavy resistance exercise (RE) bout, and b) to whether cfDNA levels are associated with functional muscle capacity until 48hrs after exercise session. Twenty healthy volunteers performed 3 sets of the leg press resistance exercise with 80% of 1RM (RE80) or 40% of 1RM (RE40) with similar exercise volume. Blood lactate was measured after completion of the 3 sets. Creatine kinase (CK), cfDNA and jump performance were evaluated before (pre) exercise, immediately post-exercise (Post-0) and every 24hrs until 48hrs. Lactate concentration increased similarly in both groups (RE40, 4.0±1.3mmol/L; RE80, 4.8±1.3mmol/L). No changes were observed in squat jump and countermovement jump performance after RE40, however both jumps remained reduced until 48h in RE80 group. CK concentration increased post-24h only in the RE80 group (Pre: 128.8±73.7U/L to Post-24h: 313.8±116.4U/L). cfDNA concentration increased post-0h only in the RE80 group (Pre, 249.8±82.3ng/mL; Post-0h, 406.3±67.2ng/mL). There was a negative correlation between post-0h cfDNA concentration and post-24h squat jump (r=-0.521; p=0.01) and post-0h cfDNA concentration and post-24h countermovement jump (r=-0.539; p=0.01). cfDNA increases in responsive to RE intensity even when not performed until exhaustion. cfDNA measured immediately after RE is a promising biomarker for muscle performance decrement until 48hrs of a RE bout.

Concentration of polychlorinated biphenyl (PCB) congeners in the muscle of Clarias gariepinus and sediment from inland rivers of southwestern Nigeria and estimated potential human health consequences.

PubMed

Adeogun, Aina O; Chukwuka, Azubuike V; Okoli, Chukwunonso P; Arukwe, Augustine

2016-01-01

The distributions of polychlorinated biphenyl (PCB) congeners were determined in sediment and muscle of the African sharptooth catfish (Clarias gariepinus) from the Ogun and Ona rivers, southwest Nigeria. In addition, the effect of PCB congeners on condition factor (CF) and associated human health risk was assessed using muscle levels for a noncarcinogenic hazard quotient (HQ) calculation. Elevated concentrations of high-molecular-weight (HMW) PCB congeners were detected in sediment and fish downstream of discharge points of both rivers. A significant reduction in fish body weight and CF was observed to correlate with high PCB congener concentrations in the Ona River. A principal component (PC) biplot revealed significant site-related PCB congener distribution patterns for HMW PCB in samples from the Ogun River (71.3%), while the Ona River (42.6%) showed significant PCB congener patterns for low-molecular-weight (LMW) congeners. Biota-sediment accumulation factor (BSAF) was higher downstream for both rivers, presenting PCB congener-specific accumulation patterns in the Ona River. Significant decreases in fish body weight, length and CF were observed downstream compared to upstream in the Ona River. The non-carcinogenic HQ of dioxin-like congener 189 downstream in both rivers exceeded the HQ = 1 threshold for children and adults for both the Ogun and Ona rivers. Overall, our results suggest that industrial discharges contribute significantly to PCB inputs into these rivers, with potential for significant health implications for neighboring communities that utilize these rivers for fishing and other domestic purposes.

Use of Quantity Indicators for Forecasting of Biogeochemical Behavior Sr-90 and Cs-137 in the Conditions of the Combined Pollution of Soils

NASA Astrophysics Data System (ADS)

Lavrentyeva, G. V.; Geshel, I. V.

2012-04-01

From huge number of the radionuclides generated by anthropogenous activity the major value the group of biologically active radionuclides has. First of all, it Sr-90 and Cs-137 which play an important role in various radiological situations. In researches on studying of laws of behavior in environment Sr -90 and Cs-137 the basic attention was given to studying of influence of their chemical analogs Ca and K, instead of stable isotopes Sr and Cs. However, even low concentration of stable isotopes Sr and Cs in soil can influence on biogeochemical behavior of radionuclides. Objects of research: dernovo-podsolic soil, summer barley of grade, stable and radioactive isotopes Sr, Cs. Schemes of experiments provided entering of 8 doses stable Cs and Sr in the range from 0 to 500-750 mg/kg of air-dry weight of soil and 50 kBq of radionuclides on each frequency. Absorption of radionuclides by plants will be defined by two parametres of transport. The first - factor of transition (TF), which characterises level of regulation of process of carrying over of a radionuclide from soil in plants and depends on distribution of an element between the firm and liquid phase, distribution defined in the factor (Kd). The second parametre - factor of concentrating (CF) which characterises biological level of regulation of this process. The increase in quantity of stable Sr in soil leads to an active desorption Sr-90 in a soil solution on all frequency. Kd of Cs-137 on the general background of which decrease in values some increase in factor in the range of 120-225 mg of Cs/kg of soil is observed. Received Kd of radionuclides will well be co-ordinated with the revealed functional dependences between concentration Cs and Sr in soil and specific activity Cs-137 and Sr-90 in a soil solution. Comparison CF of two radionuclides shows that plants absorb Sr-90 from a soil solution actively, than Cs-137. Thus values CF of Sr-90 in the investigated interval of concentration of a stable isotope are in inverse relationship from the element maintenance in a soil solution in all investigated interval of the maintenance of the isotope carrier whereas change similar the indicator for Cs-137 has more difficult dependence. The revealed laws of change of CF studied radionuclides prove to be true the received dependences of accumulation Sr-90 and Cs-137 in barley from specific activity of radionuclides in a soil solution. Values of TF of Sr-90 are in direct dependence on level of the maintenance stable Sr, below similar indicators for Cs-137 in all interval of change of concentration of stable isotopes. It finds reflection in the analysis of functional dependences between concentration of radionuclides in plants and soil. The received values of studied factors completely reflect change of specific activity of radionuclides in a soil solution and their biological availability depending on concentration of their stable isotopes that confirms use possibility in the prognostic purposes of these indicators.

Concentration dependent refractive index of a binary mixture at high pressure.

PubMed

Croccolo, Fabrizio; Arnaud, Marc-Alexandre; Bégué, Didier; Bataller, Henri

2011-07-21

In the present work binary mixtures of varying concentrations of two miscible hydrocarbons, 1,2,3,4-tetrahydronaphtalene (THN) and n-dodecane (C12), are subjected to increasing pressure up to 50 MPa in order to investigate the dependence of the so-called concentration contrast factor (CF), i.e., (∂n/∂c)(p, T), on pressure level. The refractive index is measured by means of a Mach-Zehnder interferometer. The setup and experimental procedure are validated with different pure fluids in the same pressure range. The refractive index of the THN-C12 mixture is found to vary both over pressure and concentration, and the concentration CF is found to exponentially decrease as the pressure is increased. The measured values of the refractive index and the concentration CFs are compared with values obtained by two different theoretical predictions, the well-known Lorentz-Lorenz formula and an alternative one proposed by Looyenga. While the measured refractive indices agree very well with predictions given by Looyenga, the measured concentration CFs show deviations from the latter of the order of 6% and more than the double from the Lorentz-Lorenz predictions.

A Cell Number Counting Factor Regulates Akt/Protein Kinase B To Regulate Dictyostelium discoideum Group Size

PubMed Central

Gao, Tong; Knecht, David; Tang, Lei; Hatton, R. Diane; Gomer, Richard H.

2004-01-01

Little is known about how individual cells can organize themselves to form structures of a given size. During development, Dictyostelium discoideum aggregates in dendritic streams and forms groups of ∼20,000 cells. D. discoideum regulates group size by secreting and simultaneously sensing a multiprotein complex called counting factor (CF). If there are too many cells in a stream, the associated high concentration of CF will decrease cell-cell adhesion and increase cell motility, causing aggregation streams to break up. The pulses of cyclic AMP (cAMP) that mediate aggregation cause a transient translocation of Akt/protein kinase B (Akt/PKB) to the leading edge of the plasma membrane and a concomitant activation of the kinase activity, which in turn stimulates motility. We found that countin− cells (which lack bioactive CF) and wild-type cells starved in the presence of anticountin antibodies (which block CF activity) showed a decreased level of cAMP-stimulated Akt/PKB membrane translocation and kinase activity compared to parental wild-type cells. Recombinant countin has the bioactivity of CF, and a 1-min treatment of cells with recombinant countin potentiated Akt/PKB translocation to membranes and Akt/PKB activity. Western blotting of total cell lysates indicated that countin does not affect the total level of Akt/PKB. Fluorescence microscopy of cells expressing an Akt/PKB pleckstrin homology domain-green fluorescent protein (PH-GFP) fusion protein indicated that recombinant countin and anti-countin antibodies do not obviously alter the distribution of Akt/PKB PH-GFP when it translocates to the membrane. Our data indicate that CF increases motility by potentiating the cAMP-stimulated activation and translocation of Akt/PKB. PMID:15470246

Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.

PubMed

Hussain, Rashida; Shahror, Rami; Karpati, Ferenc; Roomans, Godfried M

2015-01-01

Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

Transuranic biokinetic parameters for marine invertebrates--a review.

PubMed

Ryan, T P

2002-04-01

A catalogue of biokinetic parameters for the transuranic elements plutonium, americium, curium, neptunium, and californium in marine invertebrates is presented. The parameters considered are: the seawater-animal concentration factor (CF); the sediment-animal concentration ratio (CR); transuranic assimilation efficiency; transuranic tissue distribution and transuranic elimination rates. With respect to the seawater-animal CF, authors differ considerably on how they define this parameter and a seven-point reporting system is suggested. Transuranic uptake from sediment by animals is characterised by low CRs. The assimilation efficiencies of transuranic elements in marine invertebrates are high compared to vertebrates and mammals in general and the distribution of transuranics within the body tissue of an animal is dependent on the uptake path. The elimination of transuranics from most species examined conformed to a standard biphasic exponential model though some examples with three elimination phases were identified.

Shock wave and modeling study of the thermal decomposition reactions of pentafluoroethane and 2-H-heptafluoropropane.

PubMed

Cobos, C J; Sölter, L; Tellbach, E; Troe, J

2014-06-07

The thermal decomposition reactions of CF3CF2H and CF3CFHCF3 have been studied in shock waves by monitoring the appearance of CF2 radicals. Temperatures in the range 1400-2000 K and Ar bath gas concentrations in the range (2-10) × 10(-5) mol cm(-3) were employed. It is shown that the reactions are initiated by C-C bond fission and not by HF elimination. Differing conclusions in the literature about the primary decomposition products, such as deduced from experiments at very low pressures, are attributed to unimolecular falloff effects. By increasing the initial reactant concentrations in Ar from 60 to 1000 ppm, a retardation of CF2 formation was observed while the final CF2 yields remained close to two CF2 per C2F5H or three CF2 per C3F7H decomposed. This is explained by secondary bimolecular reactions which lead to comparably stable transient species like CF3H, releasing CF2 at a slower rate. Quantum-chemical calculations and kinetic modeling help to identify the reaction pathways and provide estimates of rate constants for a series of primary and secondary reactions in the decomposition mechanism.

Geochemical assessment of heavy metals pollution in surface sediments of Vellar and Coleroon estuaries, southeast coast of India.

PubMed

Nethaji, S; Kalaivanan, R; Arya Viswam; Jayaprakash, M

2017-02-15

Surface sediments were collected from Vellar and Coleroon estuaries for determine sediment texture, calcium carbonate, organic matter and heavy metals. Pollution indices such as pollution load index (PLI), contamination factor (CF), enrichment factor (EF) and geo-accumulation index (I geo ) were done for this study to know the level of heavy metals pollution in the estuarine ecosystem. Pearson correlation matrix and factor were used to assess the relationship and source of heavy metals in the estuarine sediments. The results of PLI values reveal that the study area was polluted by all the heavy metals. The calculated values of CF and I geo followed the decreasing order Cu>Ni>Pb>Co>Cr>Zn>Mn>Fe and illustrate that Cu, Ni and Pb are contaminated due to anthropogenic sources in both estuaries. Correlation and factor analysis suggest that FeMn oxyhydroxides, organic matter and fine particles are responsible for high concentration of heavy metals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Levofloxacin Pharmacokinetics in Adult Cystic Fibrosis

PubMed Central

Lee, Carlton K. K.; Boyle, Michael P.; Diener-West, Marie; Brass-Ernst, Lois; Noschese, Michelle; Zeitlin, Pamela L.

2007-01-01

Background Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several β-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF. Methods Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated. Results When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC24), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 μg × h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 μg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC24/MIC ratio. Conclusion CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (≥ 750 mg); and establish PK/PD targets for managing PA pulmonary infections. PMID:17356095

Control of pulmonary absorption of water-soluble compounds by various viscous vehicles.

PubMed

Yamamoto, Akira; Yamada, Keigo; Muramatsu, Hideaki; Nishinaka, Asako; Okumura, Shigeki; Okada, Naoki; Fujita, Takuya; Muranishi, Shozo

2004-09-10

Effects of various viscous vehicles on the pulmonary absorption of water-soluble drugs were examined by an in situ pulmonary absorption experiment. Gelatin, polyvinylacohol (PVA), hydroxypropylcellose (HPC), chondroitin sulfate A sodium salt (CS), polyacrylic acid (PAA), methylcellulose #400 (MC400) and hyaluronic acid sodium salt (HA) were used as models of viscous vehicles. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocayanate-labeled dextran with an average molecular weight of 4000 (FD4) were used as water-soluble drugs. The plasma concentration of CF was controlled and regulated in the presence of these viscous vehicles, especially gelatin (1-5%) and polyvinyl alcohol (PVA) 1%. In the pharmacokinetic analysis, the Cmax values of CF significantly decreased, and its Tmax values increased in the presence of these viscous vehicles compared with the control. The MRT and MAT values of CF with these vehicles were significantly higher than those without these vehicles. Therefore, these findings indicated that the viscous vehicles were effective to regulate the absorption rate of CF. On the other hand, the pulmonary absorption of FD4 was not so much affected even in the presence of gelatin and PVA, although PVA slightly decreased MRT value, and significantly decreased Tmax value. Furthermore, we examined the release rate of CF from the cellulose tube containing various concentrations of gelatin. The release rate of CF from the cellulose tube with gelatin was inversely related to the viscosity of gelatin. In addition, the release rate of CF was inversely related to DeltaMAT (DeltaMAT = MATgel(MAT with gelatin)-MATsol(MAT without gelatin)) in the presence of varying concentrations of gelatin. These findings indicated that these viscous vehicles were effective to control the pulmonary absorption of CF, a water-soluble drug with low molecular weight and they might be useful to increase the local concentration of drugs in the lung.

Assessment of the anthropogenic influx of metallic pollutants in the Sefidrud delta, Gilan Province, Iran.

PubMed

Rafiei, Behrouz; Ahmadi-Ghomi, Fatemeh; Karimkhani, Afshin

2017-08-15

Understanding the anthropogenic effects on the Sefidrud delta, the concentration of six metals (Cr, Co, Cu, Ni, Pb and Zn) was measured in two sites included the old Sefidrud delta (Amirabad, 23 samples) and the new Sefidrud delta (Kiashahr, 24 samples). Geoaccumulation Index (I geo ), Enrichment Factor (EF), Contamination Factor (CF) and Pollution Load Index (PLI) were used to determine the metal pollution in all sediment samples. Although the EF, I geo , CF and PLI results in the old delta indicate no significant pollution, sediment samples in the new delta show a considerable pollution. Since the sediment source and the lithology of the Sefidrud River drainage basin did not change in the past 500years, the metal pollution in the new delta must be from anthropogenic sources. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radionuclide concentration processes in marine organisms: A comprehensive review.

PubMed

Carvalho, Fernando P

2018-06-01

The first measurements made of artificial radionuclides released into the marine environment did reveal that radionuclides are concentrated by marine biological species. The need to report radionuclide accumulation in biota in different conditions and geographical areas prompted the use of concentration factors as a convenient way to describe the accumulation of radionuclides in biota relative to radionuclide concentrations in seawater. Later, concentration factors became a tool in modelling radionuclide distribution and transfer in aquatic environments and to predicting radioactivity in organisms. Many environmental parameters can modify the biokinetics of accumulation and elimination of radionuclides in marine biota, but concentration factors remained a convenient way to describe concentration processes of radioactive and stable isotopes in aquatic organisms. Revision of CF values is periodically undertaken by international organizations, such as the International Atomic Energy Agency (IAEA), to make updated information available to the international community. A brief commented review of radionuclide concentration processes and concentration factors in marine organisms is presented for key groups of radionuclides such as fission products, activation products, transuranium elements, and naturally-occurring radionuclides. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantitative analysis of cell-free DNA in ovarian cancer.

PubMed

Shao, Xuefeng; He, Yan; Ji, Min; Chen, Xiaofang; Qi, Jing; Shi, Wei; Hao, Tianbo; Ju, Shaoqing

2015-12-01

The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ovarian tumor cases, and 19 healthy, non-cancerous ovaries. bDNA techniques were used to detect serum cf-DNA concentrations. All data were analyzed using SPSS version 18.0. The cf-DNA levels were significantly increased in the ovarian cancer group compared with those of the benign ovarian tumor group and healthy ovarian group (P<0.01). Furthermore, cf-DNA levels were significantly increased in stage III and IV ovarian cancer compared with those of stages I and II (P<0.01). In addition, cf-DNA levels were significantly increased on the first day post-surgery (P<0.01), and subsequently demonstrated a gradual decrease. In the ovarian cancer group, the area under the receiver operating characteristic curve of cf-DNA and the sensitivity were 0.917 and 88.9%, respectively, which was higher than those of cancer antigen 125 (0.724, 75%) and human epididymis protein 4 (0.743, 80.6%). There was a correlation between the levels of serum cf-DNA and the occurrence and development of ovarian cancer in the patients evaluated. bDNA techniques possessed higher sensitivity and specificity than other methods for the detection of serum cf-DNA in patients exhibiting ovarian cancer, and bDNA techniques are more useful for detecting cf-DNA than other factors. Thus, the present study demonstrated the potential value for the use of bDNA as an adjuvant diagnostic method for ovarian cancer.

Assessment of heavy metal accumulation in two species of Tillandsia in relation to atmospheric emission sources in Argentina.

PubMed

Wannaz, Eduardo D; Carreras, Hebe A; Pérez, Carlos A; Pignata, María L

2006-05-15

The ability of Tillandsia capillaris Ruiz and Pav. f. capillaris and Tillandsia permutata A. Cast. to accumulate heavy metals was evaluated in relation to potential atmospheric emission sources in Argentina. The sampling areas (n=38) were chosen in the province of Córdoba, located in the center of Argentina, and categorized according to land use, anthropogenic activities and/or distance to potential heavy metal emission sources. In each sampling site, pools of 40-50 individuals of each species were made from plants collected along the four cardinal directions. The concentrations of V, Mn, Fe, Co, Ni, Cu, Zn, Pb and Br of these samples were measured by Total Reflection X-Ray Fluorescence (TXRF) analysis with Synchrotron Radiation. Each species was submitted to a cluster analysis in order to discriminate different groups of heavy metals as tracers of natural or anthropogenic sources. A Contamination Factor (CF) was calculated using the concentrations of the elements in each sample compared to their concentrations in the control samples. Finally, the rank coefficients of correlation between the CFs and the categorical variables characteristic of each site (land use and anthropogenic load) were analyzed. A positive correlation was found for T. capillaris between the CFs of V, Mn, Co, Ni, Cu and Zn and the urban-industrial category, whereas the CF values for Zn and Pb were positively correlated with the road category. In T. permutata there was a positive correlation between the CF of Zn and the urban-industrial category and the CF of Pb with the road category. We therefore conclude that T. capillaris is a more efficient metal accumulator in passive biomonitoring studies.

EPAC expression and function in cardiac fibroblasts and myofibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy

In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF weremore » treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac fibroblast. • PKA regulates collagen gel contraction in cardiac myofibroblast.« less

Altered chloride metabolism in cultured cystic fibrosis skin fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mattes, P.M.; Maloney, P.C.; Littlefield, J.W.

1987-05-01

An abnormal regulation of chloride permeability has been described for epithelial cells from patients with cystic fibrosis (CF). To learn more about the biochemical basis of this inherited disease, the authors have studied chloride metabolism in cultured CF fibroblasts by comparing the efflux of /sup 36/Cl/sup -/ from matched pairs of CF and normal fibroblasts. The rate constants describing /sup 36/Cl/sup -/ efflux did not differ between the two cell types, but in each of the four pairs tested the amount of /sup 36/Cl/sup -/ contained within CF cells was consistently reduced, by 25-30%, relative to normal cells. Comparisons ofmore » cell water content and /sup 22/Na/sup +/ efflux showed no differences between the two cell types, suggesting that overall intracellular chloride concentration is lower than normal in CF fibroblasts. Such data suggest that the CF gene defect is expressed in skin fibroblasts and that this defect may alter the regulation of intracellular Cl/sup -/ concentration, perhaps through changes in Cl/sup -/ permeability.« less

Stimulated Nitric Oxide Production and Arginine Deficiency in Cystic Fibrosis Children with Nutritional Failure

PubMed Central

Engelen, Mariëlle PKJ; Com, Gulnur; Luiking, Yvette C; Deutz, Nicolaas EP

2013-01-01

Objective Reduced nitric oxide (NO) concentrations are found in the airways of many patients with cystic fibrosis (CF) and are associated with increased airflow obstruction. We determined whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide production in pediatric patients with CF and nutritional failure. Study design In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline, and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Results Increased arginine clearance was found in patients with CF (p<0.001) whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P<0.001), de novo arginine synthesis, and protein breakdown and synthesis (P<0.05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n=7) had significantly higher NO production (P<0.05), de novo arginine synthesis, citrulline production (P<0.001), and plasma citrulline concentration (P<0.05) and lower plasma arginine concentration (P<0.05) than those without nutritional failure (n=9). Conclusions Nutritional failure in CF is associated with increased NO production. However, upregulation of de novo arginine synthesis and citrulline production was not sufficient to meet the increased arginine needs leading to arginine deficiency. PMID:23419590

Combination of forward osmosis (FO) process with coagulation/flocculation (CF) for potential treatment of textile wastewater.

PubMed

Han, Gang; Liang, Can-Zeng; Chung, Tai-Shung; Weber, Martin; Staudt, Claudia; Maletzko, Christian

2016-03-15

A novel combination of forward osmosis (FO) process with coagulation/flocculation (CF) (FO-CF) has been experimentally conceived for the treatment and reuse of textile wastewater. FO is employed to spontaneously recover water from the wastewater via osmosis and thus effectively reduces its volume with a dramatically enhanced dye concentration. CF is then applied to precipitate and remove dyes from the FO concentrated stream with much improved efficiency and reduced chemical dosage. The FO-CF hybrid system exhibits unique advantages of high water flux and recovery rate, well controlled membrane fouling, high efficiency, and minimal environmental impact. Using a lab-made thin-film composite (TFC) FO membrane, an initial water flux (Jw) of 36.0 L m(-2) h(-1) with a dye rejection of 99.9% has been demonstrated by using 2 M NaCl as the draw solution and synthetic textile wastewater containing multiple textile dyes, inorganic salts and organic additives as the feed under the FO mode. The Jw could be maintained at a high value of 12.0 L m(-2) h(-1) even when the recovery rate of the wastewater reaches 90%. Remarkable reverse fouling behavior has also been observed where the Jw of the fouled membrane can be almost fully restored to the initial value by physical flushing without using any chemicals. Due to the great dye concentration in the FO concentrated wastewater stream, the CF process could achieve more than 95% dye removal with a small dosage of coagulants and flocculants at 500-1000 ppm. The newly developed FO-CF hybrid process may open up new exploration of alternative technologies for the effective treatment and reuse of textile effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental relevant concentrations of a chlorpyrifos commercial formulation affect two neotropical fish species, Cheirodon interruptus and Cnesterodon decemmaculatus.

PubMed

Bonifacio, Alejo Fabian; Ballesteros, María Laura; Bonansea, Rocío Inés; Filippi, Iohanna; Amé, María Valeria; Hued, Andrea Cecilia

2017-12-01

The increase of cultivated areas together with the intensive use of pesticides have greatly contributed to impair the quality of aquatic systems along different areas of South America. The main goal of the present study was to assess the effects of a commercial formulation of chlorpyrifos at environmentally relevant concentrations on two native fish species, Cheirodon interruptus and Cnesterodon decemmaculatus. Adult individuals were exposed during 48 h to the following concentrations: 0.084 nl/l (Ci-Cf 1) and 0.84 nl/l (Ci-CF 2) in C. interruptus (Ci) of Clorfox (CF), and 0.84 nl/l (Cd-CF 1) and 8.4 nl/l (Cd-CF 2) in C. decemmaculatus (Cd). Fish behavior was evaluated through locomotor activity and space usage variables. The activity of acetylcholinesterase (AChE) in brain and muscle, catalase (CAT) and glutathione-S-transferase (GST) in brain, liver, muscle and gills, and aspartate amino-transferase (AST), alanine amino-transferase (ALT), AST/ALT ratio and alkaline phosphatase (ALP) in liver, were measured. Both locomotor activity and space usage varied between the two species studied and between CF treatments. The enzyme activities showed significant variations in CAT for C. interruptus and in CAT, GST, AChE, AST, and AST/ALT for C. decemmaculatus under the exposure conditions. Given that both species responded to CF and the concentrations we tested are environmentally relevant, the presence of this pesticide in freshwater systems could impose a risk for populations of both native fish studied at field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Related factors of dental caries and molar incisor hypomineralisation in a group of children with cystic fibrosis.

PubMed

Peker, S; Mete, S; Gokdemir, Y; Karadag, B; Kargul, B

2014-08-01

To investigate dental caries and molar incisor hypomineralisation (MIH)-related factors such as treatment, diet, brushing and salivary factors in children with cystic fibrosis (CF) compared with healthy peers. A cohort study was performed. This study was performed on 30 CF children comprising patients at the Faculty of Medicine and 30 control children recruited from the Dental School. Salivary factors, dental caries, MIH, daily diet, brushing habits were analysed. Statistical analysis was calculated by SPSS for Windows. Decay missing filled teeth (DMF-T) score was 4.6 ± 4.0 in CF and 7.7 ± 2.7 in control (p = 0.001). 43% of CF children with MIH were found to use antibiotics, but no significant difference in the caries experience was found with antibiotic usage (p > 0.05). DMF-T of CF adolescents (23%) who use Tobramycin was 7 ± 3.5. DMF-T of CF children (20%) who take other antibiotics was 2.5 ± 3.5, but no statistical difference was found (p = 0.054). Saliva pH, salivary flow rate, and buffering capacity were not found statistically significant (p > 0.05). Percentage arithmetic mean value, standard deviation, independent sample t test, Fisher's exact test, Chi-square test and Mann-Whitney U test were used, while a p value of <0.05 was considered statistically significant. Medication and diet could be considered as a risk factor for dental caries and factors such as salivary pH, good oral hygiene could play a protective role for oral health CF children. MIH frequency and lower caries experience seen in CF children could be due to salivary factors or pharmacological treatment they take. The multidisciplinary approach team would be advantageous in the management of children with CF and oral health should be under control during early years of life by paediatric dentists.

Tectonic activity as a significant source of crustal tetrafluoromethane emissions to the atmosphere: observations in groundwaters along the San Andreas Fault

USGS Publications Warehouse

Deeds, Daniel A.; Kulongoski, Justin T.; Muhle, Jens; Weiss, Ray F.

2015-01-01

Tetrafluoromethane (CF4) concentrations were measured in 14 groundwater samples from the Cuyama Valley, Mil Potrero and Cuddy Valley aquifers along the Big Bend section of the San Andreas Fault System (SAFS) in California to assess whether tectonic activity in this region is a significant source of crustal CF4 to the atmosphere. Dissolved CF4 concentrations in all groundwater samples but one were elevated with respect to estimated recharge concentrations including entrainment of excess air during recharge (CreCre; ∼30 fmol kg−1 H2O), indicating subsurface addition of CF4 to these groundwaters. Groundwaters in the Cuyama Valley contain small CF4 excesses (0.1–9 times CreCre), which may be attributed to an in situ release from weathering and a minor addition of deep crustal CF4 introduced to the shallow groundwater through nearby faults. CF4 excesses in groundwaters within 200 m of the SAFS are larger (10–980 times CreCre) and indicate the presence of a deep crustal flux of CF4 that is likely associated with the physical alteration of silicate minerals in the shear zone of the SAFS. Extrapolating CF4 flux rates observed in this study to the full extent of the SAFS (1300 km × 20–100 km) suggests that the SAFS potentially emits (0.3–1)×10−1 kg(0.3–1)×10−1 kg CF4 yr−1 to the Earth's surface. For comparison, the chemical weathering of ∼7.5×104 km2∼7.5×104 km2 of granitic rock in California is estimated to release (0.019–3.2)×10−1 kg(0.019–3.2)×10−1 kg CF4 yr−1. Tectonic activity is likely an important, and potentially the dominant, driver of natural emissions of CF4 to the atmosphere. Variations in preindustrial atmospheric CF4 as observed in paleo-archives such as ice cores may therefore represent changes in both continental weathering and tectonic activity, including changes driven by variations in continental ice cover during glacial–interglacial transitions.

Salivary flow rate and biochemical composition analysis in stimulated whole saliva of children with cystic fibrosis.

PubMed

da Silva Modesto, Karine Barros; de Godói Simões, Jéssica Bueno; de Souza, Amanda Ferreira; Damaceno, Neiva; Duarte, Danilo Antonio; Leite, Mariana Ferreira; de Almeida, Eliete Rodrigues

2015-11-01

It is recognized that cystic fibrosis (CF) patients present a risk for oral diseases, since it affects exocrine glands, and the treatment consists of a carbohydrate-rich diet. Recognizing the protective function of saliva on maintaining oral health, the aim of the study was to evaluate salivary parameters in stimulated whole saliva from children with CF. A case-control study was conducted comparing stimulated whole saliva of healthy (n=28; control group) and CF children (n=21; experimental group). Salivary flow rate, initial pH, buffer capacity (total and in each range of pH), total protein and sialic acid (total, free, and conjugated) concentration, α-amylase and salivary peroxidase activities were evaluated. Data were compared by two-tailed Student t test (95% CI; p ≤ 0.05). CF patients presented a significant reduction in salivary parameters compared with the control group (p ≤ 0.05): salivary flow rate (36%), buffer capacity (pH range from 6.9 to 6.0), sialic acid concentration (total 75%, free 61%, and conjugated 83%); α-amylase and salivary peroxidase activities (55%). Additionally, a significant increase in total protein concentration (180%) of stimulated whole saliva from CF patients was verified compared with the control group (p ≤ 0.05). Children with CF presented significant changes in salivary composition, including salivary flow rate, buffering capacity and protective proteins of the oral cavity, compared with children without CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biodegradation of subsurface oil in a tidally influenced sand beach: Impact of hydraulics and interaction with pore water chemistry

NASA Astrophysics Data System (ADS)

Geng, Xiaolong; Boufadel, Michel C.; Lee, Kenneth; Abrams, Stewart; Suidan, Makram

2015-05-01

The aerobic biodegradation of oil in tidally influenced beaches was investigated numerically in this work using realistic beach and tide conditions. A numerical model BIOMARUN, coupling a multiple-Monod kinetic model BIOB to a density-dependent variably saturated groundwater flow model 2-D MARUN, was used to simulate the biodegradation of low-solubility hydrocarbon and transport processes of associated solute species (i.e., oxygen and nitrogen) in a tidally influenced beach environment. It was found that different limiting factors affect different portions of the beach. In the upper intertidal zone, where the inland incoming nutrient concentration was large (1.2 mg N/L), oil biodegradation occurred deeper in the beach (i.e., 0.3 m below the surface). In the midintertidal zone, a reversal was noted where the biodegradation was fast at shallow locations (i.e., 0.1 m below the surface), and it was due to the decrease of oxygen with depth due to consumption, which made oxygen the limiting factor for biodegradation. Oxygen concentration in the midintertidal zone exhibited two peaks as a function of time. One peak was associated with the high tide, when dissolved oxygen laden seawater filled the beach and a second oxygen peak was observed during low tides, and it was due to pore oxygen replenishment from the atmosphere. The effect of the capillary fringe (CF) height was investigated, and it was found that there is an optimal CF for the maximum biodegradation of oil in the beach. Too large a CF (i.e., very fine material) would attenuate oxygen replenishment (either from seawater or the atmosphere), while too small a CF (i.e., very coarse material) would reduce the interaction between microorganisms and oil in the upper intertidal zone due to rapid reduction in the soil moisture at low tide. This article was corrected on 22 JUN 2015. See the end of the full text for details.

Assessment of biostimulation and bioaugmentation for removing chlorinated volatile organic compounds from groundwater at a former manufacture plant.

PubMed

Zhang, Shu; Hou, Zhen; Du, Xiao-Ming; Li, Dong-Ming; Lu, Xiao-Xia

2016-11-01

Site in a former chemical manufacture plant in China was found contaminated with high level of chlorinated volatile organic compounds (CVOCs). The major contaminants chloroform (CF), 1,2-dichloroethane (1,2-DCA) and vinyl chloride (VC) in groundwater were up to 4.49 × 10 4 , 2.76 × 10 6 and 4.35 × 10 4 μg/L, respectively. Ethene and methane were at concentrations up to 2219.80 and 165.85 μg/L, respectively. To test the hypothesis that the CVOCs in groundwater at this site could be removed via biodegradation, biomarker analyses and microcosm studies were conducted. Dehalococcoides 16S rRNA gene and VC-reductase gene vcrA at densities up to 1.5 × 10 4 and 3.2 × 10 4  copies/L were detected in some of the groundwater samples, providing strong evidence that dechlorinating bacteria were present in the aquifer. Results from the microcosm studies showed that at moderate concentrations (CF about 4000 μg/L and 1,2-DCA about 100 μg/L), CF was recalcitrant under natural condition but was degraded under biostimulation and bioaugmentation, while 1,2-DCA was degraded under all the three conditions. At high concentration (CF about 1,000,000 μg/L and 1,2-DCA about 20,000 μg/L), CF was recalcitrant under all the three treatments and 1,2-DCA was only degraded under bioaugmentation, indicating that high concentrations of contaminants were inhibitory to the bacteria. Electron donors had influence on the degradation of contaminants. Of the four fatty acids (pyruvate, acetate, propionate and lactate) examined, all could stimulate the degradation of 1,2-DCA at both moderate and high concentrations, whereas only pyruvate and acetate could stimulate the degradation of CF at moderate concentration. In the microcosms, the observed first-order degradation rates of CF and 1,2-DCA were up to 0.12 and 0.11/day, respectively. Results from the present study provided scientific basis for remediating CVOCs contaminated groundwater at the site.

Expression pattern of Chlamys farreri sox2 in eggs, embryos and larvae of various stages

NASA Astrophysics Data System (ADS)

Liang, Shaoshuai; Ma, Xiaoshi; Han, Tiantian; Yang, Dandan; Zhang, Zhifeng

2015-08-01

The SOX2 protein is an important transcription factor functioning during the early development of animals. In this study, we isolated a full-length cDNA sequence of scallop Chlamys farreri sox2, Cf-sox2 which was 2194 bp in length with a 981 bp open reading frame encoding 327 amino acids. With real-time PCR analysis, it was detected that Cf-sox2 was expressed in unfertilized oocytes, fertilized eggs and all the tested embryos and larvae. The expression level increased significantly ( P < 0.01) in embryos from 2-cell to blastula, and then decreased significantly ( P < 0.01) and reached the minimum in umbo larva. Moreover, location of the Cf-sox2 expression was revealed using whole mount in situ hybridization technique. Positive hybridization signal could be detected in the central region of unfertilized oocytes and fertilized eggs, and then strong signals dispersed throughout the embryos from 2-cell to gastrula. During larval development, the signals were concentrated and strong signals were restricted to 4 regions of viscera mass in veliger larva. In umbo larva, weak signals could be detected in regions where presumptive visceral and pedal ganglia may be formed. The expression pattern of Cf-sox2 during embryogenesis was similar to that of mammal sox2, which implied that Cf-SOX2 may participate in the regulation of early development of C. farreri.

Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi

PubMed Central

Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.

2011-01-01

To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844

Acute high-intensity interval exercise induces comparable levels of circulating cell-free DNA and Interleukin-6 in obese and normal-weight individuals.

PubMed

Ferrandi, Peter J; Fico, Brandon G; Whitehurst, Michael; Zourdos, Michael C; Bao, Fanchen; Dodge, Katelyn M; Rodriguez, Alexandra L; Pena, Gabriel; Huang, Chun-Jung

2018-06-01

Obesity is associated with lipid aggregation in adipocytes and macrophage infiltration, leading to increased oxidative stress and inflammation. Increased cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of systemic inflammation. While the beneficial effects of regular physical activity on the release of circulating cfDNA still remain unknown, acute intense exercise has been shown to increase inflammatory cytokines and cfDNA concentrations in normal-weight individuals. Therefore, the primary purpose of this study was to examine the effect of acute high-intensity interval Exercise (HIIE) on plasma cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects. Fourteen male subjects (7 obese and 7 normal-weight) participated in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO 2max ) on a treadmill. Between HIIE intervals, subjects performed 3 min of active recovery at 50-60% VO 2max . Blood samples were collected prior to, immediately following exercise, and one hour into recovery for measurements of plasma cfDNA and IL-6. Our results demonstrated a significant elevation in plasma cfDNA immediately following acute HIIE in both obese and normal-weight subjects. A comparable elevation in the concentration of plasma IL-6 was also found between two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was not correlated with IL-6 either at baseline or in response to acute HIIE. These findings may support the utilization of HIIE as a time-efficient exercise protocol to understand the obesity-associated cfDNA and inflammatory responses. Published by Elsevier Inc.

Sensitive electrochemical nonenzymatic glucose sensing based on anodized CuO nanowires on three-dimensional porous copper foam

NASA Astrophysics Data System (ADS)

Li, Zhenzhen; Chen, Yan; Xin, Yanmei; Zhang, Zhonghai

2015-11-01

In this work, we proposed to utilize three-dimensional porous copper foam (CF) as conductive substrate and precursor of in-situ growth CuO nanowires (NWs) for fabricating electrochemical nonenzymatic glucose sensors. The CF supplied high surface area due to its unique three-dimensional porous foam structure, and thus resulted in high sensitivity for glucose detection. The CuO NWs/CF based nonenzymatic sensors presented reliable selectivity, good repeatability, reproducibility, and stability. In addition, the CuO NWs/CF based nonenzymatic sensors have been employed for practical applications, and the glucose concentration in human serum was measured to be 4.96 ± 0.06 mM, agreed well with the value measured from the commercial available glucose sensor in hospital, and the glucose concentration in saliva was also estimated to be 0.91 ± 0.04 mM, which indicated that the CuO NWs/CF owned the possibility for noninvasive glucose detection. The rational design of CuO NWs/CF provided an efficient strategy for fabricating of electrochemical nonenzymatic biosensors.

Sensitive electrochemical nonenzymatic glucose sensing based on anodized CuO nanowires on three-dimensional porous copper foam

PubMed Central

Li, Zhenzhen; Chen, Yan; Xin, Yanmei; Zhang, Zhonghai

2015-01-01

In this work, we proposed to utilize three-dimensional porous copper foam (CF) as conductive substrate and precursor of in-situ growth CuO nanowires (NWs) for fabricating electrochemical nonenzymatic glucose sensors. The CF supplied high surface area due to its unique three-dimensional porous foam structure, and thus resulted in high sensitivity for glucose detection. The CuO NWs/CF based nonenzymatic sensors presented reliable selectivity, good repeatability, reproducibility, and stability. In addition, the CuO NWs/CF based nonenzymatic sensors have been employed for practical applications, and the glucose concentration in human serum was measured to be 4.96 ± 0.06 mM, agreed well with the value measured from the commercial available glucose sensor in hospital, and the glucose concentration in saliva was also estimated to be 0.91 ± 0.04 mM, which indicated that the CuO NWs/CF owned the possibility for noninvasive glucose detection. The rational design of CuO NWs/CF provided an efficient strategy for fabricating of electrochemical nonenzymatic biosensors. PMID:26522446

Electron microprobe analysis of human labial gland secretory granules in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izutsu, K.; Johnson, D.; Schubert, M.

1985-06-01

X-ray microanalysis of freeze-dried labial gland cryosections revealed that Na concentration was doubled and the Ca/S concentration ratio was decreased in secretory granules of labial glands from patients with cystic fibrosis (CF) when compared with glands from normal subjects. Other results suggested that the decrease in the Ca/S concentration ratio resulted from an increase in S concentration. These findings imply that mucous granules in labial saliva showed a CF-related increase in Na and S content, and such changes would be expected to affect the rheology of the mucus after exocytosis. In contrast with a previous study in human parotid glands,more » no evidence was found for CF-related changes in cytoplasmic or nuclear Na, K, and Ca concentrations. Significant elemental differences were found between secretory granules and nuclei and cytoplasm of control cells.« less

Factors affecting ozone sensitivity of tobacco Bel-W3 seedlings.

PubMed

Cheng, Ji-Fang; Sun, En-Jang

2013-12-01

Since 1962, the tobacco variety Nicotiana tabacum cv. Bel-W3 has been used worldwide as an ozone (O3) bio-indicator. The use of indicator plants to monitor O3 pollution has proven problematic when trying to correlate the severity of injury to ambient O3 concentration. The aim of the present study was to study factors affecting the O3 sensitivity of Nicotiana tabacum cv. Bel-W3 seedlings. In chronic O3 pre-exposure tests, tobacco plants were cultured from seeds in charcoal-filtered air (CF) and noncharcoal-filtered ambient air (NF) for 21 days. During these periods, the mean O3 concentrations of the CF and NF treatments were 5.5 ± 0.2 and 14.7 ± 0.4 ppb h -1 , respectively (p < 0.001). At the end of the culturing period, no O3-induced foliar injury was observed in any of the plants. The O3 sensitivity of the tobacco plants was determined by exposing the plants to 150 ppb O3 for 8 hours in a fumigation chamber. The leaf injury index percentages (LII%) of indicator plants via the CF and NF treatments were 58.0 ± 3.2% and 43.1 ± 4.0%, respectively (p < 0.01). Twenty-one-day-old tobacco seedlings grown in NF air were used to test the effects of exposed leaves on O3 sensitivity. After removing the cotyledons and all true leaves, the NF seedlings with their apical buds intact were transferred to CF air. After another 7 days of culturing, the newly developed leaves were approximately 1 cm in length. After O3 treatment, the LII% values of the newly developed leaves from the untreated and defoliated seedlings were 2.5 ± 1.7% and 27.6 ± 1.3%, respectively (p < 0.001). In acute O3 exposure tests, 21-day-old seedlings grown in CF air were fumigated with 150 ppb O3 for 8 hours in one day or for 4 hours/day in two consecutive days. The LII% values for the two groups were 63.5 ± 7.4% and 20.1 ± 4.3%, respectively (p < 0.001). The present findings suggest that plant pre-exposure to O3 is a critical factor influencing O3 sensitivity and that exposed leaves obtain acquired tolerance against O3 injury later on.

Total DNA input is a crucial determinant of the sensitivity of plasma cell-free DNA EGFR mutation detection using droplet digital PCR

PubMed Central

Zhao, Jing; Chen, Minjiang; Zhang, Li; Li, Longyun; Wang, Mengzhao

2017-01-01

We evaluated the use of droplet digital PCR (ddPCR) to detect plasma cell-free DNA (cfDNA) epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients. Compared with tumor-tissue-based detection, the sensitivity of ddPCR for detecting plasma cfDNA tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutations was 61.3%, the specificity was 96.7%, and the consistency rate was 81.4% (?=0.605, 95% confidence interval: 0.501-0.706, p <0.0001). The sensitivity declined from 82.6% to 46.7% with decreasing cfDNA inputs (p=0.028). The plasma cfDNA concentration correlated with gender (males vs.females =11.69 ng/mL vs. 9.508 ng/mL; p=0.044), EGFR mutation status (tumor-tissue EGFR mutation-positive (EGFR M+) vs. EGFR mutation-negative (EGFR M-) = 9.61 ng/mL vs. 12.82 ng/mL; p =0.049) and specimen collection time (=2 years vs. >2 years=13.83 ng/mL vs. 6.575 ng/mL; p <0.001), and was greater in tumor-tissue EGFR M+ / plasma EGFR M+ patients than in tumor-tissue EGFR M+/plasma EGFR M- patients (11.61 vs. 7.73 ng/mL, respectively; p=0.003). Thus total cfDNA input crucially influences the sensitivity of plasma cfDNA EGFR mutation testing with ddPCR. Such analysis could be an effective supplemental test for advanced NSCLC patients. PMID:28052016

Life cycle assessment of milk production from commercial dairy farms: the influence of management tactics.

PubMed

Yan, M-J; Humphreys, J; Holden, N M

2013-07-01

Little consideration has been given to how farm management, specifically tactics used to implement the management strategy, may influence the carbon footprint (CF) and land use for milk produced on commercial farms. In this study, the CF and land use of milk production from 18 Irish commercial dairy farms were analyzed based on foreground data from a 12-mo survey capturing management tactics and background data from the literature. Large variation was found in farm attributes and management tactics; for example, up to a 1.5-fold difference in fertilizer nitrogen input was used to support the same stocking density, and up to a 3.5-fold difference in concentrate fed for similar milk output per cow. However, the coefficient of variation for milk CF between farms only varied by 13% and for land use by 18%. The overall CF and overall land use of the milk production from the 18 dairy farms was 1.23±0.04kg of CO2 Eq and 1.22±0.05 m(2) per kilogram of energy-corrected milk. Milk output per cow, economic allocation between exports of milk and liveweight, and on-farm diesel use per ha were found to be influential factors on milk CF, whereas the fertilizer N rate, milk output per cow, and economic allocation between exports of milk and liveweight were influential on land use. Effective sward management of white clover within a few farms appeared to lower the CF but increased on-farm land use. It was concluded that a combination of multiple tactics determines CF and land use for milk production on commercial dairy farms and, although these 2 measures of environmental impact are correlated, a farm with a low CF did not always have low land use and vice versa. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Radiation and chemistry in the stratosphere - Sensitivity to O2 absorption cross sections in the Herzberg continuum

NASA Technical Reports Server (NTRS)

Froidevaux, L.; Yung, Y. L.

1982-01-01

It is suggested that the discrepancies between observed and modeled vertical profiles of such halocarbons as CFCl3, as well as the problem of simultaneously fitting N2O, CH4, CF2Cl2 and CFCl3 profiles with a single eddy diffusion model, are due to an overestimation of the molecular oxygen absorption cross sections in the 200-220 nm spectral region. The replacement of current O2 cross sections in this range with values that are in better agreement with results for the compounds cited leads to N2O, CF2Cl2 and CFCl3 concentration reductions of factors 0.70, 0.62 and 0.19, respectively. Profiles of CH4, H2 and CO remain unchanged, and the predicted concentration of HNO3 above 30 km is reduced by about 50% for yet another improved fit with observations. It is noted that the correction proposed produces a 30% ozone increase near the 20-25 km peak.

Proteolytic cleavage of the long pentraxin PTX3 in the airways of cystic fibrosis patients.

PubMed

Hamon, Yveline; Jaillon, Sébastien; Person, Christine; Giniès, Jean-Louis; Garo, Erwan; Bottazzi, Barbara; Ghamrawi, Sarah; Urban, Thierry; Subra, Jean-François; Bouchara, Jean-Philippe; Mantovani, Alberto; Jeannin, Pascale; Delneste, Yves

2013-12-01

The prototypic long pentraxin PTX3, a soluble pattern recognition receptor, plays an important role in innate defense against selected pathogens by favoring their elimination and the initiation of protective responses. PTX3 has notably beneficial effects in mice infected with Aspergillus fumigatus and Pseudomonas aeruginosa. Cystic fibrosis (CF), a severe inherited autosomal recessive disease, is characterized by recurrent lung infections, especially by these two pathogens. We thus hypothesized that the status of PTX3 may be altered in CF patients. Level and integrity of PTX3 were analyzed in the sputum samples from 51 CF patients and 7 patients with chronic obstructive pulmonary disease (COPD). The levels of PTX3 were increased in serums from CF patients, but low in their respiratory secretions. PTX3 concentrations in sputum samples were dramatically lower in CF patients than in COPD patients. The low concentration of PTX3 resulted from a proteolysis cleavage by elastase and A. fumigatus proteases. Interestingly, the N-ter domain of PTX3, involved in protection against A. fumigatus, is preferentially degraded by these proteases. These results indicate that the selective proteolysis of PTX3 in the CF lung may explain, in part, the recurrent lung infections by PTX3-sensitive pathogens in CF patients.

Early severe anemia as the first sign of cystic fibrosis.

PubMed

Sismanlar, Tugba; Aslan, Ayşe Tana; Köse, Mehmet; Pekcan, Sevgi; Ezgü, Fatih Süheyl; Budakoğlu, Işıl İrem; Yenicesu, İdil

2016-09-01

Severe anemia is reported to occur rarely in patients with cystic fibrosis (CF). This study aimed to determine the factors associated with early severe anemia in infants with CF. This study included 231 infants with CF from 3 pediatric CF centers ten year period that were retrospectively reviewed in terms of severe anemia as the first sign of CF. Factors that could affect anemia, such as age, pancreatic insufficiency, mutations, vitamin A and E, and albumin level were evaluated. Clinical and laboratory findings in CF patients that presented with severe anemia and no respiratory symptoms were compared to those in CF patients that did not present with severe anemia. Severe anemia as the first sign of CF was noted in 17 of 231 patients. Patient age, prolonged PT/INR and the albumin level differed significantly between the 2 groups of patients (P < 0.001). Feeding pattern, pancreatic insufficiency, vitamin E and A levels, and the types of genetic mutations did not differ between the 2 groups. The mean hemoglobin level was 5.59 ± 0.21 g/dL and respiratory symptoms began a mean 6.3 months after diagnosis of CF in the anemia group. In early infancy severe anemia in the absence of respiratory symptoms can be the first sign of CF. CF should be considered in the differential diagnosis of severe anemia in infants. Anemia can occur several months before respiratory symptoms in patients with CF and may be caused due to several reasons. • Severe anemia as a first sign is reported to occur rarely in patients with cystic fibrosis. • Although anemia is well known in cystic fibrosis, factors that cause severe anemia are not known clearly. What is New: • This study shows the importance of severe anemia as the first sign of cystic fibrosis. • Anemia can occur several months before respiratory symptoms in patients with CF.

Factor Rotation and Standard Errors in Exploratory Factor Analysis

ERIC Educational Resources Information Center

Zhang, Guangjian; Preacher, Kristopher J.

2015-01-01

In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

Distribution of mercury in molluscs, seawaters and coastal sediments of Tarut Island, Arabian Gulf, Saudi Arabia

NASA Astrophysics Data System (ADS)

Youssef, Mohamed; El-Sorogy, Abdelbaset; Al-Kahtany, Khaled

2016-12-01

In order to assess the distribution of mercury along the Tarut coast, Arabian Gulf, Thirty eight (38) sediment samples, twenty six (26) seawater samples, and forty (40) Mollusca specimens were collected from the Tarut coast. The concentrations of Mercury in the sediments of the studied area (average = 0.55 μg/g) are generally high comparing to the reported values from the Gulf of Oman, Red Sea, and the Gulf of Finland. The concentrations of Hg exceeded the wet threshold safety values (median effect concentration (MEC), and probable effect concentration (PEC) indicating possible Hg contamination. According to the Swedish Environmental Protection Agency (SEPA), thirty four (34) samples occur in class 4 and four (4) samples occur in class 5, which means that the sediments of the Tarut Island are largely contaminated with Hg. Enrichment factor (EF) results (average = 1.76) suggested that, the coastal sediments of the Tarut Island are considered to entirely originate from the crustal materials or natural processes. The studied sediments show lower values (Igeo<0) indicating that the sediments are unpolluted. These sediments according to contamination factor (Cf) are considered contaminated with Hg (1 < CF < 3). The Hg concentration in water samples (average = 30 μg/g) considered high. Comparison with Hg contents in coastal sediments, seawaters and molluscs in the Red Sea, the Arabian Gulf suggested that the studied samples have higher concentrations of Hg. The suggested natural sources of Hg in the study area are the weathering and decomposition of neighboring deserts. The anthropogenic sources are the land reclamation, petrochemical industries, boat exhaust emissions, oil leakage, desalination plants and sewage effluents exceeded in the study area and in Al Jubail industrial city to the north.

40 CFR 132.6 - Application of part 132 requirements in Great Lakes States and Tribes.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the State of Indiana. (b) Effective September 5, 2000, the requirements of Procedure 3 in Appendix F... in the States of Indiana, Michigan and Ohio. (d) Effective November 6, 2000, § 132.4(d)(2) shall... a total concentration. (b) Chemical mA bA Conversion factor (CF) Cadmium a,b 1.128 −3.6867 0.85...

40 CFR 132.6 - Application of part 132 requirements in Great Lakes States and Tribes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the State of Indiana. (b) Effective September 5, 2000, the requirements of Procedure 3 in Appendix F... in the States of Indiana, Michigan and Ohio. (d) Effective November 6, 2000, § 132.4(d)(2) shall... a total concentration. (b) Chemical mA bA Conversion factor (CF) Cadmium a,b 1.128 −3.6867 0.85...

Diagnosis of cystic fibrosis with chloride meter (Sherwood M926S chloride analyzer®) and sweat test analysis system (CFΔ collection system®) compared to the Gibson Cooke method.

PubMed

Emiralioğlu, Nagehan; Özçelik, Uğur; Yalçın, Ebru; Doğru, Deniz; Kiper, Nural

2016-01-01

Sweat test with Gibson Cooke (GC) method is the diagnostic gold standard for cystic fibrosis (CF). Recently, alternative methods have been introduced to simplify both the collection and analysis of sweat samples. Our aim was to compare sweat chloride values obtained by GC method with other sweat test methods in patients diagnosed with CF and whose CF diagnosis had been ruled out. We wanted to determine if the other sweat test methods could reliably identify patients with CF and differentiate them from healthy subjects. Chloride concentration was measured with GC method, chloride meter and sweat test analysis system; also conductivity was determined with sweat test analysis system. Forty eight patients with CF and 82 patients without CF underwent the sweat test, showing median sweat chloride values 98.9 mEq/L with GC method, 101 mmol/L with chloride meter, 87.8 mmol/L with sweat test analysis system. In non-CF group, median sweat chloride values were 16.8 mEq/L with GC method, 10.5 mmol/L with chloride meter, and 15.6 mmol/L with sweat test analysis system. Median conductivity value was 107.3 mmol/L in CF group and 32.1 mmol/L in non CF group. There was a strong positive correlation between GC method and the other sweat test methods with a statistical significance (r=0.85) in all subjects. Sweat chloride concentration and conductivity by other sweat test methods highly correlate with the GC method. We think that the other sweat test equipments can be used as reliably as the classic GC method to diagnose or exclude CF.

Intra-individual biological variation in sweat chloride concentrations in CF, CFTR dysfunction, and healthy pediatric subjects.

PubMed

Cirilli, Natalia; Raia, Valeria; Rocco, Ilaria; De Gregorio, Fabiola; Tosco, Antonella; Salvadori, Laura; Sepe, Angela Ornella; Buzzetti, Roberto; Minicuci, Nadia; Castaldo, Giuseppe

2018-04-02

The sweat test is one of the main diagnostic tools used in newborn screening programs and as a confirmatory test, in case of suspect of Cystic Fibrosis (CF). Since sweat chloride (Cl) concentration is also considered an appropriate parameter to explore the efficacy of CFTR modulators in clinical trials, it is crucial to evaluate the biological variability of this test in healthy and pathological conditions. The aim of this pilot study was to determine the intra-individual biological variability of sweat Cl, both in healthy individuals and CF patients and to assess its correlation with diet, season, and menstrual cycle. Thirty-five out of 36 selected subjects (6-18 years) were enrolled by 2 CF care centers and assigned to 3 cohorts: CF, CFTR-related disorder (CFTR-RD) and healthy volunteers. Each participant was subjected to eight sweat tests in different conditions and time of the year. Data were analyzed using linear mixed effects models for repeated measures, taking also into account intra-individual correlations. We observed a high intra-individual variability of sweat Cl, with the lowest mean CV% values among CF patients (20.21 in CF, 29.74 in CFTR-RD, and 31.15 in healthy subjects). Gender and diet had no influence on sweat Cl variability, nor had pubertal age and menstrual phase. Results of this pilot study confirmed that sweat Cl variability is high in CF patients, although non-CF individuals displayed even higher mean CV% values. Season significantly influenced sweat test values only in CF patients, likely due to changes in their hydration status. © 2018 Wiley Periodicals, Inc.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

PubMed

Hammana, I; Malet, A; Costa, M; Brochiero, E; Berthiaume, Y; Potvin, S; Chiasson, J-L; Coderre, L; Rabasa-Lhoret, R

2007-06-01

Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Purification and Characterization of a Glycerol-Resistant CF0-CF1 and CF1-ATPase from the Halotolerant Alga Dunaliella bardawil1

PubMed Central

Finel, Moshe; Pick, Uri; Selman-Reimer, Susanne; Selman, Bruce R.

1984-01-01

The isolation of the chloroplast ATP synthase complex (CF0-CF1) and of CF1 from Dunaliella bardawil is described. The subunit structure of the D. bardawil ATPase differs from that of the spinach in that the D. bardawil α subunit migrates ahead of the β subunit and ε-migrates ahead of subunit II of CF0 when separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The CF1 isolated from D. bardawil resembles the CF1 isolated from Chladmydomonas reinhardi in that a reversible, Mg2+-dependent ATPase is induced by selected organic solvents. Glycerol stimulates cyclic photophosphorylation catalyzed by D. bardawil thylakoid membranes but inhibits photophosphorylation catalyzed by spinach thylakoid membranes. Glycerol (20%) also stimulates the rate of ATP-Pi exchange catalyzed by D. bardawil CF0-CF1 proteoliposomes but inhibits the activity with the spinach enzyme. The ethanol-activated, Mg2+-ATPase of the D. bardawil CF1 is more resistant to glycerol inhibition than the octylglucoside-activated, Mg2+-ATPase of spinach CF1 or the ethanol-activated, Mg2+-dependent ATPase of the C. reinhardi CF1. Both cyclic photophosphorylation and ATP-Pi exchange catalyzed by D. bardawil CF0-CF1 are more sensitive to high concentrations of NaCl than is the spinach complex. Images Fig. 5 PMID:16663507

Effects of copper and butyltin compounds on the growth, photosynthetic activity and toxin production of two HAB dinoflagellates: The planktonic Alexandrium catenella and the benthic Ostreopsis cf. ovata.

PubMed

Couet, Douglas; Pringault, Olivier; Bancon-Montigny, Chrystelle; Briant, Nicolas; Elbaz Poulichet, Françoise; Delpoux, Sophie; Kefi-Daly Yahia, Ons; Hela, BenGharbia; Charaf, M'Rabet; Hervé, Fabienne; Rovillon, Georges; Amzil, Zouher; Laabir, Mohamed

2018-03-01

Controlled laboratory experiments were conducted to test the effects of copper (Cu 2+ ) and butyltins (BuT) on the growth, photosynthetic activity and toxin content of two HABs (Harmful Algal Blooms) dinoflagellates, the planktonic Alexandrium catenella and the benthic Ostreopsis cf. ovata. Microalgae were exposed to increasing concentrations of Cu 2+ (10 -4 to 31 nM) or BuT (0.084 to 84 nM) for seven days. When considering the growth, EC 50 values were 0.16 (±0.09) nM and 0.03 (±0.02) nM of Cu 2+ for A. catenella and O. cf. ovata, respectively. Regarding BuT, EC 50 was 14.2 (±6) nM for O. cf. ovata, while A. catenella growth inhibition appeared at BuT concentrations ≥27 nM. Photosynthetic activity of the studied dinoflagellates decreased with increasing Cu and BuT concentrations. For O. cf. ovata, the response of this physiological parameter to contamination was less sensitive than the biomass. Cu exposure induced the formation of temporary cysts in both organisms that could resist adverse conditions. The ovatoxin-a and -b concentrations in O. cf. ovata cells increased significantly in the presence of Cu. Altogether, the results suggest a better tolerance of the planktonic A. catenella to Cu and BuT. This could result in a differentiated selection pressure exerted by these metals on phytoplankton species in highly polluted waters. The over-production of toxins in response to Cu stress could pose supplementary health and socio-economic threats in the contaminated marine ecosystems where HABs develop. Copyright © 2018 Elsevier B.V. All rights reserved.

The diagnosis of cystic fibrosis.

PubMed

De Boeck, Kris; Vermeulen, Francois; Dupont, Lieven

2017-06-01

Establishing the diagnosis of cystic fibrosis (CF) is straight forward in the majority of patients: they present with a clear clinical picture (most frequently chronic respiratory symptoms plus malabsorption), the sweat chloride value is>60mmol/L and two known disease causing CFTR mutations are identified. In less than 5% of subjects, mainly those with a milder or limited phenotype, the diagnostic process is more complex, because initial diagnostic test results are inconclusive: sweat chloride concentration in the intermediate range, less than 2 CF causing mutations identified or both. These patients should be referred to expert centers where bioassays of CFTR function like nasal potential difference measurement or intestinal current measurement can be done. Still, in some patients, despite symptoms compatible with CF and some indication of CFTR dysfunction (e.g. only intermediate sweat chloride value), diagnostic criteria are not met (e.g. only 1 CFTR mutation identified). For these subjects, the term CFTR related disorder (CFTR-RD) is used. Patients with disseminated bronchiectasis, congenital bilateral absence of the vas deferens and acute or recurrent pancreatitis may fall in this category. CF has a very wide disease spectrum and increasingly the diagnosis is being made during adult life, mainly in subjects with milder phenotypes. In many countries, nationwide CF newborn screening (NBS) has been introduced. In screen positive babies, the diagnosis of CF must be confirmed by a sweat test demonstrating a sweat chloride concentration above 60mmol/L. To achieve the benefit of NBS, every baby in whom the diagnosis of CF is confirmed must receive immediate follow-up and treatment in a CF reference center. CF NBS is not full proof: some diagnoses will be missed and in some babies the diagnosis cannot be confirmed nor ruled out with certainty. Screening algorithms that include gene sequencing will detect a high number of such babies that are screen positive with an inconclusive diagnosis (CFSPID). Even in 2016, the most reliable and widely available diagnostic test for CF is the measurement of chloride concentration in sweat. The method of choice is sweat induction by pilocarpine iontophoresis, followed by sweat collection on a gauze or filter paper or in a Macroduct coil. Since mutation specific therapies have become available, it is important to identify the mutations responsible for CF in each individual patient. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Work disability in adults with cystic fibrosis.

PubMed

Gillen, M; Lallas, D; Brown, C; Yelin, E; Blanc, P

1995-07-01

Greater numbers of persons with cystic fibrosis (CF) reach adulthood and, therefore, actively participate in the labor force. In this study, we estimated labor force participation rates and determined risk factors for work disability among persons with CF. We recruited 49 (73%) of 67 adults followed at one of two hospital-based CF centers. We ascertained employment history and CF-attributed work disability by structured questionnaire. Independently, we reviewed medical records for demographics and illness severity indicators. We analyzed potential risk factors for work disability by logistic regression analysis. All of those studied reported past or present labor force participation, consistent with high work motivation. Complete cessation of work attributed to CF was reported by 17 (35%; 95% CI, 21 to 49%). Although 23 (47%; 95% CI, 32 to 60%) of those surveyed stated that CF had affected career choice, only nine respondents had ever received career counselling and 16 had ever discussed job choice with their physicians. After adjusting for standard measures of disease severity by multiple logistic regression, age, adult diagnosis of CF, female gender, and single marital status, analyzed as a group, provided significant additional explanatory power to a predictive model of disability risk (model chi square [4 d.f.] = 11.5, p < 0.05). Health care professionals who design interventions targeted at work disability among persons with CF should address demographic factors as well as illness severity and should assess the vocational needs of persons with CF and the potential benefit of career counselling.

CF2 Detection in Radio-Frequency Ar/CHF3 Plasmas by Fourier Transform Infrared Spectroscopy

NASA Technical Reports Server (NTRS)

Kim, J. S.; Rao, M. V. V. S.; Cappelli, M. A.; Sharma, S. P.

1999-01-01

CFx radicals, in particular CF2, are instrumental in anisotropic etching of SiO2. In order to optimize the CFx radical population in a given process environment, it is imperative that we understand their production mechanism. Towards this goal, we have conducted a series of quantitative measurements of CF2 radicals in low pressure RF plasmas similar to those used in SiO2 etching. In this study, we present preliminary results for Ar/CHF3 plasmas operating at pressures ranging from 10-50 mTorr and powers ranging from 100-500 W in the GEC reference cell, modified for inductive (transformer) coupling. Fourier transform infrared (FTIR) spectroscop) is used to observe the absorption features of the CF2 radical in the 1114 cm-1 and 1096 cm-1 spectral regions. The FTIR spectrometer is equipped with a high-sensitivity mercury cadmium telluride (MCT) detector and has afixed resolution of 0.125 cm- 1. The CF2 concentrations are measured for a range of operating pressures and discharge power levels, and are compared to measurements of the relative CF2 concentrations made by mass spectrometry using the method of appearance potential for radical selectivity.

Stimulated nitric oxide production and arginine deficiency in children with cystic fibrosis with nutritional failure.

PubMed

Engelen, Mariëlle P K J; Com, Gulnur; Luiking, Yvette C; Deutz, Nicolaas E P

2013-08-01

To determine whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide (NO) production in pediatric patients with cystic fibrosis (CF) and nutritional failure. In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline (Cit), and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. Increased arginine clearance was found in patients with CF (P < .001), whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P < .001), de novo arginine synthesis, and protein breakdown and synthesis (P < .05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n = 7) had significantly higher NO production (P < .05), de novo arginine synthesis, Cit production (P < .001), and plasma Cit concentration (P < .05) and lower plasma arginine concentration (P < .05) than those without nutritional failure (n = 9). Nutritional failure in CF is associated with increased NO production. However, up-regulation of de novo arginine synthesis and Cit production was not sufficient to meet the increased arginine needs leading to arginine deficiency. Copyright © 2013 Mosby, Inc. All rights reserved.

Quantum cascade laser based monitoring of CF{sub 2} radical concentration as a diagnostic tool of dielectric etching plasma processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hübner, M.; Lang, N.; Röpcke, J.

2015-01-19

Dielectric etching plasma processes for modern interlevel dielectrics become more and more complex by the introduction of new ultra low-k dielectrics. One challenge is the minimization of sidewall damage, while etching ultra low-k porous SiCOH by fluorocarbon plasmas. The optimization of this process requires a deeper understanding of the concentration of the CF{sub 2} radical, which acts as precursor in the polymerization of the etch sample surfaces. In an industrial dielectric etching plasma reactor, the CF{sub 2} radical was measured in situ using a continuous wave quantum cascade laser (cw-QCL) around 1106.2 cm{sup −1}. We measured Doppler-resolved ro-vibrational absorption lines andmore » determined absolute densities using transitions in the ν{sub 3} fundamental band of CF{sub 2} with the aid of an improved simulation of the line strengths. We found that the CF{sub 2} radical concentration during the etching plasma process directly correlates to the layer structure of the etched wafer. Hence, this correlation can serve as a diagnostic tool of dielectric etching plasma processes. Applying QCL based absorption spectroscopy opens up the way for advanced process monitoring and etching controlling in semiconductor manufacturing.« less

Regions of the Cf-9B disease resistance protein able to cause spontaneous necrosis in Nicotiana benthamiana lie within the region controlling pathogen recognition in tomato.

PubMed

Chakrabarti, Apratim; Panter, Stephen N; Harrison, Kate; Jones, Jonathan D G; Jones, David A

2009-10-01

The tomato Cf-9 and Cf-9B genes both confer resistance to the leaf mold fungus Cladosporium fulvum but only Cf-9 confers seedling resistance and recognizes the avirulence (Avr) protein Avr9 produced by C. fulvum. Using domain swaps, leucine-rich repeats (LRR) 5 to 15 of Cf-9 were shown to be required for Cf-9-specific resistance to C. fulvum in tomato, and the entire N-terminus up to LRR15 of Cf-9B was shown to be required for Cf-9B-specific resistance. Finer domain swaps showed that nine amino-acid differences in LRR 13 to 15 provided sufficient Cf-9-specific residues in a Cf-9B context for recognition of Avr9 in Nicotiana tabacum or sufficient Cf-9B residues in a Cf-9 context for a novel necrotic response caused by the expression of Cf-9B in N. benthamiana. The responses conferred by LRR 13 to 15 were enhanced by addition of LRR 10 to 12, and either region of Cf-9B was found to cause necrosis in N. benthamiana when the other was replaced by Cf-9 sequence in a Cf-9B context. As a consequence, the domain swap with LRR 13 to 15 of Cf-9 in a Cf-9B context gained the dual ability to recognize Avr9 and cause necrosis in N. benthamiana. Intriguingly, two Cf-9B-specific domain swaps gave differing results for necrosis assays in N. benthamiana compared with disease resistance assays in transgenic tomato. The different domain requirements in these two cases suggest that the two assays detect unrelated ligands or detect related ligands in slightly different ways. A heat-sensitive necrosis-inducing factor present in N. benthamiana intercellular washing fluids was found to cause a necrotic response in N. tabacum plants carrying Hcr9-9A, Cf-9B, and Cf-9 but not in plants carrying only Cf-9. We postulate that this necrosis-inducing factor is recognized by Cf-9B either directly as a ligand or indirectly as a regulator of Cf-9B autoactivity.

A Targeted Q-PCR-Based Method for Point Mutation Testing by Analyzing Circulating DNA for Cancer Management Care.

PubMed

Thierry, Alain R

2016-01-01

Circulating cell-free DNA (cfDNA) is a valuable source of tumor material available with a simple blood sampling enabling a noninvasive quantitative and qualitative analysis of the tumor genome. cfDNA is released by tumor cells and exhibits the genetic and epigenetic alterations of the tumor of origin. Circulating cell-free DNA (cfDNA) analysis constitutes a hopeful approach to provide a noninvasive tumor molecular test for cancer patients. Based upon basic research on the origin and structure of cfDNA, new information on circulating cell-free DNA (cfDNA) structure, and specific determination of cfDNA fragmentation and size, we revisited Q-PCR-based method and recently developed a the allele-specific-Q-PCR-based method with blocker (termed as Intplex) which is the first multiplexed test for cfDNA. This technique, named Intplex(®) and based on a refined Q-PCR method, derived from critical observations made on the specific structure and size of cfDNA. It enables the simultaneous determination of five parameters: the cfDNA total concentration, the presence of a previously known point mutation, the mutant (tumor) cfDNA concentration (ctDNA), the proportion of mutant cfDNA, and the cfDNA fragmentation index. Intplex(®) has enabled the first clinical validation of ctDNA analysis in oncology by detecting KRAS and BRAF point mutations in mCRC patients and has demonstrated that a blood test could replace tumor section analysis for the detection of KRAS and BRAF mutations. The Intplex(®) test can be adapted to all mutations, genes, or cancers and enables rapid, highly sensitive, cost-effective, and repetitive analysis. As regards to the determination of mutations on cfDNA Intplex(®) is limited to the mutational status of known hotspot mutation; it is a "targeted approach." However, it offers the opportunity in detecting quantitatively and dynamically mutation and could constitute a noninvasive attractive tool potentially allowing diagnosis, prognosis, theranostics, therapeutic monitoring, and follow-up of cancer patients expanding the scope of personalized cancer medicine.

A novel method for blood volume estimation using trivalent chromium in rabbit models.

PubMed

Baby, Prathap Moothamadathil; Kumar, Pramod; Kumar, Rajesh; Jacob, Sanu S; Rawat, Dinesh; Binu, V S; Karun, Kalesh M

2014-05-01

Blood volume measurement though important in management of critically ill-patients is not routinely estimated in clinical practice owing to labour intensive, intricate and time consuming nature of existing methods. The aim was to compare blood volume estimations using trivalent chromium [(51)Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). Blood volume estimation in 33 rabbits was carried out using EBD method and concentration determined using spectrophotometric assay followed by blood volume estimation using direct injection of (51)Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using (51)Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using (51)Cr(III). The mean circulating blood volume of 33 rabbits using EBD was 142.02 ± 22.77 ml or 65.76 ± 9.31 ml/kg and using (51)Cr(III) was estimated to be 195.66 ± 47.30 ml or 89.81 ± 17.88 ml/kg. The CF was found to be 0.77. The mean blood volume of 13 rabbits measured using EBD was 139.54 ± 27.19 ml or 66.33 ± 8.26 ml/kg and using (51)Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). The estimation of blood volume using (51)Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using (51)Cr(III) to find its application in acute clinical settings.

An exploration of the experience of compassion fatigue in clinical oncology nurses.

PubMed

Perry, Beth; Toffner, Greg; Merrick, Trish; Dalton, Janice

2011-01-01

Compassion fatigue (CF) is "debilitating weariness brought about by repetitive, empathic responses to the pain and suffering of others" (LaRowe, 2005, p. 21). The work performed by oncology nurses, and the experiences of the people they care for, place oncology nurses at high risk for CF (Pierce et al., 2007; Ferrell & Coyle, 2008). Thus oncology nurses were chosen as the study focus. This paper details a descriptive exploratory qualitative research study that investigated the experience of CF in Canadian clinical oncology registered nurses (RNs). A conceptual stress process model by Aneshensel, Pearlin, Mullan, Zarit, and Whitlatch (1995) that considers caregivers' stress in four domains provided the study framework (see Figure 1). Nineteen study participants were recruited through an advertisement in the Canadian Oncology Nursing Journal (CONJ). The advertisement directed potential participants to a university-based online website developed for this study. Participants completed a questionnaire and wrote a narrative describing an experience with CF and submitted these through the secure research website. Data were analyzed thematically. Five themes include: defining CF, causes of CF, factors that worsen CF, factors that lessen CF, and outcomes of CF. Participants had limited knowledge about CF, about lack of external support, and that insufficient time to provide high quality, care may precipitate CF. The gap between quality of care nurses wanted to provide and what they were able to do, compounded by coexisting physical and emotional stress, worsened CF. CF was lessened by colleague support, work-life balance, connecting with others, acknowledgement, and maturity and experience. Outcomes of CF included profound fatigue of mind and body, negative effects on personal relationships, and considering leaving the specialty. Recommendations that may enhance oncology nurse well-being are provided.

In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies.

PubMed

McGarry, Meghan E; Illek, Beate; Ly, Ngoc P; Zlock, Lorna; Olshansky, Sabrina; Moreno, Courtney; Finkbeiner, Walter E; Nielson, Dennis W

2017-04-01

Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, decreases sweat chloride concentration, and improves pulmonary function in 6% of cystic fibrosis (CF) patients with specific CFTR mutations. Ivacaftor increases chloride transport in many other CFTR mutations in non-human cells, if CFTR is in the epithelium. Some CF patients have CFTR in the epithelium with residual CFTR function. The effect of ivacaftor in these patients is unknown. This was a series of randomized, crossover N-of-1 trials of ivacaftor and placebo in CF patients ≥8 years old with potential residual CFTR function (intermediate sweat chloride concentration, pancreatic sufficient, or mild bronchiectasis on chest CT). Human nasal epithelium (HNE) was obtained via nasal brushing and cultured. Sweat chloride concentration change was the in vivo outcome. Chloride current change in HNE cultures with ivacaftor was the in vitro outcome. Three subjects had decreased sweat chloride concentration (-14.8 to -40.8 mmol/L, P < 0.01). Two subjects had unchanged sweat chloride concentration. Two subjects had increased sweat chloride concentration (+23.8 and +27.3 mmol/L, P < 0.001); both were heterozygous for A455E and pancreatic sufficient. Only subjects with decreased sweat chloride concentration had increased chloride current in HNE cultures. Some CF patients with residual CFTR function have decreased sweat chloride concentration with ivacaftor. Increased chloride current in HNE cultures among subjects with decreased sweat chloride concentrations may predict clinical response to ivacaftor. Ivacaftor can increase sweat chloride concentration in certain mutations with unclear clinical effect. Pediatr Pulmonol. 2017;52:472-479. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Attitudes and Decision Making Related to Pregnancy Among Young Women with Cystic Fibrosis.

PubMed

Kazmerski, Traci M; Gmelin, Theresa; Slocum, Breonna; Borrero, Sonya; Miller, Elizabeth

2017-04-01

Introduction The number of female patients with CF able to consider pregnancy has increased with improved therapies. This study explored attitudes and decision making regarding pregnancy among young women with CF. Methods Twenty-two women with CF ages 18-30 years completed semi-structured, in-person interviews exploring experiences with preconception counseling and reproductive care in the CF setting. Interviews were audio-recorded, transcribed, and coded using a thematic analysis approach. Results Participants indicated CF is a major factor in pregnancy decision making. Although women acknowledged that CF influences attitudes toward pregnancy, many expressed confusion about how CF can affect fertility/pregnancy. Many perceived disapproval from CF providers regarding pregnancy and were dissatisfied with reproductive care in the CF setting. Discussion Young female patients with CF reported poor understanding of the effect of CF on fertility and pregnancy and limited preconception counseling in CF care. Improvements in female sexual and reproductive health care in CF are warranted.

Atmospheric perfluorocarbons.

PubMed

Aslam, M; Khalil, K; Rasmussen, Reinhold A; Culbertson, John A; Prins, John M; Grimsrud, Eric P; Shearer, Martha J

2003-10-01

Collectively, man-made emissions of a few greenhouse gases may cause about the same amount of global warming as increasing carbon dioxide. Among the most potent of these non-CO2 greenhouse gases are the perfluorocarbons that have extraordinarily long atmospheric lifetimes of 10,000 to more than 50,000 yr. We report atmospheric concentrations over two decades, between 1978 and 1997, of the three most abundant perfluorocarbons--CF4, C2F6, and C3F8--and delineate the sources that account for the present abundances and trends. We show that C2F6 and C3F8 are present at only 2.9 and 0.2 pptv, respectively. CF4 is the most abundant perfluorocarbon at 74 pptv (in 1997) of which about 40 pptv are from natural emissions, 33 pptv from aluminum manufacturing, and 1 pptv from the semiconductor industry. The increasing trend of CF4 has slowed in recent years due to the major reductions in the emission rate per ton of aluminum produced. The effect of the falling emission factor is partially offset by increased production and increasing use by the semiconductor industry.

Calibration-free wavelength-modulation spectroscopy based on a swiftly determined wavelength-modulation frequency response function of a DFB laser.

PubMed

Zhao, Gang; Tan, Wei; Hou, Jiajia; Qiu, Xiaodong; Ma, Weiguang; Li, Zhixin; Dong, Lei; Zhang, Lei; Yin, Wangbao; Xiao, Liantuan; Axner, Ove; Jia, Suotang

2016-01-25

A methodology for calibration-free wavelength modulation spectroscopy (CF-WMS) that is based upon an extensive empirical description of the wavelength-modulation frequency response (WMFR) of DFB laser is presented. An assessment of the WMFR of a DFB laser by the use of an etalon confirms that it consists of two parts: a 1st harmonic component with an amplitude that is linear with the sweep and a nonlinear 2nd harmonic component with a constant amplitude. Simulations show that, among the various factors that affect the line shape of a background-subtracted peak-normalized 2f signal, such as concentration, phase shifts between intensity modulation and frequency modulation, and WMFR, only the last factor has a decisive impact. Based on this and to avoid the impractical use of an etalon, a novel method to pre-determine the parameters of the WMFR by fitting to a background-subtracted peak-normalized 2f signal has been developed. The accuracy of the new scheme to determine the WMFR is demonstrated and compared with that of conventional methods in CF-WMS by detection of trace acetylene. The results show that the new method provides a four times smaller fitting error than the conventional methods and retrieves concentration more accurately.

Relation between different metal pollution criteria in sediments and its contribution on assessing toxicity.

PubMed

Alves, Cristina M; Ferreira, Carlos M H; Soares, Helena M V M

2018-05-14

Several tools have been developed and applied to evaluate the metal pollution status of sediments and predict their potential ecological risk assessment. To date, a comprehensive relationship between the information given by these sediment tools for predicting metal bioavailability and the effective toxicity observed is lacking. In this work, the possible inter-correlations between the data outcoming from using several qualitative evaluation tools of the sediment contamination (contamination factor, CF, the enrichment factor, EF, or the geoaccumulation index, Igeo), metal speciation on sediments (evaluated by the modified BCR sequential extraction procedure) and free metal concentrations in pore waters were studied. It was also our aim to evaluate if these assessment tools could be used for predicting the pore waters toxicity data as toxicity proxy. Principal component analysis and cluster analysis revealed that two quality indices used (CF and EF) were highly correlatable with the more labile fractions from BCR sediment speciation. However, neither of these parameters did correlate with the toxicity of pore waters measured by the chronic toxicity (72 h) in Pseudokirchneriella subcapitata. In contrast, the toxic effects of the given total metal load in sediments were better evaluated by using an additive metal approach using pore water free metal concentrations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Growth assessment and risk factors of malnutrition in children with cystic fibrosis

PubMed Central

Isa, Hasan M.; Al-Ali, Lina F.; Mohamed, Afaf M.

2016-01-01

Objectives: To evaluate the nutritional status, to screen for the presence of malnutrition, and to study the possible risk factors associated with malnutrition in patients with cystic fibrosis (CF). Methods: A retrospective cross-sectional review of medical records of all diagnosed CF patients in the Pediatric Department, Salmaniya Medical Complex, Manama, Kingdom of Bahrain, between January 1984 and May 2015 was conducted. Demographic and anthropometric data were collected from records of last visit to CF clinic. Nutritional status and risk factors of malnutrition were assessed. Results: All records of 109 CF patients were reviewed. Forty-seven pediatric patients were included in the study. All included patients were on pancreatic enzyme replacement and 42 (89%) received high-calorie supplementation. Growth failure was noted in 34 (72%) patients, 19 (56%) were wasted and stunted, 8 (23.5%) were wasted only, and 7 (20.5%) were stunted. Low birth weight (p=0.032), and the presence of gastroesophageal reflux disease (GERD) (p=0.039) were the significant risk factors for malnutrition. Conclusion: Most CF patients in Bahrain (72%) are malnourished. Low birth weight and the presence of GERD are risk factors. PMID:26905352

Aerobic and heterotrophic nitrogen removal by Enterobacter cloacae CF-S27 with efficient utilization of hydroxylamine.

PubMed

Padhi, Soumesh Kumar; Tripathy, Swetaleena; Mohanty, Sriprakash; Maiti, Nikhil Kumar

2017-05-01

Heterotrophic bacterium, Enterobacter cloacae CF-S27 exhibited simultaneous nitrification and aerobic denitrification in presence of high concentration of hydroxylamine. With the initial nitrogen concentration of 100mgL -1 h -1 , ammonium, nitrate and nitrite removal efficiencies were 81%, 99.9% and 92.8%, while the corresponding maximum removal rates reached as high as 11.6, 15.1 and 11.2mgL -1 h -1 respectively. Quantitative amplification by real time PCR and enzyme assay demonstrated that hydroxylamine reductase gene (hao) is actively involved in hetrotrophic nitrification and aerobic denitrification process of Enterobacter cloacae CF-S27. PCR primers were designed targeting amplification of hao gene from diversified environmental soil DNA. The strain Enterobacter cloacae CF-S27 significantly maintained the undetectable amount of dissolved nitrogen throughout 60days of zero water exchange fish culture experiment in domestic wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experimental ion mobility measurements for the LCTPC collaboration—Ar-CF4 mixtures

NASA Astrophysics Data System (ADS)

Santos, M. A. G.; Kaja, M. A.; Cortez, A. F. V.; Veenhof, R.; Neves, P. N. B.; Santos, F. P.; Borges, F. I. G. M.; Conde, C. A. N.

2018-04-01

In this paper we present the results of the ion mobility measurements made in pure carbon tetrafluoride (CF4) and gaseous mixtures of argon with carbon tetrafluoride (Ar-CF4) for pressures ranging from 6 to 10 Torr (8–10.6 mbar) and for low reduced electric fields in the 10 Td to 25 Td range (2.4-6.1 kVṡcm‑1ṡbar‑1), at room temperature. The time of arrival spectra revealed only one peak throughout the entire range studied which was attributed to CF3+. However, for Ar concentrations above 70%, a bump starts to appear at the left side of the main peak for reduced electric fields higher than 15 Td, which was attributed to impurities. The reduced mobilities obtained from the peak centroid of the time-of-arrival spectra are presented for Ar concentrations in the 5%–95% range.

Hydrogen cyanide as a biomarker for Pseudomonas aeruginosa in the breath of children with cystic fibrosis.

PubMed

Enderby, Beth; Smith, David; Carroll, W; Lenney, W

2009-02-01

Hydrogen cyanide (HCN) is emitted by Pseudomonas aeruginosa (PA) in vitro. We hypothesized that exhaled HCN could be measured using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) and that concentrations would be higher in children with cystic fibrosis (CF) and PA infection than in children with asthma. Children aged 7-17 years with CF (n = 16) or asthma (n = 21) attending outpatient clinics provided breath samples between July and December 2007. HCN was measured using the SIFT-MS Profile 3 instrument. FeNO was measured with a Sievers NOA 280i analyzer. Baseline inter-group differences between HCN and FeNO concentrations were compared using the Mann-Whitney U test. Children were invited to re-attend fortnightly. Breath samples, spirometry, growth and clinical status were measured at each visit. There were significant baseline differences in exhaled HCN and FeNO concentrations between the two groups. Children with CF had higher median HCN concentrations than those with asthma: 13.5 parts per billion (ppb) (IQR 8.1-16.5) versus 2.0 ppb (IQR 0.0-4.8) (P < 0.001). Children with CF had lower median FeNO levels compared to children with asthma: 13.4 ppb (IQR 8.9-17.6) versus 57.9 ppb (IQR 34.0-85.7) (P < 0.001). Intra-subject variability was high and significant changes in HCN concentrations were not observed related to changes in lung function or clinical status. This study provides proof of principle that HCN is detectable in the breath of children with CF and is elevated compared to children with asthma. Further studies are required to capture data from acutely unwell children and more accurately delineate responses to treatment. (c) 2009 Wiley-Liss, Inc.

An Open-Label Investigation of the Pharmacokinetics and Tolerability of Oral Cysteamine in Adults with Cystic Fibrosis.

PubMed

Devereux, Graham; Steele, Sandra; Griffiths, Kairen; Devlin, Edward; Fraser-Pitt, Douglas; Cotton, Seonaidh; Norrie, John; Chrystyn, Henry; O'Neil, Deborah

2016-08-01

Cysteamine is licensed for use in nephropathic cystinosis but preclinical data suggest a role in managing cystic fibrosis (CF). This study aimed to determine whether oral cysteamine is absorbed in adult CF patients and enters the bronchial secretions. Tolerability outcomes were also explored. Patients ≥18 years of age, weighing >50 kg with stable CF lung disease were commenced on oral cysteamine bitartrate (Cystagon(®)) 450 mg once daily, increased weekly to 450 mg four times daily. Serial plasma cysteamine concentrations were measured for 24 h after the first dose. Participants were reviewed every week for 6 weeks, except at 4 weeks. Plasma cysteamine concentrations were measured 8 h after dosing when reviewed at 1, 2 and 3 weeks and 6 h after dosing when reviewed at 5 weeks. Sputum cysteamine concentration was also quantified at the 5-week assessment. Seven of the ten participants reported adverse reactions typical of cysteamine, two participants discontinued intervention. Following the first 450-mg dose, mean (SD) maximum concentration (C max) was 2.86 (1.96) mg/l, the time corresponding to C max (T max) was 1.2 (0.7) h, the half-life (t ½) was 3.7 (1.7) h, clearance (CL/F) 89.9 (30.5) L/h and volume of distribution (V d/F) 427 (129) L. Cysteamine appeared to accumulate in sputum with a median (interquartile range) sputum:plasma cysteamine concentration ratio of 4.2 (0.98-8.84). Oral cysteamine is absorbed and enters the bronchial secretions in patients with CF. Although adverse reactions were common, the majority of patients continued with cysteamine. Further trials are required to establish the risk benefit ratio of cysteamine therapy in CF.

The Incidence of Hypogonadotropic Hypogonadism in Type 2 Diabetic Men in Polish Population

PubMed Central

Rabijewski, Michał; Zgliczyński, Wojciech; Piątkiewicz, Paweł

2013-01-01

The aim of this study was to investigate the incidence of hypogonadotropic hypogonadism (HH) in type 2 diabetic men (T2DM) in population of Polish men and examine the possible influence of estradiol levels and glycemic control. We evaluated TT, cfT, estradiol, and glycemic control (HbA1c) in 184 diabetic men and in 149 nondiabetic control group. The mean HbA1c was 8.6 ± 0.2% and 6.1 ± 0.3% and cfT concentration was 0.315 ± 0.08 nmol/L and 0.382 ± 0.07 nmol/L, respectively. T2DM had higher E2 concentration than nonobese control men (29.4 ± 3.7 pg/mL versus 24.5 ± 2.9 pg/mL). Forty-six percent of T2DM were hypogonadal and 93% had HH. We observed inverse relationship between BMI and cfT (r = −0.341, P < 0.01) and positive between BMI and E2 (r = 0.329, P < 0.01). E2 concentration was higher in T2DM with HH versus T2DM with normal TT/cfT concentration (34.5 ± 5.2 versus 27.4 ± 3.4 pg/mL). We observed negative correlation between HbA1c and cfT (r = −0.336, P < 0.005) but positive between HbA1c and E2 levels (r = 0.337, P < 0.002). The prevalence of obesity, hypertension, and CVD was higher in men with hypogonadism. High incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population is associated with poor glycemic control and can be secondary to an increase in estradiol concentrations. PMID:24222915

Maternal cfDNA screening for Down syndrome--a cost sensitivity analysis.

PubMed

Cuckle, Howard; Benn, Peter; Pergament, Eugene

2013-07-01

This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening. A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta-analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection. The main factor was the unit cost of cfDNA testing. For example, replacing a combined test costing $150 with 3% false-positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when replacing a quadruple test and higher for a 5% false-positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10% to 20% women were selected for cfDNA testing by conventional screening was considerably more cost-efficient. Costs were sensitive to cfDNA uptake. Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs fall substantially. Until this happens, the contingent use of cfDNA is recommended. © 2013 John Wiley & Sons, Ltd.

The role and diagnostic value of cell-free DNA in systemic lupus erythematosus.

PubMed

Truszewska, Anna; Foroncewicz, Bartosz; Pączek, Leszek

2017-01-01

Cell-free DNA (cfDNA) represents a small fraction of total DNA pool that circulates freely in the blood both in normal and pathological conditions. Data indicate that cfDNA plays an important role in the pathogenesis of systemic lupus erythematosus (SLE) and hypomethylation may be crucial for its immunogenic properties. Although differences in quantification methodology hinder the comparison of results between the studies, it appears that levels of cfDNA are abnormally elevated in SLE patients and correlate with various antibody titers, but not with disease activity. Increased cfDNA concentration, however, may be associated with active lupus nephritis. Most of the studies confirmed apoptosis as the major cfDNA release mechanism in various conditions, but formation of neutrophil extracellular traps may significantly contribute to the cfDNA generation in SLE patients. In this review, we summarise current knowledge about the role and possible origin of cfDNA in SLE patients, and discuss why cfDNA testing for diagnostic and prognosis of SLE remains questionable.

Spatial Resolution Effects of Digital Terrain Models on Landslide Susceptibility Analysis

NASA Astrophysics Data System (ADS)

Chang, K. T.; Dou, J.; Chang, Y.; Kuo, C. P.; Xu, K. M.; Liu, J. K.

2016-06-01

The purposes of this study are to identify the maximum number of correlated factors for landslide susceptibility mapping and to evaluate landslide susceptibility at Sihjhong river catchment in the southern Taiwan, integrating two techniques, namely certainty factor (CF) and artificial neural network (ANN). The landslide inventory data of the Central Geological Survey (CGS, MOEA) in 2004-2014 and two digital elevation model (DEM) datasets including a 5-meter LiDAR DEM and a 30-meter Aster DEM were prepared. We collected thirteen possible landslide-conditioning factors. Considering the multi-collinearity and factor redundancy, we applied the CF approach to optimize these thirteen conditioning factors. We hypothesize that if the CF values of the thematic factor layers are positive, it implies that these conditioning factors have a positive relationship with the landslide occurrence. Therefore, based on this assumption and positive CF values, seven conditioning factors including slope angle, slope aspect, elevation, terrain roughness index (TRI), terrain position index (TPI), total curvature, and lithology have been selected for further analysis. The results showed that the optimized-factors model provides a better accuracy for predicting landslide susceptibility in the study area. In conclusion, the optimized-factors model is suggested for selecting relative factors of landslide occurrence.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

PubMed

Gaitch, Natacha; Hubert, Dominique; Gameiro, Christine; Burgel, Pierre-Régis; Houriez, Florence; Martinez, Brigitte; Honoré, Isabelle; Chapron, Jeanne; Kanaan, Reem; Dusser, Daniel; Girodon, Emmanuelle; Bienvenu, Thierry

2016-01-01

Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown. Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded. 19 experienced at least one episode of acute pancreatitis (AP) (AP+) and 40 patients did not (AP-). No influence of environmental factor was evidenced. No specific CFTR genotype was found predictive of pancreatitis. Patients sharing the same CFTR genotype may or may not experience AP episodes. Frequent and rare missense variants were found in 78.9% patients in group AP+ and 67.5% in group AP- but a few of them were pathogenic. AP or recurrent AP (RAP) is a frequent complication in our series of adult CF-PS patients. The majority of mild CFTR mutations found in group AP+ were located in the first transmembrane region. No clear other genetic factor could be found predictive of AP/RAP. Further experiments in large homogenous cohorts of CF-PS patients, including whole genome sequencing, may identify genetic predisposing factors to pancreatitis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

A novel device for quantitative measurement of chloride concentration by fluorescence indicator

NASA Astrophysics Data System (ADS)

Wang, Junsheng; Wu, Xudong; Chon, Chanhee; Gonska, Tanja; Li, Dongqing

2012-02-01

Cystic fibrosis (CF) is a life-threatening genetic disease. At present, the common method for diagnosis of CF is to detect the chloride concentration in sweat using ion-selective electrodes. However, the current sweat testing methods require a relatively large quantity of sweat sample, at least 25 µL, which is very difficult to obtain, especially for newborns. This paper presents a new method and a new device for rapid detection of the chloride concentration from a small volume of solution. In this method, the chloride concentration is determined quantitatively by the fluorescence intensity of MQAE, a chloride ion fluorescent indicator. In this device, the sample is carried by a small piece of filter paper on a cover glass exposed to an UV LED light source. The resulting fluorescent signals are detected by a Si photodiode. Data acquisition and processing are accomplished by LabVIEW software in a PDA. Based on the Stern-Volmer relationship, the effects of different parameters on the fluorescence intensity were analyzed. The observed significant difference between 40 and 60 mM (the borderline of chloride concentration for CF) is discussed in this paper. The results show that detection can be completed within 10 s. The minimum detectable volume of the chloride solution is 1 μL. The novel method and the device are of great potential for CF diagnosis.

Rate constants and temperature dependences for the reactions of hydroxyl radical with several halogenated methanes, ethanes, and propanes by relative rate measurements

NASA Technical Reports Server (NTRS)

Hsu, K.-J.; DeMore, W. B.

1995-01-01

Rate constants of 15 OH reactions with halogen-substituted alkanes, C1 to C3, were studied using a relative rate technique in the temperature range 283-403 K. Compounds studied were CHF2Cl (22), CHF2Br (22B), CH3F (41), CH2F2 (32), CHF3 (23), CHClFCCl2F (122a), CHCl2CF3 (123), CHClFCF3 (124), CH3CF3 (143a), CH3CH2F (161), CF3CHFCF3 (227ea), CF3CH2CF3 (236fa), CF3CHFCHF2 (236ea), and CHF2CF2CH2F (245ca). Using CH4, CH3CCl3, CF3CF2H, and C2H6 as primary reference standards (JPL 92-20 rate constants), absolute rate constants are derived. Results are in good agreement with previous experimental results for six of the compounds studied, including CHF2Cl, CHF2Br, CH2F2, CH3CF3, CHFClCFCl2, and CF3CHFCF3. For the remainder the relative rate constants are lower than those derived from experiments in which OH loss was used to measure the reaction rate. Comparisons of the derived Arrhenius A factors with previous literature transition-state calculations show order of magnitude agreement in most cases. However, the experimental A factors show a much closer proportionality to the number of H atoms in the molecule than is evident from the transition state calculations. For most of the compounds studied, an A factor of (8 +/- 3)E-13 cm(exp 3)/(molecule s) per C-H bond is observed. A new measurement of the ratio k(CH3CCl3)/k(CH4) is reported that is in good agreement with previous data.

Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

PubMed Central

Troia, Roberta; Giunti, Massimo; Calipa, Stefano; Goggs, Robert

2018-01-01

Canine gastric dilatation–volvulus (GDV) is a life-threatening disease characterized by extensive tissue ischemia, tissue hypoperfusion, and systemic inflammation. Biomarkers that better reflect the severity of gastric necrosis and systemic inflammation would aid clinicians in the management of these patients. This study aimed to investigate the prognostic significance of cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), and procalcitonin (PCT) in dogs with GDV. Concentrations of cfDNA, HMGB1, and PCT were measured in citrated plasma samples collected from 29 dogs with GDV at hospital admission. Additional data collected included baseline lactate concentrations, APPLEfast score, evidence of gastric necrosis, occurrence of postoperative complications, and outcome. Twenty-four healthy dogs were sampled as controls. Continuous variables between groups were compared with the Mann–Whitney U and correlations between continuous variables were assessed by calculation of Spearman’s correlation coefficient. Alpha was set at 0.05. Dogs with GDV had significantly greater concentrations of cfDNA, HMGB1, and PCT compared to controls (P = 0.0009, P = 0.004, and P = 0.009, respectively). PCT concentrations were significantly higher in non-survivors compared to survivors (P = 0.008). Dogs with gastric necrosis had significantly greater lactate concentrations compared to dogs without gastric necrosis (P = 0.0005). The APPLEfast score was not prognostic. Lactate and PCT concentrations were moderately, positively correlated (rs 0.51, P = 0.0005). Concentrations of the inflammatory biomarkers cfDNA, HMGB1, and PCT are increased in canine GDV. Only lactate and PCT concentrations were prognostic in this population of GDV dogs and were predictive of the presence of gastric necrosis and of non-survival to hospital discharge, respectively. PMID:29686994

Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation-Volvulus Syndrome.

PubMed

Troia, Roberta; Giunti, Massimo; Calipa, Stefano; Goggs, Robert

2018-01-01

Canine gastric dilatation-volvulus (GDV) is a life-threatening disease characterized by extensive tissue ischemia, tissue hypoperfusion, and systemic inflammation. Biomarkers that better reflect the severity of gastric necrosis and systemic inflammation would aid clinicians in the management of these patients. This study aimed to investigate the prognostic significance of cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), and procalcitonin (PCT) in dogs with GDV. Concentrations of cfDNA, HMGB1, and PCT were measured in citrated plasma samples collected from 29 dogs with GDV at hospital admission. Additional data collected included baseline lactate concentrations, APPLE fast score, evidence of gastric necrosis, occurrence of postoperative complications, and outcome. Twenty-four healthy dogs were sampled as controls. Continuous variables between groups were compared with the Mann-Whitney U and correlations between continuous variables were assessed by calculation of Spearman's correlation coefficient. Alpha was set at 0.05. Dogs with GDV had significantly greater concentrations of cfDNA, HMGB1, and PCT compared to controls ( P  = 0.0009, P  = 0.004, and P  = 0.009, respectively). PCT concentrations were significantly higher in non-survivors compared to survivors ( P  = 0.008). Dogs with gastric necrosis had significantly greater lactate concentrations compared to dogs without gastric necrosis ( P  = 0.0005). The APPLE fast score was not prognostic. Lactate and PCT concentrations were moderately, positively correlated ( r s 0.51, P  = 0.0005). Concentrations of the inflammatory biomarkers cfDNA, HMGB1, and PCT are increased in canine GDV. Only lactate and PCT concentrations were prognostic in this population of GDV dogs and were predictive of the presence of gastric necrosis and of non-survival to hospital discharge, respectively.

In vitro activity of levofloxacin against planktonic and biofilm Stenotrophomonas maltophilia lifestyles under conditions relevant to pulmonary infection in cystic fibrosis, and relationship with SmeDEF multidrug efflux pump expression.

PubMed

Pompilio, Arianna; Crocetta, Valentina; Verginelli, Fabio; Di Bonaventura, Giovanni

2016-07-01

The activity of levofloxacin against planktonic and biofilm Stenotrophomonas maltophilia cells and the role played by the multidrug efflux pump SmeDEF were evaluated under conditions relevant to the cystic fibrosis (CF) lung. MIC, MBC and MBEC of levofloxacin were assessed, against five CF strains, under 'standard' (CLSI-recommended) and 'CF-like' (pH 6.8, 5% CO2, in a synthetic CF sputum) conditions. Levofloxacin was tested against biofilms at concentrations (10, 50 and 100 μg mL(-1)) corresponding to achievable serum levels and sputum levels by aerosolisation. smeD expression was evaluated, under both conditions, in planktonic and biofilm cells by RT-PCR. The bactericidal effect of levofloxacin was decreased, in three out of five strains tested, under 'CF-like' conditions (MBC: 2-4 vs 8-16 μg mL(-1), under 'standard' and 'CF-like' conditions, respectively). Biofilm was intrinsically resistant to levofloxacin, regardless of conditions tested (MBECs ≥ 100 μg mL(-1) for all strains). Only under 'CF-like' conditions, smeD expression increased during planktonic-to-biofilm transition, and in biofilm cells compared to stationary planktonic cells. Our findings confirmed that S. maltophilia biofilm is intrinsically resistant to therapeutic concentrations of levofloxacin. Under conditions relevant to CF, smeD overexpression could contribute to levofloxacin resistance. Further studies are warranted to define the clinical relevance of our findings. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Downregulation of the Cl-/HCO3-Exchanger Pendrin in Kidneys of Mice with Cystic Fibrosis: Role in the Pathogenesis of Metabolic Alkalosis.

PubMed

Varasteh Kia, Mujan; Barone, Sharon; McDonough, Alicia A; Zahedi, Kamyar; Xu, Jie; Soleimani, Manoocher

2018-01-01

Patients with cystic fibrosis (CF) are prone to the development of metabolic alkalosis; however, the pathogenesis of this life threatening derangement remains unknown. We hypothesized that altered acid base transport machinery in the kidney collecting duct underlies the mechanism of impaired bicarbonate elimination in the CF kidney. Balance studies in metabolic cages were performed in WT and CFTR knockout (CF) mice with the intestinal rescue in response to bicarbonate loading or salt restriction, and the expression levels and cellular distribution of acid base and electrolyte transporters in the proximal tubule, collecting duct and small intestine were examined by western blots, northern blots and/or immunofluorescence labeling. Baseline parameters, including acid-base and systemic vascular volume status were comparable in WT and CF mice, as determined by blood gas, kidney renin expression and urine chloride excretion. Compared with WT animals, CF mice demonstrated a significantly higher serum HCO3- concentration (22.63 in WT vs. 26.83 mEq/l in CF mice; n=4, p=0.013) and serum pH (7.33 in WT vs. 7.42 in CF mice; n=4, p=0.00792) and exhibited impaired kidney HCO3- excretion (urine pH 8.10 in WT vs. 7.35 in CF mice; n=7, p=0.00990) following a 3-day oral bicarbonate load. When subjected to salt restriction, CF mice developed a significantly higher serum HCO3- concentration vs. WT animals (29.26 mEq/L in CF mice vs. 26.72 in WT; n=5, p=0.0291). Immunofluorescence labeling demonstrated a profound reduction in the apical expression of the Cl-/HCO3- exchanger pendrin in cortical collecting duct cells and western and northern blots indicated diminished plasma membrane abundance and mRNA expression of pendrin in CF kidneys. We propose that patients with cystic fibrosis are prone to the development of metabolic alkalosis secondary to the inactivation of the bicarbonate secreting transporter pendrin, specifically during volume depletion, which is a common occurrence in CF patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Evaluation of the Bronchorelaxant, Genotoxic, and Antigenotoxic Effects of Cassia alata L.

PubMed Central

Ouédraogo, M.; Da, F. L.; Fabré, A.; Konaté, K.; Dibala, C. I.; Carreyre, H.; Thibaudeau, S.; Coustard, J.-M.; Vandebrouck, C.; Bescond, J.; Belemtougri, R. G.

2013-01-01

Aqueous-ethanolic extract of Cassia alata (AECal) and its derived fractions obtained through liquid-liquid fractionation were evaluated for their bronchorelaxant, genotoxic, and antigenotoxic effects. Contractile activity of rats' tracheas in the presence of tested materials, as well as its modifications with different inhibitors and blockers, was isometrically recorded. The antigenotoxic potential of AECal was evaluated on cyclophosphamide- (CP-) induced genotoxicity in the rat. Animals were pretreated with the extract, then liver comet assay was performed. AECal and its chloroformic fractions (CF-AECal) relaxed the contraction induced by Ach, but both were significantly less potent in inhibiting contraction induced by KCl (30 mM; 80 mM). Propranolol, indomethacin, L-NAME, methylene blue, and glibenclamide did not modify the relaxant effect of CF-AECal. TEA altered the response of trachea to CF-AECal. CF-AECal caused a rightward shift without affecting the E max in cumulative concentration-response curves of Ach only at low concentrations. In animals pretreated with the extract, the percentage of CP-induced DNA damage decreased. Our results suggest that (1) muscarinic receptors contribute at least in part to the relaxant effects of CF-AECal; (2) CF-AECal interferes with membrane polarization; and (3) AECal is not genotoxic in vivo and contains chemopreventive phytoconstituents offering protection against CP-induced genotoxicity. PMID:23710211

Ecophysiological capability of Marenzelleria populations inhabiting North Sea estuaries: an overview

NASA Astrophysics Data System (ADS)

Schiedek, Doris

1998-09-01

The metabolic responses of Marenzelleria cf. wireni, a newly established polychaete worm within North Sea estuaries, to various kinds of environmental stress are summarised. With respect to salinity, M. cf. wireni is able to deal with variations within a wide range. In the process of osmotic acclimation, free amino acids are involved. The major amino acid in terms of osmotic effector is glycine, followed by alanine. Under severe hypoxia, M. cf. wireni switches to an anaerobic metabolism, but at a very low oxygen partial pressure (<3 kPa), which indicates efficient utilisation of oxygen. Anaerobic energy production occurs predominantly via the succinate-propionate pathway. When exposed to hydrogen sulphide, M. cf. wireni is able to cope with high sulphide concentrations (up to 3 mmol l-1), but the pattern of end products of the anaerobic energy metabolism changes. In terms of sulphide tolerance, M. cf. wireni probably is even better adapted than other, indigenous polychaetes. However, in comparison with the sibling species Marenzelleria viridis, which appeared at the same time in European waters but mainly inhabits the coastal inlets of the Baltic Sea in high numbers, the metabolic capabilities of M. cf. wireni seem to be more limited at higher sulphide concentrations (>1 mmol l-1). This might have an influence on the distribution pattern of the two sibling species.

Atmospheric chemistry of short-chain haloolefins: photochemical ozone creation potentials (POCPs), global warming potentials (GWPs), and ozone depletion potentials (ODPs).

PubMed

Wallington, T J; Sulbaek Andersen, M P; Nielsen, O J

2015-06-01

Short-chain haloolefins are being introduced as replacements for saturated halocarbons. The unifying chemical feature of haloolefins is the presence of a CC double bond which causes the atmospheric lifetimes to be significantly shorter than for the analogous saturated compounds. We discuss the atmospheric lifetimes, photochemical ozone creation potentials (POCPs), global warming potentials (GWPs), and ozone depletion potentials (ODPs) of haloolefins. The commercially relevant short-chain haloolefins CF3CFCH2 (1234yf), trans-CF3CHCHF (1234ze(Z)), CF3CFCF2 (1216), cis-CF3CHCHCl (1233zd(Z)), and trans-CF3CHCHCl (1233zd(E)) have short atmospheric lifetimes (days to weeks), negligible POCPs, negligible GWPs, and ODPs which do not differ materially from zero. In the concentrations expected in the environment their atmospheric degradation products will have a negligible impact on ecosystems. CF3CFCH2 (1234yf), trans-CF3CHCHF (1234ze(Z)), CF3CFCF2 (1216), cis-CF3CHCHCl (1233zd(Z)), and trans-CF3CHCHCl (1233zd(E)) are environmentally acceptable. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative measurements of mineral elements in milk powders with laser-induced breakdown spectroscopy and inductively coupled plasma atomic emission spectroscopy.

PubMed

Lei, W Q; El Haddad, J; Motto-Ros, V; Gilon-Delepine, N; Stankova, A; Ma, Q L; Bai, X S; Zheng, L J; Zeng, H P; Yu, J

2011-07-01

Mineral elements contained in commercially available milk powders, including seven infant formulae and one adult milk, were analyzed with inductively coupled plasma atomic emission spectrometry (ICP-AES) and laser-induced breakdown spectroscopy (LIBS). The purpose of this work was, through a direct comparison of the analytical results, to provide an assessment of the performance of LIBS, and especially of the procedure of calibration-free LIBS (CF-LIBS), to deal with organic compounds such as milk powders. In our experiments, the matrix effect was clearly observed affecting the analytical results each time laser ablation was employed for sampling. Such effect was in addition directly observed by determining the physical parameters of the plasmas induced on the different samples. The CF-LIBS procedure was implemented to deduce the concentrations of Mg and K with Ca as the internal reference element. Quantitative analytical results with CF-LIBS were validated with ICP-AES measurements and nominal concentrations specified for commercial milks. The obtained good results with the CF-LIBS procedure demonstrate its capacity to take into account the difference in physical parameters of the plasma in the calculation of the concentrations of mineral elements, which allows a significant reduction of the matrix effect related to laser ablation. We finally discuss the way to optimize the implementation of the CF-LIBS procedure for the analysis of mineral elements in organic materials.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan.

PubMed

Dou, Jie; Tien Bui, Dieu; Yunus, Ali P; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan

PubMed Central

Dou, Jie; Tien Bui, Dieu; P. Yunus, Ali; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner. PMID:26214691

Radiocaesium soil-to-wood transfer in commercial willow short rotation coppice on contaminated farm land.

PubMed

Gommers, A; Gäfvert, T; Smolders, E; Merckx, R; Vandenhove, H

2005-01-01

The feasibility of willow short rotation coppice (SRC) for energy production as a revaluation tool for severely radiocaesium-contaminated land was studied. The effects of crop age, clone and soil type on the radiocaesium levels in the wood were assessed following sampling in 14 existing willow SRC fields, planted on radiocaesium-contaminated land in Sweden following Chernobyl deposition. There was only one plot where willow stands of different maturity (R6S2 and R5S4: R, root age and S, shoot age) and clone (Rapp and L78183 both of age category R5S4) were sampled and no significant differences were found. The soils differed among others in clay fraction (3-34%), radiocaesium interception potential (515-6884 meq kg(-1)), soil solution K (0.09-0.95 mM), exchangeable K (0.58-5.77 meq kg(-1)) and cation exchange capacity (31-250 meq kg(-1)). The soil-to-wood transfer factor (TF) of radiocaesium differed significantly between soil types. The TF recorded was generally small (0.00086-0.016 kg kg(-1)), except for willows established on sandy soil (0.19-0.46 kg kg(-1)). Apart from the weak yet significant exponential correlation between the Cs-TF and the solid/liquid distribution coefficient (R2 = 0.54) or the radiocaesium interception potential, RIP (R2 = 0.66), no single significant correlations between soil characteristics and TF were found. The wood-soil solution 137Cs concentration factor (CF) was significantly related to the potassium concentration in the soil solution. A different relation was, however, found between the sandy Trödje soils (CF = 1078.8 x m(K)(-1.83), R2 = 0.99) and the other soils (CF = 35.75 x m(K)(-0.61), R2 =0.61). Differences in the ageing rate of radiocaesium in the soil (hypothesised fraction of bioavailable caesium subjected to fast ageing for Trödje soils only 1% compared to other soils), exchangeable soil K (0.8-1.8 meq kg(-1) for Trödje soils and 1.5-5.8 meq kg(-1) for the other soils) and the ammonium concentration in the soil solution (0.09-0.31 mM NH4+ for the Trödje soils compared to 0.003-0.11 mM NH4+ for the other soils) are put forward as potential factors explaining the higher CF and TF observed for the Trödje soils. Though from the dataset available it was not possible to unequivocally predict the Cs-soil-to-wood-transfer, the generally low TFs observed point to the particular suitability for establishment of SRC on radiocaesium-contaminated land.

External Ballistics. Part 2

DTIC Science & Technology

1978-07-11

ucaymaetrically. Page £98. is a result cf the elastic iroperties cf rccket, of launcher and scil , the initial conditicns of moving the rocket differ from...instrument depends or. many factors: the elastic Fropesties of shaft and gur carriaSe, scil cf the firing position, tallistics of instrument, which

Temporal variation in plankton assemblages and physicochemistry of Devils Lake, North Dakota

USGS Publications Warehouse

Leland, H.V.; Berkas, W.R.

1998-01-01

Seasonal and annual variation in biomass and structure of algal assemblages of hyposaline Devils Lake were examined in relation to turbidity, ambient concentrations of major ions, trace elements and nutrients, and the standing crop of herbivores. Lake level declined during the early years of study, but rose markedly in subsequent years as historically large volumes of water flowed into this hydrologically-closed basin. Winter algal assemblages were dominated (in biomass) most years by small, non-motile chlorophytes ( Choricystis minor, Kirchneriella lunaris or Dunaliella sp.), or Euglena sp. in the most saline sub-basin. Spring assemblages were dominated by diatoms (Stephanodiscus cf. minutulus, Surirella peisonis, Cyclotella meneghiniana and Entomoneis paludosa were especially prominent) or chlorophytes ( C. minor) until the lake level rose. C. minor abundances then declined in spring assemblages and diatoms ( Stephanodiscus cf. agassizensis and S. niagarae; E. paludosa in the more saline sub-basins) dominated. The potential for nitrogen-deficient conditions for phytoplankton growth was evidenced most summers and early autumns by consistently high concentrations of reactive-P relative to inorganic-N and blooms of the N-fixing cyanophyte Aphanizomenon flos-aquae; Microcystis aeruginosa typically was a co-dominant (>30% of biomass) in these assemblages. Pulses of diatoms ( S. cf. agassizensis and C. meneghiniana) occurred in summers following unusually prolonged periods of calm weather or large water inflows. Physical (irradiance, turbulence) and chemical (major nutrients) variables were the primary factors associated with phytoplankton growth. Transparency and major nutrient concentrations accounted for more of the annual variation in phytoplankton structure than did salinity. Seasonal abundance patterns of the dominant zooplankton (the copepod Diaptomus sicilis; the cladocerans Ceriodaphnia quadrangula, Chydorus sphaericus, Daphnia pulex and Diaphanosoma birgei; and the rotifers Brachionus spp., Filinia longiseta, Keratella cochlearis and K. quadrata) also indicated variation in algal populations related to grazing.

Multiplex real time PCR panels to identify fourteen colonization factors of enterotoxigenic Escherichia coli (ETEC).

PubMed

Liu, Jie; Silapong, Sasikorn; Jeanwattanalert, Pimmada; Lertsehtakarn, Paphavee; Bodhidatta, Ladaporn; Swierczewski, Brett; Mason, Carl; McVeigh, Annette L; Savarino, Stephen J; Nshama, Rosemary; Mduma, Esto; Maro, Athanasia; Zhang, Jixian; Gratz, Jean; Houpt, Eric R

2017-01-01

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood diarrhea in low income countries and in travelers to those areas. Inactivated enterotoxins and colonization factors (CFs) are leading vaccine candidates, therefore it is important to determine the prevailing CF types in different geographic locations and populations. Here we developed real time PCR (qPCR) assays for 14 colonization factors, including the common vaccine targets. These assays, along with three enterotoxin targets (STh, STp, and LT) were formulated into three 5-plex qPCR panels, and validated on 120 ETEC isolates and 74 E. coli colony pools. The overall sensitivity and specificity was 99% (199/202) and 99% (2497/2514), respectively, compared to the CF results obtained with conventional PCR. Amplicon sequencing of discrepant samples revealed that the qPCR was 100% accurate. qPCR panels were also performed on nucleic acid extracted from stool and compared to the results of the ETEC isolates or E. coli colony pools cultured from them. 95% (105/110) of the CF detections in the cultures were confirmed in the stool. Additionally, direct testing of stool yielded 30 more CF detections. Among 74 randomly selected E. coli colony pools with paired stool, at least one CF was detected in 63% (32/51) of the colony pools while at least one CF was detected in 78% (47/60) of the stool samples (P = NS). We conclude that these ETEC CF assays can be used on both cultures and stool samples to facilitate better understanding of CF distribution for ETEC epidemiology and vaccine development.

Continuous application of compressive force induces fusion of osteoclast-like RAW264.7 cells via upregulation of RANK and downregulation of LGR4.

PubMed

Matsuike, Rieko; Tanaka, Hideki; Nakai, Kumiko; Kanda, Mai; Nagasaki, Maki; Murakami, Fumiko; Shibata, Chika; Mayahara, Kotoe; Nakajima, Akira; Tanabe, Natsuko; Kawato, Takayuki; Maeno, Masao; Shimizu, Noriyoshi

2018-05-15

During orthodontic treatment, facilitating osteoclastic bone resorption in the alveolar bone exposed to the compressive force (CF) is an important factor for tooth movement. The present study investigated the effect of CF stimulation on the differentiation of RAW264.7 cells from precursors to mature osteoclasts. The cells were continuously stimulated with 0.3, 0.6, or 1.1 g/cm 2 CF-which was generated by increasing the volume of culture medium in the wells of a 96-well plate-in the presence or absence of receptor activator of nuclear factor κB (RANK) ligand (RANKL) for 4 days. In the presence of RANKL, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and the mRNA levels of dendritic cell-specific transmembrane protein (DC-STAMP) and osteoclast-stimulatory transmembrane protein (OC-STAMP) were increased by application of 0.6 and 1.1 g/cm 2 CF as compared to 0.3 g/cm 2 CF. The mRNA level of RANK was upregulated whereas that of leucine-rich repeat-containing G-protein-coupled receptor (LGR)4-another RANKL receptor was downregulated by 0.6 and 1.1 g/cm 2 CF as compared to 0.3 g/cm 2 CF in the absence of RANKL. The proportion of cells with nuclear translocation of the nuclear translocation of nuclear factor of activated T cells (NFAT)c1 was increased by 0.6 and 1.1 g/cm 2 CF in the presence of RANKL. Continuous application of CF induced the differentiation of RAW264.7 cells into TRAP-positive multinuclear cells by enhancing the expression of DC- and OC-STAMP and the nuclear translocation of NFATc1. This may result from the CF-induced increase in RANK and decrease in LGR4 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.

PubMed

Eickmeier, Olaf; Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

2017-01-01

Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients and may serve as a representative peripheral biomarker of the lung resolution program for CF patients.

Relationship Between Fat-Soluble Vitamin Supplementation and Blood Concentrations in Adolescent and Adult Patients With Cystic Fibrosis.

PubMed

Siwamogsatham, Oranan; Dong, Wei; Binongo, Jose N; Chowdhury, Ritam; Alvarez, Jessica A; Feinman, Shawna J; Enders, Jessica; Tangpricha, Vin

2014-08-01

Background: Pancreatic insufficiency is common in patients with cystic fibrosis (CF) and leads to malabsorption of fat-soluble vitamins. Multivitamins, including vitamins A, D, E, and K, are routinely prescribed to patients with CF to prevent vitamin deficiencies. Our objective was to examine the relationship between fat-soluble vitamin supplements and their impact on blood concentrations. Methods: This was a retrospective chart review of patients with CF who were treated at Emory Clinic and Emory University Hospital during 2008-2012. The amount of fat-soluble vitamin supplementation, serum markers of fat-soluble vitamin concentrations, CF transmembrane conductance regulator genotype, and other demographic information were recorded from electronic medical records. Mixed-effects models were used to investigate the trends over time of fat-soluble vitamin supplements and serum vitamin concentrations. Results: In total, 177 charts were eligible. Mean (SD) age was 26.1 (10.2) years. Ninety-two percent of patients had pancreatic insufficiency and 52% had the homozygous ΔF508 mutation. Recorded fat-soluble vitamin supplementation increased in the past 5 years (P < .001 for all). Serum 25-hydroxyvitamin D increased slightly (3% increase; P < .01); however, there were no changes in the blood concentrations of vitamins A, E, and K (P = .26-.96). Conclusions: Despite a near doubling of recorded fat-soluble vitamin supplementation over the past 5 years, there was no parallel increase in blood concentrations of these vitamins. Potential reasons include suboptimal dosages, low adherence, or ongoing issues with malabsorption. © 2014 American Society for Parenteral and Enteral Nutrition.

CFTR gene variant IVS8-5T in disseminated bronchiectasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pignatti, P.F.; Bombieri, C.; Benetazzo, M.

1996-04-01

Obstructive pulmonary disease includes asthma, chronic obstructive pulmonary disease (COPD; i.e., pulmonary emphysema and chronic bronchitis), bronchiectasis, and cystic fibrosis (CF). It represents a leading cause of death in developed countries. Both familial clustering of non-CF obstructive pulmonary disease and familial aggregation of impaired lung function have been described. This suggests that genetic factors contribute to non-CF obstructive pulmonary disease, even if it is difficult to determine the relative contribution of environmental factors. 11 refs., 1 tab.

Numerical study of He/CF{sub 3}I pulsed discharge used to produce iodine atom in chemical oxygen-iodine laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Jiao; Wang Yanhui; Wang Dezhen

2013-04-15

The pulsed discharge for producing iodine atoms from the alkyl and perfluoroalky iodides (CH{sub 3}I, CF{sub 3}I, etc.) is the most efficient method for achieving the pulse operating mode of a chemical oxygen-iodine laser. In this paper, a one-dimensional fluid model is developed to study the characteristics of pulsed discharge in CF{sub 3}I-He mixture. By solving continuity equation, momentum equation, Poisson equation, Boltzmann equation, and an electric circuit equation, the temporal evolution of discharge current density and various discharge products, especially the atomic iodine, are investigated. The dependence of iodine atom density on discharge parameters is also studied. The resultsmore » show that iodine atom density increases with the pulsed width and pulsed voltage amplitude. The mixture ratio of CF{sub 3}I and helium plays a more significant role in iodine atom production. For a constant voltage amplitude, there exists an optimal mixture ratio under which the maximum iodine atom concentration is achieved. The bigger the applied voltage amplitude is, the higher partial pressure of CF{sub 3}I is needed to obtain the maximum iodine atom concentration.« less

Experimental ion mobility measurements in Xe-CF4 mixtures

NASA Astrophysics Data System (ADS)

Cortez, A. F. V.; Kaja, M. A.; Escada, J.; Santos, M. A. G.; Veenhof, R.; Neves, P. N. B.; Santos, F. P.; Borges, F. I. G. M.; Conde, C. A. N.

2018-04-01

In this paper we present the results of the ion mobility measurements made in gaseous mixtures of xenon with carbon tetrafluoride (Xe-CF4) for pressures ranging from 6 to 10 Torr (8-10.6 mbar) and for low reduced electric fields in the 10 to 25 Td range (2.4-6.1 kVṡcm‑1ṡbar‑1), at room temperature. The time-of-arrival spectra revealed one or two peaks depending on the gas relative abundances, which were attributed to CF3+ and to Xe2+ ions. However, for Xe concentrations above 60%, only one peak remains (Xe2+). The reduced mobilities obtained from the peak centroid of the time-of-arrival spectra are presented for Xe concentrations in the 5%-95% range.

Increased (/sup 125/I)trypsin-binding in serum from cystic fibrosis patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, K.L.; Frates, R.C. Jr.; Sheikholislam, B.M.

1982-01-01

The capacities of normal and cystic fibrosis (CF) sera to bind to exogenous human (/sup 125/I)trypsin were compared. Sera from eight older CF patients bound significantly more exogenous human (/sup 125/I)trypsin than did sera from eight normal subjects (p less than 0.001). Disregarding the increased trypsin-binding (TB) of CF sera, serum immunoreactive trypsinogen (SIRT) levels were not detectable in these eight older CF patients. However, when SIRT levels were corrected for TB, four CF patients had normal SIRT concentrations and four had low but detectable SIRT levels. As compared to five normal newborns' sera, serum from a newborn with CFmore » had normal TB and the SIRT levels were very high. In conclusion, increased TB in CF serum lowers results of SIRT assays. Therefore, unless SIRT levels are corrected for TB, results obtained from currently available SIRT kits may be invalid.« less

Monitoring Heavy Metal Contents with Sphagnum Junghuhnianum Moss Bags in Relation to Traffic Volume in Wuxi, China.

PubMed

Hu, Rong; Yan, Yun; Zhou, Xiaoli; Wang, Yanan; Fang, Yanming

2018-02-22

Despite its small size, a moss bag can reveal the different temporal and spatial deposition patterns of pollutants at a particular site; therefore, researchers can use moss bags to determine pollution sources and to put forward strategies for pollution control. Although the use of moss bags to monitor atmospheric pollution has been widely reported in Europe, there are few such empirical studies in China. Thus, in this study, bags containing the moss Sphagnum junghuhnianum were used to assess the concentrations of heavy metals (chromium (Cr), copper (Cu), lead (Pb), vanadium (V), and zinc (Zn)) at five sampling sites (four roads and a forest park) during the summer and winter of 2012. According to the relative accumulation factor (RAF) and contamination factor (CF) results, pollution in winter was heavier than that in summer, and Cr was found to be the most contaminating, having the highest mean CF. There was a significant positive correlation ( p < 0.05) between traffic volume and concentration for three heavy metals (Cr, Cu, and V) in winter, whereas a significant positive correlation ( p < 0.05) was observed between traffic volume and concentrations for four heavy metal elements (Cr, Pb, V, and Zn) in summer, indicating a close relationship between heavy metal contents and traffic volume. Although there was substantial variation in the concentrations of the five heavy metals in the moss bags, significant correlations between heavy metals suggested that the contaminants originated from a common source, namely vehicle emissions. The results demonstrated that the four roads were subject to different degrees of pollution depending on the volume of traffic using each road. Therefore, the results of this study suggest that traffic volume is a major reason for heavy metal pollution.

Monitoring Heavy Metal Contents with Sphagnum Junghuhnianum Moss Bags in Relation to Traffic Volume in Wuxi, China

PubMed Central

Hu, Rong; Yan, Yun; Zhou, Xiaoli; Wang, Yanan; Fang, Yanming

2018-01-01

Despite its small size, a moss bag can reveal the different temporal and spatial deposition patterns of pollutants at a particular site; therefore, researchers can use moss bags to determine pollution sources and to put forward strategies for pollution control. Although the use of moss bags to monitor atmospheric pollution has been widely reported in Europe, there are few such empirical studies in China. Thus, in this study, bags containing the moss Sphagnum junghuhnianum were used to assess the concentrations of heavy metals (chromium (Cr), copper (Cu), lead (Pb), vanadium (V), and zinc (Zn)) at five sampling sites (four roads and a forest park) during the summer and winter of 2012. According to the relative accumulation factor (RAF) and contamination factor (CF) results, pollution in winter was heavier than that in summer, and Cr was found to be the most contaminating, having the highest mean CF. There was a significant positive correlation (p < 0.05) between traffic volume and concentration for three heavy metals (Cr, Cu, and V) in winter, whereas a significant positive correlation (p < 0.05) was observed between traffic volume and concentrations for four heavy metal elements (Cr, Pb, V, and Zn) in summer, indicating a close relationship between heavy metal contents and traffic volume. Although there was substantial variation in the concentrations of the five heavy metals in the moss bags, significant correlations between heavy metals suggested that the contaminants originated from a common source, namely vehicle emissions. The results demonstrated that the four roads were subject to different degrees of pollution depending on the volume of traffic using each road. Therefore, the results of this study suggest that traffic volume is a major reason for heavy metal pollution. PMID:29470433

A Calibration-Free Laser-Induced Breakdown Spectroscopy (CF-LIBS) Quantitative Analysis Method Based on the Auto-Selection of an Internal Reference Line and Optimized Estimation of Plasma Temperature.

PubMed

Yang, Jianhong; Li, Xiaomeng; Xu, Jinwu; Ma, Xianghong

2018-01-01

The quantitative analysis accuracy of calibration-free laser-induced breakdown spectroscopy (CF-LIBS) is severely affected by the self-absorption effect and estimation of plasma temperature. Herein, a CF-LIBS quantitative analysis method based on the auto-selection of internal reference line and the optimized estimation of plasma temperature is proposed. The internal reference line of each species is automatically selected from analytical lines by a programmable procedure through easily accessible parameters. Furthermore, the self-absorption effect of the internal reference line is considered during the correction procedure. To improve the analysis accuracy of CF-LIBS, the particle swarm optimization (PSO) algorithm is introduced to estimate the plasma temperature based on the calculation results from the Boltzmann plot. Thereafter, the species concentrations of a sample can be calculated according to the classical CF-LIBS method. A total of 15 certified alloy steel standard samples of known compositions and elemental weight percentages were used in the experiment. Using the proposed method, the average relative errors of Cr, Ni, and Fe calculated concentrations were 4.40%, 6.81%, and 2.29%, respectively. The quantitative results demonstrated an improvement compared with the classical CF-LIBS method and the promising potential of in situ and real-time application.

Dynamic controlled atmosphere and ultralow oxygen storage on 'Gala' mutants quality maintenance.

PubMed

Thewes, Fabio Rodrigo; Both, Vanderlei; Brackmann, Auri; Weber, Anderson; de Oliveira Anese, Rogerio

2015-12-01

The aim of the present work was to compare the effect of ultralow oxygen (ULO) with dynamic controlled atmosphere (DCA) and controlled atmosphere (CA) on the post storage quality of 'Royal Gala' and 'Galaxy' apples after long-term storage. Two experiments were carried out with 'Royal Gala' and 'Galaxy' apples, in the years 2012 and 2013, respectively. A higher internal ethylene concentration was observed in fruits stored under CA; intermediate concentration in fruits under ULO; and the lowest by fruits stored under DCA-CF (DCA based on chlorophyll fluorescence). Flesh firmness was higher in fruits stored under DCA-CF and ULO differing from CA, in the year 2012, but in 2013 fruits stored under ULO showed the highest flesh firmness, differing from CA fruits. DCA-CF is efficient in quality maintenance of 'Royal Gala' and 'Galaxy' apples. Both 'Gala' mutants stored under ULO show a similar quality maintenance to those stored under DCA-CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-efficiency l-lactic acid production by Rhizopus oryzae using a novel modified one-step fermentation strategy.

PubMed

Fu, Yong-Qian; Yin, Long-Fei; Zhu, Hua-Yue; Jiang, Ru

2016-10-01

In this study, lactic acid fermentation by Rhizopus oryzae was investigated using the two different fermentation strategies of one-step fermentation (OSF) and conventional fermentation (CF). Compared to CF, OSF reduced the demurrage of the production process and increased the production of lactic acid. However, the qp was significantly lower than during CF. Based on analysis of μ, qs and qp, a novel modified OSF strategy was proposed. This strategy aimed to achieve a high final concentration of lactic acid, and a high qp by R. oryzae. In this strategy, the maximum lactic acid concentration and productivity of the lactic acid production stage reached 158g/l and 5.45g/(lh), which were 177% and 366% higher, respectively, than the best results from CF. Importantly, the qp and yield did not decrease. This strategy is a convenient and economical method for l-lactic acid fermentation by R. oryzae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Carotid-femoral pulse wave velocity in a healthy adult sample: The ELSA-Brasil study.

PubMed

Baldo, Marcelo Perim; Cunha, Roberto S; Molina, Maria Del Carmen B; Chór, Dora; Griep, Rosane H; Duncan, Bruce B; Schmidt, Maria Inês; Ribeiro, Antonio L P; Barreto, Sandhi M; Lotufo, Paulo A; Bensenor, Isabela M; Pereira, Alexandre C; Mill, José Geraldo

2018-01-15

Aging declines essential physiological functions, and the vascular system is strongly affected by artery stiffening. We intended to define the age- and sex-specific reference values for carotid-to-femoral pulse wave velocity (cf-PWV) in a sample free of major risk factors. The ELSA-Brasil study enrolled 15,105 participants aged 35-74years. The healthy sample was achieved by excluding diabetics, those over the optimal and normal blood pressure levels, body mass index ≤18.5 or ≥25kg/m 2 , current and former smokers, and those with self-report of previous cardiovascular disease. After exclusions, the sample consisted of 2158 healthy adults (1412 women). Although cf-PWV predictors were similar between sex (age, mean arterial pressure (MAP) and heart rate), cf-PWV was higher in men (8.74±1.15 vs. 8.31±1.13m/s; adjusted for age and MAP, P<0.001) for all age intervals. When divided by MAP categories, cf-PWV was significantly higher in those which MAP ≥85mmHg, regardless of sex, and for all age intervals. Risk factors for arterial stiffening in the entire ELSA-Brasil population (n=15,105) increased by twice the age-related slope of cf-PWV growth, regardless of sex (0.0919±0.182 vs. 0.0504±0.153m/s per year for men, 0.0960±0.173 vs. 0.0606±0.139m/s per year for women). cf-PWV is different between men and women and even in an optimal and normal range of MAP and free of other classical risk factors for arterial stiffness, reference values for cf-PWV should take into account MAP levels. Also, the presence of major risk factors in the general population doubles the age-related rise in cf-PWV. Copyright © 2017 Elsevier B.V. All rights reserved.

UK NHS pilot study on cell-free DNA testing in screening for fetal trisomies: factors affecting uptake.

PubMed

Gil, M M; Giunta, G; Macalli, E A; Poon, L C; Nicolaides, K H

2015-01-01

This study reports on the clinical implementation of cell-free DNA (cfDNA) testing, contingent on the results of the combined test, in screening for fetal trisomies 21, 18 and 13 in two UK National Health Service hospitals. Women with a combined-test risk of ≥ 1:100 (high risk) were offered the options of chorionic villus sampling (CVS), cfDNA testing or no further testing and those with a risk of 1:101 to 1:2500 (intermediate risk) were offered cfDNA or no further testing. The objective of the study was to examine the factors affecting patient decisions concerning their options. Combined screening was performed in 6651 singleton pregnancies in which the risk for trisomies was high in 260 (3.9%), intermediate in 2017 (30.3%) and low in 4374 (65.8%). Logistic regression analysis was used to determine which factors among maternal characteristics, fetal nuchal translucency thickness (NT) and risk for trisomies were significant predictors of opting for CVS in the high-risk group and opting for cfDNA testing in the intermediate-risk group. In the high-risk group, 104 (40.0%) women opted for CVS; predictors for CVS were increasing fetal NT and increasing risk for trisomies, while the predictor against CVS was being of Afro-Caribbean racial origin (r = 0.366). In the intermediate-risk group, 1850 (91.7%) women opted for cfDNA testing; predictors for cfDNA testing were increasing maternal age, increasing risk for trisomies and university education, while predictors against cfDNA testing were being of Afro-Caribbean racial origin, smoking and being parous (r = 0.105). This study has identified factors that can influence the decision of women undergoing combined screening in favor of or against CVS and in favor of or against cfDNA testing. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Independent associations of physical activity and cardiovascular fitness with cardiovascular risk in adults.

PubMed

Ekblom-Bak, Elin; Hellénius, Mai-Lis; Ekblom, Orjan; Engström, Lars-Magnus; Ekblom, Björn

2010-04-01

Uncertainty still exists whether physical activity (PA) and cardiovascular fitness (CF) contribute separately to cardiovascular disease (CVD) risk. This study examined the associations of PA and CF on individual as well as clustered CVD risk factors. Cross-sectional. Seven hundred and eighty-one men and 890 women, aged 20-65 years, from two random population-based samples of Swedish women and men were included. PA was assessed by questionnaire and CF was predicted by a submaximal cycle ergometry test. Waist circumference, blood pressure, and fasting levels of blood lipids were assessed and dichotomized by conventional cut-off points. Participants reporting high PA level benefited from lower triglycerides and atherogenic cholesterol levels, regardless of CF. Higher CF level was, regardless of PA, associated with lower risk for all risk factors. With regard to clustering of risk factors, each higher CF level was associated with a gradually reduced risk by half or more, independent of PA. Furthermore, being unfit but reporting high PA was associated with a 50% lower risk compared with being unfit and inactive. Furthermore, high reported PA was associated with an additional reduced risk among fit participants. In addition, an excess risk of interaction was found for waist circumference, triglycerides, and the clustered CVD risk between neither being sufficiently active nor being fit. This study suggests that both PA and CF are independently associated with lower cardiovascular risk, and that both variables should be taken into account when CVD risk is estimated.

Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study.

PubMed

Choo, Jina; Shin, Chol; Barinas-Mitchell, Emma; Masaki, Kamal; Willcox, Bradley J; Seto, Todd B; Ueshima, Hirotsugu; Lee, Sunghee; Miura, Katsuyuki; Venkitachalam, Lakshmi; Mackey, Rachel H; Evans, Rhobert W; Kuller, Lewis H; Sutton-Tyrrell, Kim; Sekikawa, Akira

2014-01-13

Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors. A population-based sample of healthy 784 men aged 40-49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking. Among healthy men aged 40 - 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.

The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

PubMed

Glinz, Dominik; Hurrell, Richard F; Ouattara, Mamadou; Zimmermann, Michael B; Brittenham, Gary M; Adiossan, Lukas G; Righetti, Aurélie A; Seifert, Burkhardt; Diakité, Victorine G; Utzinger, Jürg; N'Goran, Eliézer K; Wegmüller, Rita

2015-09-17

Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 μg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Blocking effect of rheumatoid factor and cold agglutinins on complement fixation tests for histoplasmosis.

PubMed Central

Johnson, J E; Roberts, G D

1976-01-01

The blocking effect of rheumatoid factor (RF) and cold agglutinins (CA) on the detection of complement-fixing (CF) antibodies for Histoplasma capsulatum using a mycelial (histoplasmin) and a yeast antigen was studied. Sera from 213 patients serologically positive for histoplasmosis were screened for the presence of RF or CA. CF antibodies to H. capsulatum in sera containing RF or CA were studied before and after removal of these factors (RF and CA) by treatment with dithiothreitol. Results suggest that RF or CA may interfere with the CF reaction to the yeast antigen of H. capsulatum but not to the mycelial antigen (histoplasmin). PMID:1254713

Golgi-Colonnier method: correlation of the degree of chromium reduction and pH change with quality of staining.

PubMed

Angulo, A; Merchán, J A; Molina, M

1994-03-01

We examined the role of chromium reduction in the Golgi-Colonnier method, correlating the quality of neuronal impregnation with the levels of hexavalent (CrVI) and trivalent (CrIII) chromium in the tissue and in the chromation fluid (CF). The concentrations of both chromium species were assessed by measuring spectrophotometrically the CrVI before and after oxidizing the sample and by calculating the ratio of CrVI to total chromium (chromium ratio, CrR). The CrR was almost identical in the tissue and the CF, decreasing exponentially during chromation due to a progressive consumption of CrVI to form CrIII. Satisfactory cell impregnation was obtained only when the CrR was 0.45-0.7, regardless of other factors. The CrR values could be accurately predicted by the pH increase of the CF; this increase has proven to be a most reliable criterion to decide the endpoint of the chromation process. The dependence of cell staining on the [CrIII], together with the well-known ability of this species to bridge proteins, suggests that the key event for cell impregnation is the cross-linking of neuronal proteins by CrIII polymers.

The Certification Framework: Risk Assessment for Safety and Effectiveness of Geologic Carbon Sequestration

NASA Astrophysics Data System (ADS)

Oldenburg, C. M.; Nicot, J.; Bryant, S. L.

2008-12-01

Motivated by the dual objectives of (1) encouraging geologic carbon sequestration (GCS) as one of several strategies urgently needed to reduce CO2 emissions, and (2) protecting the environment from unintended CO2 injection-related impacts, we have developed a simple and transparent framework for certifying GCS safety and effectiveness at individual sites. The approach we developed, called the Certification Framework (CF), is proposed as a standard way for project proponents, regulators, and the public to analyze and understand risks and uncertainties of GCS. In the CF, we relate effective trapping to CO2 leakage risk, where we use the standard definition of risk involving the two factors (1) probability of a particular leakage scenario, and (2) impact of that leakage scenario. In short, if the CO2 leakage risk as calculated by the CF is below threshold values for the life of the project, then effective trapping is predicted and the site can be certified. The concept of effective trapping is more general than traditional "no migration" approaches to underground injection regulation. We achieve simplicity in the CF by using (1) wells and faults as the potential leakage pathways, (2) five compartments to represent where impacts can occur (underground sources of drinking water, hydrocarbon and mineral resources, near-surface environment, health and safety, and emission credits and atmosphere), (3) modeled CO2 fluxes and concentrations as proxies for impact to compartments, (4) broad ranges of storage formation properties to generate a catalog of simulated CO2 plumes, and (5) probabilities of intersection of the CO2 plume with the conduits and compartments. In a case study application of the CF for a saline formation GCS site in the Texas Gulf Coast, analysis with the CF suggested the overall leakage risk to be very small, with the largest contribution coming from risk to the near-surface environment due to potential leakage up abandoned wells, depending on the effective permeability assumed for the wells. This result shows that risk could be drastically reduced by locating and monitoring abandoned wells, along with well or leakage mitigation if necessary. By this means, effective trapping can be predicted with greater certainty because both factors of risk (probability of well leakage, and impact of well leakage) can be reduced significantly through surface monitoring and mitigation, if needed.

Chinese Secondary EFL Learners' and Teachers' Preferences for Types of Written Corrective Feedback

ERIC Educational Resources Information Center

Li, Haishan; He, Qingshun

2017-01-01

How learners perceive written corrective feedback (CF) associates with its effectiveness in language learning. This research investigates students' preferences for three types of written CF, i.e., direct, indirect and metalinguistic written CF, and explores the factors that encourage the teachers to employ these CFs in teaching practice. The…

High Energy Halogen Chemistry.

DTIC Science & Technology

1978-01-01

underwent addition of triflic acid and of hydrochloric acid . The oxetane was polymerized ~zith phosphorous pentaflucride to ~lve a polymer stable to 2900...in aqueous dioxane . The oxetane was not affected by boron trifluoride etherate In chloroform, or by methanolic solutions of sulfuric or triflic acids ...concentrated hydrochloric acid to give 3-chloro-2-fluoro-2-nitro-l-propanol. NO • i 2 NO2OH CF I + CF SOH— 3 CF SO OCH CCH OH O OH ~ 3 3 2 2~ 2 F NO NO

Analysis of the Effect of Cyclophosphamide and Methotrexate on Chrysomya megacephala (Diptera: Calliphoridae).

PubMed

Trivia, Ana Letícia; de Carvalho Pinto, Carlos José

2018-01-19

Forensic entomotoxicology investigates the effects of chemical substances in the development of scavenger insects and the reflection on estimating the minimum postmortem interval (PMI). To evaluate the impact of the chemotherapeutic drugs cyclophosphamide (CF) and methotrexate (MTX) on the postembryonic development of Chrysomya megacephala, controlled experiments were performed by rearing the larvae on spiked minced beef with different concentrations of these drugs. The results indicated that CF significantly decreased their developmental rate up to 28 h but had no significant effect on larval and adult sizes, survival rate, and sex ratio, whereas MTX decreased larval and adult sizes, survival rate, and there was a deviation in the expected sex ratio toward females in MTX-exposed larvae but had no significant impact on developmental rate. These negative interference factors should be considered in cases of suspected death of people that have undergone chemotherapy. © 2018 American Academy of Forensic Sciences.

Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

PubMed Central

Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

2015-01-01

Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

PubMed

De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

Improvement of mechanical strength of sintered Mo alloyed steel by optimization of sintering and cold-forging processes with densification

NASA Astrophysics Data System (ADS)

Kamakoshi, Y.; Shohji, I.; Inoue, Y.; Fukuda, S.

2017-10-01

Powder metallurgy (P/M) materials have been expected to be spread in automotive industry. Generally, since sintered materials using P/M ones contain many pores and voids, mechanical properties of them are inferior to those of conventional wrought materials. To improve mechanical properties of the sintered materials, densification is effective. The aim of this study is to improve mechanical strength of sintered Mo-alloyed steel by optimizing conditions in sintering and cold-forging processes. Mo-alloyed steel powder was compacted. Then, pre-sintering (PS) using a vacuum sintering furnace was conducted. Subsequently, coldforging (CF) by a backward extrusion method was conducted to the pre-sintered specimen. Moreover, the cold-forged specimen was heat treated by carburizing, tempering and quenching (CQT). Afterwards, mechanical properties were investigated. As a result, it was found that the density of the PS specimen is required to be more than 7.4 Mg/m3 to strengthen the specimen by heat treatment after CF. Furthermore, density and the microstructure of the PS specimen are most important factors to make the high density and strength material by CF. At the CF load of 1200 kN, the maximum density ratio reached approximately 99% by the use of the PS specimen with proper density and microstructure. At the CF load of 900 kN, although density ratio was high like more than 97.8%, transverse rupture strength decreased sharply. Since densification caused high shear stress and stress concentration in the surface layer, microcracks occurred by the damages of inter-particle sintered connection of the surface layer. On the contrary, in case of the CF load of 1200 kN, ultra-densification of the surface layer occurred by a sufficient plastic flow. Such sufficient compressed specimens regenerated the sintered connections by high temperature heat treatment and thus the high strength densified material was obtained. These processes can be applicable to near net shape manufacturing without surface machining.

Influence of water chemistry on the acute toxicity of copper and zinc to the cladoceran Ceriodaphnia cf dubia.

PubMed

Hyne, Ross V; Pablo, Fleur; Julli, Moreno; Markich, Scott J

2005-07-01

This study determined the influence of key water chemistry parameters (pH, alkalinity, dissolved organic carbon [DOC], and hardness) on the aqueous speciation of copper and zinc and its relationship to the acute toxicity of these metals to the cladoceran Ceriodaphnia cf dubia. Immobilization tests were performed for 48-h in synthetic or natural waters buffered at various pH values from 5.5 to 8.4 (other chemical parameters held constant). The toxicity of copper to C. cf dubia decreased fivefold with increasing pH, whereas the toxicity of zinc increased fivefold with increasing pH. The effect of DOC on copper and zinc toxicity to C. cf dubia was determined using natural fulvic acid in the synthetic water. Increasing DOC was found to decrease linearly the toxicity of copper, with the mean effect concentration of copper that immobilized 50% of the cladocerans (EC50) value 45 times higher at 10 mg/L, relative to 0.1 mg/L DOC at pH 6.5. In contrast, the addition of 10 mg/L DOC only resulted in a very small (1.3-fold) reduction in the toxicity of zinc to C. cf dubia. Copper toxicity to C. cf dubia generally did not vary as a function of hardness, whereas zinc toxicity was reduced by a factor of only two, with an increase in water hardness from 44 to 374 mg CaCO3/L. Increasing bicarbonate alkalinity of synthetic waters (30-125 mg/L as CaCO3) decreased the toxicity of copper up to fivefold, which mainly could be attributed to the formation of copper-carbonate complexes, in addition to a pH effect. The toxicity of copper added to a range of natural waters with varying DOC content, pH, and hardness was consistent with the toxicity predicted using the data obtained from the synthetic waters.

Mercury concentrations in gonad, liver, and muscle of white sturgeon Acipenser transmontanus in the lower Columbia River.

PubMed

Webb, M A H; Feist, G W; Fitzpatrick, M S; Foster, E P; Schreck, C B; Plumlee, M; Wong, C; Gundersen, D T

2006-04-01

This study determined the partitioning of total mercury in liver, gonad, and cheek muscle of white sturgeon (Acipenser transmonatus) in the lower Columbia River. The relationship between tissue mercury concentrations and various physiologic parameters was assessed. White sturgeon were captured in commercial fisheries in the estuary and Bonneville, The Dalles, and John Day Reservoirs. Condition factor (CF), relative weight (Wr), and gonadosomatic index (GSI) were determined for each fish (n = 57). Gonadal tissue was examined histologically to determine sex and stage of maturity. Liver (n = 49), gonad (n = 49), and cheek muscle (n = 57) were analyzed for total mercury using cold-vapor atomic fluorescence spectrophotometry. Tissue protein concentrations were measured by ultraviolet-visible spectroscopy. Plasma was analyzed for testosterone (T), 11-ketotestosterone (KT), and 17ss-estradiol (E2) using radioimmunoassay. Mean tissue mercury concentrations were higher in muscle compared with liver and gonad at all sampling locations, except Bonneville Reservoir where mean liver mercury content was the highest tissue concentration observed in the study. Significant negative correlations between plasma androgens (T and KT) and muscle mercury content and plasma E2 and liver mercury content were found. A significant positive linear relationship between white sturgeon age and liver mercury concentrations was evident. Significant negative correlations between CF and relative weight and gonad and liver mercury content were found. In addition, immature male sturgeon with increased gonad mercury content had decreased GSIs. These results suggest that mercury, in the form of methylmercury, may have an effect on the reproductive potential of white sturgeon.

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

PubMed

Helmi, Mohamed; Love, Robert B; Welter, Debbie; Cornwell, Richard D; Meyer, Keith C

2003-03-01

To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. A university hospital. Lung transplant recipients with CF or other indications for transplantation. None. Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.

Analysis of electronic parameters and frequency-dependent properties of Au/NiO/ n-GaN heterojunctions

NASA Astrophysics Data System (ADS)

Reddy, Varra Niteesh; Padma, R.; Gunasekhar, K. R.

2018-01-01

The electrical and frequency-dependent properties of ten Au/NiO/ n-GaN heterojunctions fabricated with similar conditions are assessed by I-V, C-V, and G-V measurement methods. In addition, C-f and G-f measurements are conducted in the frequency range of 1 kHz-1 MHz. The electronic parameters are changed from junction to junction even if they are fabricated in the similar way. The calculated barrier height and ideality factor values are fitted by the Gaussian distribution function. Statistical analysis of the data provides the mean barrier height and ideality factor values of 0.84 eV and 2.70 for the heterojunction. Besides, the mean barrier height ( V b), donor concentration ( N d), space charge layer width ( W D), and Fermi level ( E F) are determined from the C-V data and the corresponding values are 1.30 eV, 2.00 × 1017 cm-3, 8.222 × 10-6 cm, and 0.018 eV, respectively. The interface state density ( N SS) and relaxation time (τ) are assessed from C-f and G-f measurements. Moreover, the dielectric constant ( ɛ'), dielectric loss ( ɛ″), tangent loss (tan δ), and electrical conductivity ( σ ac) are determined from C-f and G-f data in the frequency range of 1 kHz-1 MHz with various biases (0.1-0.6 V). ɛ' and ɛ″ are decreased with increasing frequency.

Removal of ammonium and heavy metals by cost-effective zeolite synthesized from waste quartz sand and calcium fluoride sludge.

PubMed

Zhang, Qian; Lin, Bing; Hong, Junming; Chang, Chang-Tang

2017-02-01

This study focuses on the effectiveness of zeolite (10% CF-Z [0.5]) hydrothermally synthesized from waste quartz sand and calcium fluoride (CF) for ammonium ion and heavy metal removal. Zeolite was characterized through powder X-ray diffraction, Fourier-transform infrared spectroscopy, micromeritics N 2 adsorption/desorption analysis, and field emission scanning electron microscopy. The effects of CF addition, Si/Al ratio, initial ammonium concentration, solution pH, and temperature on the adsorption of ammonium on 10% CF-Z (0.5) were further examined. Results showed that 10% CF-Z (0.5) was a single-phase zeolite A with cubic-shaped crystals and 10% CF-Z (0.5) efficiently adsorbs ammonium and heavy metals. For instance, 91% ammonium (10 mg L -1 ) and 93% lead (10 mg L -1 ) are removed. The adsorption isotherm, kinetics, and thermodynamics of ammonium adsorption on 10% CF-Z (0.5) were also theoretically analyzed. The adsorption isotherm of ammonium and lead on 10% CF-Z (0.5) in single systems indicated that Freundlich model provides the best fit for the equilibrium data, whereas pseudo-second-order model best describes the adsorption kinetics. The adsorption degree of ions on 10% CF-Z (0.5) in mixed systems exhibits the following pattern: lead > ammonium > cadmium > chromium.

Supplementation with Red Palm Oil Increases β-Carotene and Vitamin A Blood Levels in Patients with Cystic Fibrosis

PubMed Central

Sommerburg, Olaf; De Spirt, Silke; Mattern, Annett; Joachim, Cornelia; Langhans, Claus-Dieter; Nesaretnam, Kalanithi; Siems, Werner; Stahl, Wilhelm; Mall, Marcus A.

2015-01-01

Patients with cystic fibrosis (CF) show decreased plasma concentrations of antioxidants due to malabsorption of lipid soluble vitamins and consumption by chronic pulmonary inflammation. β-Carotene is a major source of retinol and therefore is of particular significance in CF. The aim of this study was to investigate the effect of daily intake of red palm oil (RPO) containing high amounts of β-carotene on the antioxidant levels in CF patients. Sixteen subjects were recruited and instructed to enrich their food with 2 to 3 tablespoons of RPO (~1.5 mg of β-carotene) daily over 8 weeks. Carotenoids, retinol, and α-tocopherol were measured in plasma at baseline and after intervention. In addition β-carotene, lycopene, α-tocopherol, and vitamin C were measured in buccal mucosa cells (BMC) to determine the influence of RPO on antioxidant tissue levels. Eleven subjects completed the study properly. Plasma β-carotene, retinol, and α-carotene of these patients increased, but plasma concentrations of other carotenoids and α-tocopherol as well as concentrations of β-carotene, lycopene, α-tocopherol, and vitamin C in BMC remained unchanged. Since RPO on a daily basis did not show negative side effects the data suggest that RPO may be used to elevate plasma β-carotene in CF. PMID:25688177

Synthesis of Metal-Oxide/Carbon-Fiber Heterostructures and Their Properties for Organic Dye Removal and High-Temperature CO2 Adsorption

NASA Astrophysics Data System (ADS)

Shao, Liangzhi; Nie, Shibin; Shao, Xiankun; Zhang, LinLin; Li, Benxia

2018-03-01

One-dimensional metal-oxide/carbon-fiber (MO/CF) heterostructures were prepared by a facile two-step method using the natural cotton as a carbon source the low-cost commercial metal salts as precursors. The metal oxide nanostructures were first grown on the cotton fibers by a solution chemical deposition, and the metal-oxide/cotton heterostructures were then calcined and carbonized in nitrogen atmosphere. Three typical MO/CF heterostructures of TiO2/CF, ZnO/CF, and Fe2O3/CF were prepared and characterized. The loading amount of the metal oxide nanostructures on carbon fibers can be tuned by controlling the concentration of metal salt in the chemical deposition process. Finally, the performance of the as-obtained MO/CF heterostructures for organic dye removal from water was tested by the photocatalytic degradation under a simulated sunlight, and their properties of high-temperature CO2 adsorption were predicted by the temperature programmed desorption. The present study would provide a desirable strategy for the synthesis of MO/CF heterostructures for various applications.

Natural radionuclides in fish species from surface water of Bagjata and Banduhurang uranium mining areas, East Singhbhum, Jharkhand, India.

PubMed

Giri, Soma; Singh, Gurdeep; Jha, V N; Tripathi, R M

2010-11-01

To study the natural radionuclides in the freshwater fish samples around the uranium mining areas of Bagjata and Banduhurang, East Singhbhum, Jharkhand, India. The naturally occurring radioisotopes of uranium, U(nat), consisting of (234)U, (235)U and (238)U; (226)Ra, (230)Th and (210)Po were analysed in the fish samples from the surface water of Bagjata and Banduhurang mining areas after acid digestion. The ingestion dose, concentration factor and excess lifetime cancer risk of the radionuclides were estimated. The geometric mean activity of U(nat), (226)Ra, (230)Th and (210)Po in the fish samples was found to be 0.05, 0.19, 0.29 and 0.95 Bq kg(-1)(fresh) (Becquerel per kilogram fresh fish), respectively, in the Bagjata mining area, while for Banduhurang mining area it was estimated to be 0.08, 0.41, 0.22 and 2.48 Bq kg(-1)(fresh), respectively. The ingestion dose was computed to be 1.88 and 4.16 μSvY(-1), respectively, for both the areas which is much below the 1 mSv limit set in the new International Commission on Radiological Protection (ICRP) recommendations. The estimation of the Concentration Factors (CF) reveal that the CF from water is greater than 1 l/kg(-1)in most of the cases while from sediment CF is less than 1. The excess individual lifetime cancer risk due to the consumption of fish was calculated to be 2.53 × 10(-5) and 6.48 × 10(-5), respectively, for Bagjata and Banduhurang areas, which is within the acceptable excess individual lifetime cancer risk value of 1 × 10(-4). The study confirms that current levels of radioactivity do not pose a significant radiological risk to freshwater fish consumers.

Long-term effect of early nutrition on endocrine parameters and liver and endometrial gene expression of the members of the somatotrophic axis in Hereford heifers.

PubMed

Guggeri, D; Meikle, A; Carriquiry, M; De Barbieri, I; Montossi, F; Viñoles, C

2018-04-23

This study compared the effect of different management systems on endocrine parameters, and gene expression of members of the somatotrophic axis in the liver and endometrium of beef heifers. Twenty-two 709-days-old heifers submitted to Early Weaning (EW, n = 8), Traditional Weaning (TW, n = 7) and TW plus creep feeding (TW+CF, n = 7) were used. Animals were synchronized with two prostaglandin (PG) injections at 11-day interval (Oestrus = Day 0). Blood samples were collected daily for progesterone (P4) determination, and endometrial and liver biopsies on Days 7 and 16 for transcript determination of members of the somatotrophic axis. Progesterone concentrations were greater on Days 15 and 16 (p < .02) of the cycle in TW+CF than TW and EW heifers. On Day 7, TW+CF heifers expressed greater liver total growth hormone receptor transcripts than TW heifers (p = .05) and greater insulin-like growth factor (IGF)-binding protein 3 mRNA than both EW and TW groups (p < .05). On Days 7 and 16, TW+CF expressed more endometrial IGF1 mRNA than the other groups (p < .01). We conclude that increasing the plane of nutrition of nursing calves may have a long-term effect on the functioning of the somatotrophic axis both in the liver and in the endometrium. © 2018 Blackwell Verlag GmbH.

Crystal Structure of the 25 kDa Subunit of Human Cleavage Factor I{m}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coseno,M.; Martin, G.; Berger, C.

Cleavage factor Im is an essential component of the pre-messenger RNA 3'-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor Im is an oligomer composed of a small 25 kDa subunit (CF Im25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein-protein interactions are thought to be facilitated by the Nudix domain of CF Im25, a hydrolase motif with a characteristic {alpha}/{beta}/{alpha} fold and a conserved catalytic sequence or Nudix box. We present heremore » the crystal structures of human CF Im25 in its free and diadenosine tetraphosphate (Ap4A) bound forms at 1.85 and 1.80 Angstroms, respectively. CF Im25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF Im25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap4A. The complex and apo protein structures provide insight into the active oligomeric state of CF Im and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3'-end processing.« less

Crystal structure of the 25 kDa subunit of human cleavage factor Im

PubMed Central

Coseno, Molly; Martin, Georges; Berger, Christopher; Gilmartin, Gregory; Keller, Walter; Doublié, Sylvie

2008-01-01

Cleavage factor Im is an essential component of the pre-messenger RNA 3′-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor Im is an oligomer composed of a small 25 kDa subunit (CF Im25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein–protein interactions are thought to be facilitated by the Nudix domain of CF Im25, a hydrolase motif with a characteristic α/β/α fold and a conserved catalytic sequence or Nudix box. We present here the crystal structures of human CF Im25 in its free and diadenosine tetraphosphate (Ap4A) bound forms at 1.85 and 1.80 Å, respectively. CF Im25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF Im25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap4A. The complex and apo protein structures provide insight into the active oligomeric state of CF Im and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3′-end processing. PMID:18445629

Validation of a nutrition risk screening tool for children and adolescents with cystic fibrosis ages 2-20 years.

PubMed

McDonald, Catherine M

2008-04-01

According to the 2002 Cystic Fibrosis (CF) Foundation nutrition consensus report, children with CF should grow normally. Cross-sectional data from the foundation's patient registry concluded that a body mass index at or greater than the 50th percentile is associated with better lung function. A consistent, evidence-based screening process can identify those individuals with CF having nutrition risk factors associated with a decrease in pulmonary function, target early intervention, and prevent further decline. A tool for screening nutrition risk is described to identify those children with CF who would benefit from more extensive nutrition intervention. The proposed screening tool is a risk-based classification system with 3 categories: weight gain, height velocity, and body mass index. The CF Foundation recommendations regarding these parameters are incorporated, with risk points assigned when minimum body mass index, weight gain, and/or height gain standards are unmet. An interrater measure of agreement determined a satisfactory level of reliability (kappa = 0.85). Patient records (n = 85) were reviewed to determine nutrition status category (no risk or at risk) of this tool compared with the CF Foundation 2002 Nutrition Consensus, yielding sensitivity and specificity at 84% and 75%, respectively. A second comparison was made with combined, independent nutrition risk factors not included in the screening tool. The sensitivity and specificity of the screening tool compared with the combined risk factors were 86% and 78%, respectively. This tool for screening nutrition risk for CF is reliable and valid, with consistent, reproducible results, free from subject or observer bias.

Application of the threshold of toxicological concern approach for the safety evaluation of calendula flower (Calendula officinalis) petals and extracts used in cosmetic and personal care products.

PubMed

Re, T A; Mooney, D; Antignac, E; Dufour, E; Bark, I; Srinivasan, V; Nohynek, G

2009-06-01

Calendula flower (Calendula officinalis) (CF) has been used in herbal medicine because of its anti-inflammatory activity. CF and C. officinalis extracts (CFE) are used as skin conditioning agents in cosmetics. Although data on dermal irritation and sensitization of CF and CFE's are available, the risk of subchronic systemic toxicity following dermal application has not been evaluated. The threshold of toxicological concern (TTC) is a pragmatic, risk assessment based approach that has gained regulatory acceptance for food and has been recently adapted to address cosmetic ingredient safety. The purpose of this paper is to determine if the safe use of CF and CFE can be established based upon the TTC class for each of its known constituents. For each constituent, the concentration in the plant, the molecular weight, and the estimated skin penetration potential were used to calculate a maximal daily systemic exposure which was then compared to its corresponding TTC class value. Since the composition of plant extracts are variable, back calculation was used to determine the maximum acceptable concentration of a given constituent in an extract of CF. This paper demonstrates the utility and practical application of the TTC concept when used as a tool in the safety evaluation of botanical extracts.

Revisiting sweat chloride test results based on recent guidelines for diagnosis of cystic fibrosis.

PubMed

Pagaduan, Jayson V; Ali, Mahesheema; Dowlin, Michael; Suo, Liye; Ward, Tabitha; Ruiz, Fadel; Devaraj, Sridevi

2018-03-01

Recent sweat chloride guidelines published by the Cystic Fibrosis Foundation changed the intermediate sweat chloride concentration range from 40-59 mmol/L to 30-59 mmol/L for age > 6 months. We wanted to know how this new guideline would impact detection of cystic fibrosis among patients who previously had sweat tests done at Texas Children's Hospital. We revisited sweat chloride test results (n = 3012) in the last 5 years at Texas Children's Hospital based on the new guidelines on diagnosis of cystic fibrosis from the Cystic Fibrosis Foundation. We identified 125 patients that would be reclassified in the intermediate sweat chloride value with the new guidelines that were classified as "unlikely to have CF" in the previous guidelines. 8 (32%) patients with CFTR gene testing were positive for CFTR gene mutation(s). 4 (50%) of these patients were identified to have 2 CFTR mutations. One had variant combination that was reported to cause CF but all were diagnosed with CFTR-related metabolic syndrome. Our findings concur with the new CF diagnosis guidelines that changing the intermediate cut-off to 30-59 mmol/L sweat chloride concentration in combination with CFTR genetic analysis enhances the probability of identifying individuals that have risk of developing CF or have CF and enables for earlier therapeutic intervention.

Wind and boundary layers in Rayleigh-Bénard convection. II. Boundary layer character and scaling.

PubMed

van Reeuwijk, Maarten; Jonker, Harm J J; Hanjalić, Kemo

2008-03-01

The scaling of the kinematic boundary layer thickness lambda(u) and the friction factor C(f) at the top and bottom walls of Rayleigh-Bénard convection is studied by direct numerical simulation (DNS). By a detailed analysis of the friction factor, a new parameterisation for C(f) and lambda(u) is proposed. The simulations were made of an L/H=4 aspect-ratio domain with periodic lateral boundary conditions at Ra=(10(5), 10(6), 10(7), 10(8)) and Pr=1. The continuous spectrum, as well as significant forcing due to Reynolds stresses, clearly indicates a turbulent character of the boundary layer, while viscous effects cannot be neglected, judging from the scaling of classical integral boundary layer parameters with Reynolds number. Using a conceptual wind model, we find that the friction factor C(f) should scale proportionally to the thermal boundary layer thickness as C(f) proportional variant lambda(Theta)/H, while the kinetic boundary layer thickness lambda(u) scales inversely proportionally to the thermal boundary layer thickness and wind Reynolds number lambda(u)/H proportional variant (lambda(Theta)/H)(-1)Re(-1). The predicted trends for C(f) and lambda(u) are in agreement with DNS results.

Brittleness index of machinable dental materials and its relation to the marginal chipping factor.

PubMed

Tsitrou, Effrosyni A; Northeast, Simon E; van Noort, Richard

2007-12-01

The machinability of a material can be measured with the calculation of its brittleness index (BI). It is possible that different materials with different BI could produce restorations with varied marginal integrity. The degree of marginal chipping of a milled restoration can be estimated by the calculation of the marginal chipping factor (CF). The aim of this study is to investigate any possible correlation between the BI of machinable dental materials and the CF of the final restorations. The CEREC system was used to mill a wide range of materials used with that system; namely the Paradigm MZ100 (3M/ESPE), Vita Mark II (VITA), ProCAD (Ivoclar-Vivadent) and IPS e.max CAD (Ivoclar-Vivadent). A Vickers Hardness Tester was used for the calculation of BI, while for the calculation of CF the percentage of marginal chipping of crowns prepared with bevelled marginal angulations was estimated. The results of this study showed that Paradigm MZ100 had the lowest BI and CF, while IPS e.max CAD demonstrated the highest BI and CF. Vita Mark II and ProCAD had similar BI and CF and were lying between the above materials. Statistical analysis of the results showed that there is a perfect positive correlation between BI and CF for all the materials. The BI and CF could be both regarded as indicators of a material's machinability. Within the limitations of this study it was shown that as the BI increases so does the potential for marginal chipping, indicating that the BI of a material can be used as a predictor of the CF.

Interaction between Short-Term Heat Pretreatment and Fipronil on 2nd Instar Larvae of Diamondback Moth, Plutella Xylostella (Linn)

PubMed Central

Gu, Xiaojun; Tian, Sufen; Wang, Dehui; Gao, Fei; Wei, Hui

2010-01-01

Based on the cooperative virulence index (c.f.) and LC50 of fipronil, the interaction effect between short-term heat pretreatment and fipronil on 2nd instar larvae of diamondback moth (DBM), Plutella xylostella (Linnaeus), was assessed. The results suggested that pretreatment of the tested insects at 30 °C for 2, 4 and 8h could somewhat decrease the toxicity of fipronil at all set concentrations. The LC50 values of fipronil increased after heat pretreatment and c.f. values in all these treatments were below zero. These results indicated that real mortalities were less than theoretical ones and antagonism was found in the treatments of fipronil at 0.39 and 0.78 mg/L after heat pretreatment at 30 °C at 2, 4 and 8 h. However, pretreatment at 30 °C for 12h could increase the toxicity of fipronil at all set concentrations, the LC50 of fipronil decreased after heat pretreatment and c.f. values in all these treatments were above zero, which indicated real mortalities were higher than theoretical ones. Pretreatment of the tested insects at 35 °C for 2, 4, 8 and 12h was found to increase the toxicity of fipronil at all set concentrations which resulted in the decrease of LC50 values of fipronil and c.f. above zero in all treatments with only one exception. Most interactions were assessed as synergism. The results indicated that cooperative virulence index (c.f.) may be adopted in hormetic effect assessment. PMID:20877489

Calmodulin and calmodulin-binding proteins in cystic fibrosis and normal human fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tallant, E.A.; Wallace, R.W.

1986-05-01

The authors have investigated the possibility that a lesion in a calmodulin (CaM)-dependent regulatory mechanism may be involved in cystic fibrosis (CF). The level of CaM, CaM-binding proteins (CaM-BP) and a CaM-dependent phosphatase (CaM-Ptase) have been compared in cultured fibroblasts from CF patients versus age- and sex-matched control subjects. The CaM concentration, measured by radioimmunoassay, ranged from 0.20 to 0.76 ..mu..g/mg protein (n=8); there was no significant difference in the average CaM concentration from CF patients vs controls. Using Western blotting techniques with /sup 125/I-CaM, they detected at least ten distinct CaM-BPs in fibroblasts with molecular weights ranging from 230Kmore » to 37K; the only consistent difference between control and CF cell lines was in a 46.5K CaM-BP, which was depressed in all three CF samples. The 46.5 K CaM-BP was found only in the particulate fraction. A 59K CaM-BP was identified as a CaM-Ptase by its crossreactivity with an antibody against a brain CaM-Ptase. There was no significant difference in CaM-Ptase activity or in the amount of the phosphatase as determined by radioimmunoassay in CF vs. normal samples (n=8). Thus, the level of CaM as well as its various enzymes and proteins do not appear to be altered in CF fibroblasts except for a CaM-BP of 46.5K, the identity of which is currently being investigated.« less

Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets.

PubMed

Sun, Xingshen; Olivier, Alicia K; Yi, Yaling; Pope, Christopher E; Hayden, Hillary S; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T; Keiser, Nicholas W; Song, Yi; Tyler, Scott R; Goeken, J Adam; Kinyon, Joann M; Radey, Matthew C; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J; Kaminsky, Paul M; Brittnacher, Mitchell J; Miller, Samuel I; Parekh, Kalpaj; Meyerholz, David K; Hoffman, Lucas R; Frana, Timothy; Stewart, Zoe A; Engelhardt, John F

2014-05-01

Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

PubMed

Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

2016-10-01

Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Relationship between photosynthetic pigments and chlorophyll fluorescence in soybean under varying phosphorus nutrition at ambient and elevated CO2

USDA-ARS?s Scientific Manuscript database

Photosynthetic pigments such as chlorophyll (Chl) a, Chl b and carotenoids concentration, and chlorophyll fluorescence (CF) have widely been used as indicators of stress and photosynthetic performance in plants. Although photosynthetic pigments and CF are partly interdependent due to absorption and ...

Practices to Reduce Milk Carbon Footprint on Grazing Dairy Farms in Southern Uruguay: Case Studies.

USDA-ARS?s Scientific Manuscript database

Carbon footprint (CF) is an increasingly relevant indicator to estimate the impact of a product on climate change. This study followed international guidelines to quantify the CF of milk produced on 24 dairy farms in Uruguay. Cows were grazed all year and supplemented with concentrate feeds. These d...

Hexamethyldisilazane Removal with Mesoporous Materials Prepared from Calcium Fluoride Sludge.

PubMed

Kao, Ching-Yang; Lin, Min-Fa; Nguyen, Nhat-Thien; Tsai, Hsiao-Hsin; Chang, Luh-Maan; Chen, Po-Han; Chang, Chang-Tang

2018-05-01

A large amount of calcium fluoride sludge is generated by the semiconductor industry every year. It also requires a high amount of fuel consumption using rotor concentrators and thermal oxidizers to treat VOCs. The mesoporous adsorbent prepared by calcium fluoride sludge was used for VOCs treatment. The semiconductor industry employs HMDS to promote the adhesion of photo-resistant material to oxide(s) due to the formation of silicon dioxide, which blocks porous adsorbents. The adsorption of HMDS (Hexamethyldisiloxane) was tested with mesoporous silica materials synthesized from calcium fluoride (CF-MCM). The resulting samples were characterized by XRD, XRF, FTIR, N2-adsorption-desorption techniques. The prepared samples possessed high specific surface area, large pore volume and large pore diameter. The crystal patterns of CF-MCM were similar with Mobil composite matter (MCM-41) from TEM image. The adsorption capacity of HMDS with CF-MCM was 40 and 80 mg g-1, respectively, under 100 and 500 ppm HMDS. The effects of operation parameters, such as contact time and mixture concentration, on the performance of CF-MCM were also discussed in this study.

Cell-free DNA testing after combined test: factors affecting the uptake.

PubMed

Maiz, Nerea; Alzola, Irune; Murua, Emerson J; Rodríguez Santos, Javier

2016-11-01

First, to assess what was the uptake of cell free DNA (cfDNA) testing after a combined test and the maternal and fetal factors that influenced this decision, and second, to assess the uptake and factors that influence the choice of invasive testing. This observational retrospective study included 1083 singleton pregnancies who had a combined test for screening for Down syndrome between 11 (+) (0) and 13 (+) (6) weeks. Multivariate logistic regression analysis was used to determine which factors affected the uptake of cfDNA test and invasive testing among risk for trisomies 21, 18, and 13, maternal characteristics and fetal nuchal translucency (NT) thickness. Two-hundred fifty-seven (23.7%) women had a cfDNA test, 89 (8.2%) had an invasive test, and 737 (68.1%) had no further test. The uptake of cfDNA increased with the risk for trisomies (p < 0.001), maternal age (p = 0.013), and was higher in nulliparous women (p = 0.004). The uptake of invasive test increased with the risk for trisomies (p < 0.001) and NT thickness (p < 0.001). This study shows that the uptake of cfDNA testing increases with the risk for trisomies, maternal age, and is higher in nulliparous, whereas the uptake of invasive testing increases with the risk for trisomies and NT thickness.

A study on characteristic of different sample pretreatment methods to evaluate the entrapment efficiency of liposomes.

PubMed

Ran, Congcong; Chen, Dan; Xu, Meng; Du, Chaohui; Li, Qinglian; Jiang, Ye

2016-08-15

To examine how methods affect the evaluation of entrapment efficiency (EE) of liposomes, four different sample pretreatment methods were adopted in the experiment. The four sample pretreatment methods were size-exclusion chromatography (SEC), solid-phase extraction (SPE), centrifugation ultrafiltration (CF-UF) and hollow fiber centrifugal ultrafiltration (HF-CF-UF). Amphotericin B (AmB), which could self-associate to form aggregates in water is adopted as the model drugs in this paper. In the present work, it was found that the characterization results of four methods were quite different. The EE of liposome by SEC was about 93%, only 5-13% using C18 or HLB columns, and approximately 100% by CF-UF. The EE of HF-CF-UF reached up to nearly 99.0%. Further, this paper revealed the reasons making the difference of EE among four methods. Conventional SEC may distort the authentic of EE of liposomes with mainly employing some small liposomes or excessive water as eluent. For SPE, cholesterol on liposome surface could interact with the stationary phase making it hard to elute with water, and increase the risk of liposome leakage. While for CF-UF, concentration polarization was a main limitation hindering unentrapped drug to pass through membrane, making unentrapped drug undetectable in liposome. HF-CF-UF could truly reflect EE of liposomes with the concentration of unentrapped AmB lower than 25.0μg/mL. However, when the concentration was higher than 25.0μg/mL, AmB aggregates could be entrapped by hollow fiber. From the above analysis, this paper came to the conclusion that each method had its own feature in characterization. This study provided a reasonable guideline for choosing methods to character the EE of liposome. Copyright © 2016 Elsevier B.V. All rights reserved.

Improvement of the fracture toughness of hydroxyapatite (HAp) by incorporation of carboxyl functionalized single walled carbon nanotubes (CfSWCNTs) and nylon

DOE PAGES

Khanal, Suraj P.; Mahfuz, Hassan; Rondinone, Adam Justin; ...

2015-11-12

The potential of improving the fracture toughness of synthetic hydroxyapatite (HAp) by incorporating carboxyl functionalized single walled carbon nanotubes (CfSWCNTs) and polymerized ε-caprolactam (nylon) was researched. A series of HAp samples with CfSWCNTs concentrations varying from 0 to 1.5 wt.%, without, and with nylon addition was prepared. X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM) were used to characterize the samples. The three point bending test was applied to measure the fracture toughness of the composites. A reproducible value of 3.6 ± 0.3 MPa.√m was found for samples containing 1 wt.% CfSWCNTs and nylon. This valuemore » is in the range of the cortical bone fracture toughness. Lastly, the increase of the CfSWCNTs content results to decrease of the fracture toughness, and formation of secondary phases.« less

Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA.

PubMed

Zemmour, Hai; Planer, David; Magenheim, Judith; Moss, Joshua; Neiman, Daniel; Gilon, Dan; Korach, Amit; Glaser, Benjamin; Shemer, Ruth; Landesberg, Giora; Dor, Yuval

2018-04-24

Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development.

Cystic fibrosis: terminology and diagnostic algorithms

PubMed Central

De Boeck, K; Wilschanski, M; Castellani, C; Taylor, C; Cuppens, H; Dodge, J; Sinaasappel, M

2006-01-01

There is great heterogeneity in the clinical manifestations of cystic fibrosis (CF). Some patients may have all the classical manifestations of CF from infancy and have a relatively poor prognosis, while others have much milder or even atypical disease manifestations and still carry mutations on each of the CFTR genes. It is important to distinguish between these categories of patients. The European Diagnostic Working Group proposes the following terminology. Patients are diagnosed with classic or typical CF if they have one or more phenotypic characteristics and a sweat chloride concentration of >60 mmol/l. The vast majority of CF patients fall into this category. Usually one established mutation causing CF can be identified on each CFTR gene. Patients with classic CF can have exocrine pancreatic insufficiency or pancreatic sufficiency. The disease can have a severe course with rapid progression of symptoms or a milder course with very little deterioration over time. Patients with non‐classic or atypical CF have a CF phenotype in at least one organ system and a normal (<30 mmol/l) or borderline (30–60 mmol/l) sweat chloride level. In these patients confirmation of the diagnosis of CF requires detection of one disease causing mutation on each CFTR gene or direct quantification of CFTR dysfunction by nasal potential difference measurement. Non‐classic CF includes patients with multiorgan or single organ involvement. Most of these patients have exocrine pancreatic sufficiency and milder lung disease. Algorithms for a structured diagnostic process are proposed. PMID:16384879

Cystic fibrosis: terminology and diagnostic algorithms.

PubMed

De Boeck, K; Wilschanski, M; Castellani, C; Taylor, C; Cuppens, H; Dodge, J; Sinaasappel, M

2006-07-01

There is great heterogeneity in the clinical manifestations of cystic fibrosis (CF). Some patients may have all the classical manifestations of CF from infancy and have a relatively poor prognosis, while others have much milder or even atypical disease manifestations and still carry mutations on each of the CFTR genes. It is important to distinguish between these categories of patients. The European Diagnostic Working Group proposes the following terminology. Patients are diagnosed with classic or typical CF if they have one or more phenotypic characteristics and a sweat chloride concentration of >60 mmol/l. The vast majority of CF patients fall into this category. Usually one established mutation causing CF can be identified on each CFTR gene. Patients with classic CF can have exocrine pancreatic insufficiency or pancreatic sufficiency. The disease can have a severe course with rapid progression of symptoms or a milder course with very little deterioration over time. Patients with non-classic or atypical CF have a CF phenotype in at least one organ system and a normal (<30 mmol/l) or borderline (30-60 mmol/l) sweat chloride level. In these patients confirmation of the diagnosis of CF requires detection of one disease causing mutation on each CFTR gene or direct quantification of CFTR dysfunction by nasal potential difference measurement. Non-classic CF includes patients with multiorgan or single organ involvement. Most of these patients have exocrine pancreatic sufficiency and milder lung disease. Algorithms for a structured diagnostic process are proposed.

Compassion fatigue, burnout and compassion satisfaction among family physicians in the Negev area - a cross-sectional study.

PubMed

El-Bar, Nurit; Levy, Amalia; Wald, Hedy S; Biderman, Aya

2013-08-15

Compassion fatigue among health care professionals has gained interest over the past decade. Compassion fatigue, as well as burnout, has been associated with depersonalization and suboptimal patient care. Professional caregivers in general are exposed to the risk of compassion fatigue (CF), burnout (BO) and low levels of compassion satisfaction (CS). While CF has been studied in health care professionals, few publications address its incidence among family physicians, specifically. The objectives of this study were to assess the prevalence and severity of CF among family practitioners (FPs) in the Negev (Israel's southern region), evaluating the correlations between CF, BO and CS and their relations with socio-demographic variables and work related characteristics. Self-report anonymous Compassion Satisfaction and Fatigue Test questionnaires (CSFT) measuring CF, BO, and CS were distributed among 194 family physicians at Clalit Health Services clinics in the Negev between July 2007 and April 2008. Correlations between CF, BO and CS were assessed. Multivariable logistic regression models with backward elimination were constructed. 128 (66%) physicians responded. 46.1% of respondents scored extremely high and high for CF, 21.1% scored low for CS and 9.4% scored high for BO. Strong correlations were found between BO and CF (r = 0.769, p < 0.001), and between BO and CS (r = -0.241, p = 0.006), but no correlation was found between CS and CF. The logistic regression model showed that the only factor associated with a significantly increased risk for CF was former immigration to Israel. Increased risk for BO was associated with female gender, history of personal trauma and lack of academic affiliation. Higher CS was associated with holding management positions and teaching residents. Family physicians in the Negev are at high risk for CF, with the potential for CF- associated patient dissatisfaction, compromised patient safety and increased medical error. We propose creation of a CF educational and early intervention treatment program for family physicians and other health care professionals. Such programs would train facilitators of physician well-being and resiliency building. We also recommend analyzing contributing variables and organizational factors related to higher CF. Policy recommendations include integrating such programs within required risk management continuing medical education.

Compassion fatigue, burnout and compassion satisfaction among family physicians in the Negev area - a cross-sectional study

PubMed Central

2013-01-01

Background Compassion fatigue among health care professionals has gained interest over the past decade. Compassion fatigue, as well as burnout, has been associated with depersonalization and suboptimal patient care. Professional caregivers in general are exposed to the risk of compassion fatigue (CF), burnout (BO) and low levels of compassion satisfaction (CS). While CF has been studied in health care professionals, few publications address its incidence among family physicians, specifically. The objectives of this study were to assess the prevalence and severity of CF among family practitioners (FPs) in the Negev (Israel’s southern region), evaluating the correlations between CF, BO and CS and their relations with socio-demographic variables and work related characteristics. Methods Self-report anonymous Compassion Satisfaction and Fatigue Test questionnaires (CSFT) measuring CF, BO, and CS were distributed among 194 family physicians at Clalit Health Services clinics in the Negev between July 2007 and April 2008. Correlations between CF, BO and CS were assessed. Multivariable logistic regression models with backward elimination were constructed. Results 128 (66%) physicians responded. 46.1% of respondents scored extremely high and high for CF, 21.1% scored low for CS and 9.4% scored high for BO. Strong correlations were found between BO and CF (r = 0.769, p < 0.001), and between BO and CS (r = −0.241, p = 0.006), but no correlation was found between CS and CF. The logistic regression model showed that the only factor associated with a significantly increased risk for CF was former immigration to Israel. Increased risk for BO was associated with female gender, history of personal trauma and lack of academic affiliation. Higher CS was associated with holding management positions and teaching residents. Conclusions and policy recommendations Family physicians in the Negev are at high risk for CF, with the potential for CF- associated patient dissatisfaction, compromised patient safety and increased medical error. We propose creation of a CF educational and early intervention treatment program for family physicians and other health care professionals. Such programs would train facilitators of physician well-being and resiliency building. We also recommend analyzing contributing variables and organizational factors related to higher CF. Policy recommendations include integrating such programs within required risk management continuing medical education. PMID:23947591

42 CFR 414.28 - Conversion factors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Practitioners § 414.28 Conversion factors. CMS establishes CFs in accordance with section 1848(d) of the Act. (a) Base-year CFs. CMS established the CF for 1992 so that had section 1848 of the Act applied during 1991... in § 414.30. (b) Subsequent CFs. For calendar years 1993 through 1995, the CF for each year is equal...

Density fluctuations in aqueous solution of ionic liquid with lower critical solution temperature: Mixture of tetrabutylphosphonium trifluoroacetate and water

NASA Astrophysics Data System (ADS)

Nitta, Ayako; Morita, Takeshi; Saita, Shohei; Kohno, Yuki; Ohno, Hiroyuki; Nishikawa, Keiko

2015-05-01

Aqueous solutions of tetrabutylphosphonium trifluoroacetate ([P4444]CF3COO) exhibit a LCST-type phase transition with the critical point near 0.025 in mole fraction of [P4444]CF3COO at T = 302 K. The phase behavior of [P4444]CF3COO-water mixtures was investigated by evaluating their density fluctuations, which provide quantitative descriptions of the mixing states of the solutions. The concentration dependence of the density fluctuations was investigated at 293 and 301 K for the mixtures without distinguishing the components and for the individual components ([P4444]CF3COO and water). A drastic change in the mixing state was observed for the solution when the critical point was approached.

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

PubMed Central

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Effects at early stage of life of elevated milk replacer feeding on growth rate, plasma IGF-I concentration and intestinal nutrient transporter expression in Holstein bull calves.

PubMed

Orihashi, Takenori; Mashiko, Takanori; Sera, Kenji; Roh, Sang-Gun; Katoh, Kazuo; Obara, Yoshiaki

2012-01-01

In order to evaluate the effects of an elevated amount of modified milk replacer on body weight, daily gain, starter intake, plasma endocrine parameters and expression of nutrient transporters in small intestinal epithelia, Holstein bull calves (n=24) were fed for 60days either with the usual amount of 24% crude protein (CP) and 20% fat milk (CF) replacer (C group), or with a double amount of a modified milk replacer of 28% CP and 16% CF (E group). Body weight from D20 to D60 and daily gain before D40 was greater or tended to be greater for the E group than the C group. Plasma concentrations of insulin-like growth factor-1 (IGF-I) and insulin were greater for the E group than the C group on D28 but not on D56, without changing plasma growth hormone levels. Gene expression for sodium-dependent glucose transporter 1 and fatty acid translocase (CD36) was altered in day- and intestine-dependent manners. From these findings, we conclude that an elevated intake of milk replacer given up to 40days old is sufficient to enhance body weight, which may be associated with increased plasma IGF-I concentrations, in Holstein bulls. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.

PubMed

Andrén Aronsson, Carin; Uusitalo, Ulla; Vehik, Kendra; Yang, Jimin; Silvis, Katherine; Hummel, Sandra; Virtanen, Suvi M; Norris, Jill M

2015-10-01

Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self-reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later. © 2013 John Wiley & Sons Ltd.

Using a simulation model to assess risk of false negative point-of-care urinary human chorionic gonadotropin device results due to high-dose hook interference.

PubMed

Milhorn, Denise; Korpi-Steiner, Nichole

2015-02-01

It is unclear if the point-of-care (POC) Clinitest hCG device is subject to high-dose hook interference from physiological concentrations of intact human chorionic gonadotropin (hCG), β-core fragment of hCG (hCGβcf), and hCG free β-subunit (hCGβ) found in urine during pregnancy. We used a simulation model to address this question and related our findings to our institution's pregnant population in order to assess risk for potential false-negative hCG results. The expected distribution of days relative to ovulation during routine POC hCG testing was estimated from 182 patients. Clinitest-Clinitek Status hCG device susceptibility to high-dose hook interference from hCG variants and potential risk of false-negative results as it relates to this population were evaluated by testing increasing concentrations of hCG, hCGβcf, hCGβ as well as urine simulating physiological hCG, hCGβcf and hCGβ concentrations expected during early pregnancy (≤44 days post-ovulation). The Clinitest-Clinitek Status hCG device exhibited high-dose hook interference from hCGβcf alone, but not from hCG, hCGβ, or simulated physiological urinary concentrations of combined hCG, hCGβcf and hCGβ expected during early pregnancy. The majority of our patient population had urinary hCG testing conducted during early pregnancy. The Clinitest-Clinitek Status hCG device is unlikely to exhibit false-negative urinary hCG results due to high-dose hook interference for women in early healthy pregnancy, although additional studies are necessary to determine potential risk in other patient populations. Visual interpretation of POC urinary hCG device results is an important failure mode to consider in risk analyses for erroneous urinary hCG device results. Published by Elsevier Inc.

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

PubMed

Maitra, Rangan; Porter, Melissa A; Huang, Shan; Gilmour, Brian P

2009-05-13

Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL-8 measurements and high-content fluorescent imaging of NFkappaB subunit p65 translocation. Since the airways of CF patients can be specifically targeted for delivery of therapeutics, we propose that WFA should be further studied as an anti-inflammatory agent in models of CF related inflammation mediated by NFkappaB.

Serial perioperative cell-free DNA levels in donors and recipients undergoing living donor liver transplantation.

PubMed

Prakash, K; Aggarwal, S; Bhardwaj, S; Ramakrishna, G; Pandey, C K

2017-10-01

Effect of anaesthesia and surgery on cell-free DNA (cfDNA) is not known. Given that surgical stress augments inflammation and injury, we hypothesized that levels of cfDNA will fluctuate during perioperative period. Therefore, in this study serial perioperative cfDNA concentration was measured in donors and recipients undergoing living donor liver transplantation (LDLT). Baseline, post-induction, intraoperative and post-operative plasma cfDNA levels were evaluated in 21 donors and recipients each, by Sytox green method. In addition, qPCR was performed in a subset of samples. Baseline cfDNA levels were higher in recipients (37.62 ng/ml) than in donors (25.49 ng/ml). A decrease in cfDNA was observed following anaesthesia induction in both recipients (11.90 ng/ml) and donors (10.75 ng/ml). When the kinetics of the cfDNA was monitored further, an increase was noted intraoperatively in donors (46.18 ng/ml) and recipients (anhepatic phase: 56.25 ng/ml, reperfusion phase: 54.36 ng/ml). cfDNA levels remained high post-operatively. One recipient who developed post-operative sepsis had the highest cfDNA level (94.72 ng/ml). Plasma cfDNA levels are high in recipients indicative of liver injury. Lower cfDNA levels following induction may be attributed to the subduing effect of anaesthetic agents on cell death. High cfDNA levels seen in intra- and post-operative phases reflect cellular trauma and inflammation. This similar pattern of fluctuation of cfDNA level in donors and recipients is suggestive of its possible utility as a surgical stress marker. In addition, comparable cfDNA levels in anhepatic and reperfusion phase reflect less ischemia reperfusion injury during LDLT. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Carotid femoral pulse wave velocity in type 2 diabetes and hypertension: capturing arterial health effects of step counts

PubMed Central

Dasgupta, Kaberi; Rosenberg, Ellen; Joseph, Lawrence; Trudeau, Luc; Garfield, Natasha; Chan, Deborah; Sherman, Mark; Rabasa-Lhoret, Rémi; Daskalopoulou, Stella S.

2017-01-01

Objective: Optimal medication use obscures the impact of physical activity on traditional cardiometabolic risk factors. We evaluated the relationship between step counts and carotid-femoral pulse wave velocity (cfPWV), a summative risk indicator, in patients with type 2 diabetes and/or hypertension. Research design and methods: Three hundred and sixty-nine participants were recruited (outpatient clinics; Montreal, Quebec; 2011–2015). Physical activity (pedometer/accelerometer), cfPWV (applanation tonometry), and risk factors (A1C, Homeostatic Model Assessment–Insulin Resistance, blood pressure, lipid profiles) were evaluated. Linear regression models were constructed to quantify the relationship of steps/day with cfPWV. Results: The study population comprised 191 patients with type 2 diabetes and hypertension, 39 with type 2 diabetes, and 139 with hypertension (mean ± SD: age 59.6 ± 11.2 years; BMI 31.3 ± 4.8 kg/m2; 54.2% women). Blood pressure (125/77 ± 15/9 mmHg), A1C (diabetes: 7.7 ± 1.3%; 61 mmol/mol), and low-density lipoprotein cholesterol (diabetes: 2.19 ± 0.8 mmol/l; without diabetes: 3.13 ± 1.1mmol/l) were close to target. Participants averaged 5125 ± 2722 steps/day. Mean cfPWV was 9.8 ± 2.2 m/s. Steps correlated with cfPWV, but not with other risk factors. A 1000 steps/day increment was associated with a 0.1 m/s cfPWV decrement across adjusted models and in subgroup analysis by diabetes status. In a model adjusted for age, sex, BMI, ethnicity, immigrant status, employment, education, diabetes, hypertension, medication classes, the mean cfPWV decrement was 0.11 m/s (95% confidence interval −0.2, −0.02). Conclusions: cfPWV is responsive to step counts in patients who are well controlled on cardioprotective medications. This ability to capture the ‘added value’ of physical activity supports the emerging role of cfPWV in arterial health monitoring. PMID:28129250

Unstimulated Saliva-Related Caries Risk Factors in Individuals with Cystic Fibrosis: A Cross-Sectional Analysis of Unstimulated Salivary Flow, pH, and Buffering Capacity.

PubMed

Alkhateeb, Alaa A; Mancl, Lloyd A; Presland, Richard B; Rothen, Marilynn L; Chi, Donald L

2017-01-01

Salivary flow rate, pH, and buffering capacity are associated with dental caries, but studies from the cystic fibrosis (CF) literature are inconclusive regarding these salivary factors and caries. The aim of this study was to evaluate these factors and their associations with dental caries in individuals with CF. Unstimulated whole saliva was collected from individuals aged 6-20 years at Seattle Children's Hospital CF Clinic, USA (n = 83). Salivary flow rate was measured in milliliters per minute. Salivary pH was assessed using a laboratory pH meter. Buffering capacity was assessed by titration with HCl. The outcome measure was caries prevalence, defined as the number of decayed, missing, or filled primary and permanent tooth surfaces. Spearman's rank correlation coefficient and the t test were used to test for bivariate associations. Multiple variable linear regression models were used to (1) run confounder-adjusted analyses and (2) assess for potential interactions. There was no significant association between salivary flow rate or buffering capacity and caries prevalence. There was a significant negative association between salivary pH and caries prevalence, but this association was no longer significant after adjusting for age. There was no significant interaction between salivary flow rate and buffering capacity or between antibiotic use and the 3 salivary factors. Our results indicate that unstimulated salivary factors are not associated with dental caries prevalence in individuals with CF. Future studies should investigate other potential saliva-related caries risk factors in individuals with CF such as cariogenic bacteria levels, salivary host defense peptide levels, and medication use. © 2016 S. Karger AG, Basel.

Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis.

PubMed

Hong, Gina; Psoter, Kevin J; Jennings, Mark T; Merlo, Christian A; Boyle, Michael P; Hadjiliadis, Denis; Kawut, Steven M; Lechtzin, Noah

2018-02-12

Aspergillus species are increasingly detected in the respiratory tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus fumigatus is associated with more frequent hospitalizations for pulmonary exacerbations. However, patient and clinical factors that may contribute to the acquisition of persistent Aspergillus infection have yet to be identified. The objective of this study was to identify risk factors for development of Aspergillus respiratory isolation in CF. A retrospective cohort study of participants in the CF Foundation Patient Registry between 2006 and 2012 was conducted. Generalized estimating equation models were used to evaluate the association between the development of persistent Aspergillus respiratory isolation and individual level demographic and clinical characteristics. Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95% confidence interval 1.23, 2.48, p<0.001) and pancreatic insufficiency (OR 1.50, 95% CI 1.09, 2.06, p<0.001) were found to be risk factors for persistent Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33; 95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p<0.001), and inhaled corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p<0.001) were also independently associated with an increased risk for persistent Aspergillus isolation. We identified macrolides and inhaled antibiotics, which individually have been shown to improve CF outcomes, and inhaled corticosteroids as risk factors for developing persistent Aspergillus isolation. Further work is needed to determine whether these associations are causal or due to confounding by other factors. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Factors affecting nebulised medicine adherence in adult patients with cystic fibrosis: a qualitative study.

PubMed

Hogan, Alice; Bonney, Mary-Ann; Brien, Jo-Anne; Karamy, Rita; Aslani, Parisa

2015-02-01

Nebulised medicines contribute to the high treatment burden experienced by patients with cystic fibrosis (CF). This study explored experiences of adult patients with CF when using nebulised medicines, factors impacting on their adherence to nebulised therapy and strategies they used to facilitate adherence. Community setting, in Sydney, Australia. Ten patients with CF were recruited through a CF patient organisation. Semi-structured face-to-face interviews were conducted, addressing the study objectives. Interviews were audio-recorded, transcribed verbatim and content analysed for anticipated and emergent themes. Experiences with using nebulised medicines; and barriers and facilitators of adherence to nebulised medicines. Participants' age ranged from 22 to 45 years, with half being male. Four broad themes (with more specific sub-themes) were identified from the interviews: experiences with using nebulised medicines (cleaning nebuliser, time taken to use nebuliser medicine, flexibility in use of nebuliser); feelings about using nebulised medicines (necessary/important, dislike, part of life); factors impacting non-adherence (time consuming therapy, side effects/effects of medicine, work/social demands, lack of perceived importance); factors and strategies facilitating adherence (perceived medicine importance, habit/routine, support, health benefits, technology/medicine dose form, timetabling). Nebulised therapy for cystic fibrosis patients takes a substantial amount of time, with patients trying to alter their routine to incorporate nebulising into their daily lives. However there are still many factors that lead to low adherence, including work/social demands and travelling. Patients balance the necessity for nebulised therapy against the barriers, and engage in intentional non-adherence at times. Future strategies and resources should target and address specific factors identified by patients with CF as being important and impacting their adherence to nebulised medicines.

A study of disequilibrium between 220Rn and 216Po for 220Rn measurements using a flow-through Lucas scintillation cell.

PubMed

Sathyabama, N; Datta, D; Gaware, J J; Mayya, Y S; Tripathi, R M

2014-01-01

Lucas-type scintillation cells (LSCs) are commonly used for rapid measurements of (220)Rn concentrations in flow-through mode in field and for calibration experiments in laboratories. However, in those measurements, equilibrium between (220)Rn and (216)Po is generally assumed and two alpha particles are considered to be emitted per (220)Rn decay due to very short half-life of (216)Po. In this paper, a small, yet significant disequilibrium existing between (220)Rn and (216)Po has been examined and shown that less than two alpha particles are actually emitted per (220)Rn decay in the cell when flow is maintained. A theoretical formula has been derived for the first time for a correction factor (CF) to be applied to this measured concentration to account for the disequilibrium. The existence of this disequilibrium has been verified experimentally and is found to increase with the increase in the ratio of flow rate to cell volume. The reason for the disequilibrium is attributed to the flushing out of (216)Po formed in the cell before its decay due to the flow. Uncertainties in measured concentrations have been estimated and the estimated CF values have been found to be significant for the flow rates considered above 5 dm(3) min(-1) for a cell of volume 0.125 dm(3). The calculated values of the CF are about 1.055 to 1.178 in the flow rate range of 4 to 15 dm(3) min(-1) for the cell of volume 0.125 dm(3), while the corresponding experimental values are 1.023 to 1.264. This is a systematic error introduced in (220)Rn measurements using a flow-through LSC, which can be removed either by correct formulation or by proper design of a measurement set-up.

Aureobasidium pullulans produced β-glucan is effective to enhance Kurosengoku soybean extract induced Thrombospondin-1 expression.

PubMed

Muramatsu, Daisuke; Okabe, Mitsuyasu; Takaoka, Akinori; Kida, Hiroshi; Iwai, Atsushi

2017-06-06

Black yeast, Aureobasidium pullulans is extracellularly produced β-(1,3), (1,6)-D-glucan (β-glucan) under certain conditions. In this study, using Glycine max cv. Kurosengoku (Kurosengoku soybeans), the production of β-glucan through fermentation of A. pullulans was evaluated, and the effects of A. pullulans cultured fluid (AP-CF) containing β-glucan made with Kurosengoku soybeans (kAP-CF) on a human monocyte derived cell line, Mono Mac 6 cells were investigated. Concentration of β-glucan in kAP-CF reached the same level as normal AP-CF. An anti-angiogenic protein, Thrombospondin-1 (THBS1) was effectively induced after the stimulation with kAP-CF for comparison with AP-CF. The THBS1 is also induced after stimulation with hot water extract of Kurosengoku soybeans (KS-E), while the combined stimulation of β-glucan with KS-E more effectively induced THBS1 than that with KS-E alone. These results suggest effects of A. pullulans-produced β-glucan on the enhancement of Kurosengoku soybean-induced THBS1 expression.

Coral calcifying fluid pH is modulated by seawater carbonate chemistry not solely seawater pH.

PubMed

Comeau, S; Tambutté, E; Carpenter, R C; Edmunds, P J; Evensen, N R; Allemand, D; Ferrier-Pagès, C; Tambutté, S; Venn, A A

2017-01-25

Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pH CF ) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pH CF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (A T ). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pH CF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [A T ], revealing that seawater pH is not the sole driver of pH CF Notably, when we synthesize our results with published data, we identify linear relationships of pH CF with the seawater [DIC]/[H + ] ratio, [A T ]/ [H + ] ratio and [[Formula: see text

Adsorption and photocatalytic degradation of 2-CP in wastewater onto CS/CoFe₂O ₄ nanocomposite synthesized using gamma radiation.

PubMed

Taleb, Manal F Abou

2014-12-19

Photocatalytic degradation of 2-chlorophenol (2-CP) was studied using the photocatalyst chitosane/CoFe2O4 nanocomposite (CS/CF) under visible light. CS/CF nanocomposites were synthesized via gamma irradiation cross-linking method with the aid of sonication. Physical characteristics of CS/CF were studied using infrared spectrophotometer (IR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and ultraviolet-visible (UV-vis) spectroscopy. Their photocatalytic activity was tested for the degradation of 2-CP in aqueous medium using sunlight. The effect of different parameters such as catalyst concentration, 2-CP concentration and reaction pH on degradation was also examined. It was verified that the 2-CP degradation rate fits a pseudo-first-order kinetics for initial 2-CP concentrations between 25 and 100mg/l, at 30°C. The degradation kinetics fit well Langmuir-Hinshelwood rate law. The degradation of (2-CP) follows pseudo-first-order kinetics. Results showed that after the catalyst had been used 5 times repeatedly, the degradation rate was still above 80%. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disease-modifying genetic factors in cystic fibrosis.

PubMed

Marson, Fernando A L

2018-05-01

To compile data from the past 10 years regarding the role of modifying genes in cystic fibrosis (CF). CF is a model disease for understanding of the action of modifying genes. Although it is a monogenic (CFTR) autosomal recessive disease, CF presents with wide phenotypic variability. In CF, variability occurs with different intensity among patients by each organ, being organ-specific, resulting from the mutual interaction of environmental and genetic factors, including CFTR mutations and various other genes, most of which are associated with inflammatory processes. In individuals, using precision medicine, gene modification studies have revealed individualized responses to drugs depending on particular CFTR mutations and modifying genes, most of which are alternative ion channels. Studies of modifying genes in CF allow: understanding of clinical variability among patients with the same CFTR genotype; evaluation of precision medicine; understanding of environmental and genetic effects at the organ level; understanding the involvement of genetic variants in inflammatory responses; improvements in genetic counseling; understanding the involvement of genetic variants in inflammatory responses in lung diseases, such as asthma; and understanding the individuality of the person with the disease.

Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin.

PubMed

Keitsch, Simone; Riethmüller, Joachim; Soddemann, Matthias; Sehl, Carolin; Wilker, Barbara; Edwards, Michael J; Caldwell, Charles C; Fraunholz, Martin; Gulbins, Erich; Becker, Katrin Anne

2018-05-01

Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of α-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of α-toxin in JE2-Δhla reduced the pathogenicity of S. aureus in CF mice. However, CF mice were still more susceptible to the mutant S. aureus strain than wildtype mice. The S. aureus JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of α-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of α-toxin is a major factor causing S. aureus infections in CF mice. Wildtype S. aureus induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.

Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.

Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors ofmore » bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.« less

Coping styles in adults with cystic fibrosis: implications for emotional and social quality of life.

PubMed

Mc Hugh, Rachel; Mc Feeters, Danielle; Boyda, David; O'Neill, Siobhan

2016-01-01

As life expectancy increases, interest has grown surrounding the factors that may influence quality of life (QOL) for people with cystic fibrosis (CF). The aim of the current study was to examine which specific coping styles were positively or negatively associated with social and emotional QOL in a CF sample. One hundred and twenty-two respondents aged 18 and over were recruited through an online support group. Respondents completed the 'CF Questionnaire-Revised (CFQ-R)' and the 'Brief COPE'. The CFQ-R is a disease-specific instrument designed to measure the impact of CF on nine QOL domains and the Brief COPE is a 28 item questionnaire which assesses 14 coping scales. A multivariate regression model revealed that higher substance abuse and disengagement was associated with lower emotional QOL whereas greater use of religion, instrumental coping and acceptance was positively associated with emotional QOL. Active coping was linked to better social QOL and a negative association was reported between distraction coping with both emotional and social domains. Given the burden of CF, ascertaining which factors enhance or diminish emotion and social well-being is now an integral component of QOL research. The current findings may therefore have value in informing clinical interventions which aim to cater for the psychological needs of individuals with CF.

Fabrication of hierarchical ZnO nanostructures on cotton fabric for wearable device applications

NASA Astrophysics Data System (ADS)

Pandiyarasan, V.; Suhasini, S.; Archana, J.; Navaneethan, M.; Majumdar, Abhijit; Hayakawa, Y.; Ikeda, H.

2017-10-01

We have investigated ZnO nanostructures on cotton fabric (CF) s a flexible material for an application of wearable thermoelectric (TE) power generator which requires super-hydrophobicity, UV protection, and high TE efficiency. Field emission scanning electron microscopy images revealed that the formed ZnO nanostructures have a mixture of nanorods and nanosheets and are uniformly coated on the CF. XRD pattern and Raman spectra revealed that the ZnO nanostructure has a wurtzite structure. Contact angle measurements showed that the ZnO-nanostructures-coated CF possessed a high super hydrophobic nature with an angle of 132.5°. ZnO nanocomposite/CF sample exhibited an excellent UV protection factor 183.84. Seebeck coefficient, electrical resistivity and thermoelectric power factor of the ZnO nanostructures on cotton fabric were evaluated to be 28 μV/K, 0.04 Ω-cm, and 22 μW/m K2, respectively.

Compassion Fatigue and Psychological Distress Among Social Workers: A Validation Study

PubMed Central

Adams, Richard E.; Boscarino, Joseph A.; Figley, Charles R.

2009-01-01

Few studies have focused on caring professionals and their emotional exhaustion from working with traumatized clients, referred to as compassion fatigue (CF). The present study had 2 goals: (a) to assess the psychometric properties of a CF scale, and (b) to examine the scale's predictive validity in a multivariate model. The data came from a survey of social workers living in New York City following the September 11, 2001, terrorist attacks on the World Trade Center. Factor analyses indicated that the CF scale measured multiple dimensions. After overlapping items were eliminated, the scale measured 2 key underlying dimensions—secondary trauma and job burnout. In a multivariate model, these dimensions were related to psychological distress, even after other risk factors were controlled. The authors discuss the results in light of increasing the ability of professional caregivers to meet the emotional needs of their clients within a stressful environment without experiencing CF. PMID:16569133

Cost(s) of caring for patients with cystic fibrosis.

PubMed

Orenstein, David M; Abood, Robert N

2018-06-01

Cystic fibrosis (CF) has received a lot of attention in the past few years because of increased longevity and the emergence of ground-breaking new drugs targeting the molecular and cellular defects, making a huge clinical difference, and - not incidentally - carrying massive price tags. The prices of these new drugs make the question of overall costs of CF care highly relevant. This article reviews recent developments in CF science and treatment, and highlights areas that contribute to costs of CF care, emphasizing how these costs have increased. This article should help the pediatrician stay abreast of high points of CF care, with an awareness of the factors that wield the biggest influence on overall costs, to patients, families and the US healthcare system.

The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

PubMed Central

Sanchez-Dominguez, Celia N.; Reyes-Lopez, Miguel A.; Bustamante, Adriana; Cerda-Flores, Ricardo M.; Villalobos-Torres, Maria del C.; Gallardo-Blanco, Hugo L.; Rojas-Martinez, Augusto; Martinez-Rodriguez, Herminia G.; Barrera-Saldaña, Hugo A.; Ortiz-Lopez, Rocio

2014-01-01

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (−251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP. Results The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25–9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease. Conclusion An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients. PMID:24603877

Cat and Dog Exposure and Respiratory Morbidities in Cystic Fibrosis

PubMed Central

Morrow, Christopher B.; Raraigh, Karen S.; Green, Deanna M.; Blackman, Scott M.; Cutting, Garry R.; Collaco, Joseph M.

2014-01-01

Objective To understand the triggers that may impact respiratory health in cystic fibrosis (CF), including the effects of pets, because environmental factors contribute to one-half of the variation in lung function in patients with CF. Study design A total of 703 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of cats and dogs in households with a child with CF. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track respiratory and infection outcomes. Results Within the sample 47% of subjects reported owning a dog, and 28% reported owning a cat. After adjustment for demographic factors, dog ownership was not associated with any adverse clinical outcomes, and cat ownership was associated an increased risk in developing nasal polyps (adjusted OR 1.66; p=0.024) compared with non-cat owners. Subjects who owned both cats and dogs were twice as likely to report wheezing compared with other subjects (adjusted OR: 2.01; p=0.009). There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and non-cat/dog owners. Conclusions Cat ownership was associated with a higher frequency of developing nasal polyps and combined cat-dog ownership was associated with a higher rate of wheezing. Prospective studies are needed to confirm these associations and the potential psychosocial benefits of cat and/or dog ownership. PMID:25027361

Cat and dog exposure and respiratory morbidities in cystic fibrosis.

PubMed

Morrow, Christopher B; Raraigh, Karen S; Green, Deanna M; Blackman, Scott M; Cutting, Garry R; Collaco, Joseph M

2014-10-01

To understand the triggers that may impact respiratory health in cystic fibrosis (CF), including the effects of pets, because environmental factors contribute to one-half of the variation in lung function in patients with CF. A total of 703 subjects with CF were recruited through the US CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of cats and dogs in households with a child with CF. Questionnaires, chart review, and US CF Foundation Patient Registry data were used to track respiratory and infection outcomes. Within the sample, 47% of subjects reported owning a dog, and 28% reported owning a cat. After adjustment for demographic factors, dog ownership was not associated with any adverse clinical outcomes, and cat ownership was associated an increased risk in developing nasal polyps (aOR 1.66; P = .024) compared with noncat owners. Subjects who owned both cats and dogs were twice as likely to report wheezing compared with other subjects (aOR: 2.01; P = .009). There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and noncat/dog owners. Cat ownership was associated with a greater frequency of developing nasal polyps and combined cat-dog ownership was associated with a greater rate of wheezing. Prospective studies are needed to confirm these associations and the potential psychosocial benefits of cat and/or dog ownership. Copyright © 2014 Elsevier Inc. All rights reserved.

Two novel LRR-only proteins in Chlamys farreri: Similar in structure, yet different in expression profile and pattern recognition.

PubMed

Wang, Mengqiang; Wang, Lingling; Xin, Lusheng; Wang, Xiudan; Wang, Lin; Xu, Jianchao; Jia, Zhihao; Yue, Feng; Wang, Hao; Song, Linsheng

2016-06-01

Leucine-rich repeat (LRR)-only proteins could mediate protein-ligand and protein-protein interactions and be involved in the immune response. In the present study, two novel LRR-only proteins, CfLRRop-2 and CfLRRop-3, were identified and characterized from scallop Chlamys farreri. They both contained nine LRR motifs with the consensus signature sequence LxxLxLxxNxL and formed typical horseshoe structure. The CfLRRop-2 and CfLRRop-3 mRNA transcripts were constitutively expressed in haemocytes, muscle, mantle, gill, haepatopancreas and gonad, with the highest expression level in haepatopancreas and gill, respectively. During the ontogenesis of scallop, the mRNA transcripts of CfLRRop-2 were kept at a high level in oocytes and embryos, while those of CfLRRop-3 were expressed at a rather low level from oocytes to blastula. Their mRNA transcripts were significantly increased after the stimulation of lipopolysaccharide (LPS), peptidoglycan (PGN), glucan (GLU) and polyinosinic-polycytidylic acid (poly I:C), and the mRNA expression of CfLRRop-2 rose more intensely than that of CfLRRop-3. After the suppression of CfTLR (previously identified Toll-like receptor in C. farreri) via RNA interference (RNAi), CfLRRop-3 mRNA transcripts increased more intensely and lastingly than those of CfLRRop-2. The rCfLRRop-3 protein could bind LPS, PGN, GLU and poly I:C, while rCfLRRop-2 exhibited no significant binding activity to them. Additionally, rCfLRRop-2 could significantly induce the release of TNF-α from the mixed primary cultured scallop haemocytes, but rCfLRRop-3 failed. These results collectively indicated that CfLRRop-2 might act as an immune effector or pro-inflammatory factor, while CfLRRop-3 would function as a pattern recognition receptor (PRR), suggesting the function of LRR-only protein family has differentiated in scallop. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development and validation of an event-specific quantitative PCR method for genetically modified maize MIR162.

PubMed

Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

2014-01-01

A novel real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) maize event, MIR162. We first prepared a standard plasmid for MIR162 quantification. The conversion factor (Cf) required to calculate the genetically modified organism (GMO) amount was empirically determined for two real-time PCR instruments, the Applied Biosystems 7900HT (ABI7900) and the Applied Biosystems 7500 (ABI7500) for which the determined Cf values were 0.697 and 0.635, respectively. To validate the developed method, a blind test was carried out in an interlaboratory study. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr). The determined biases were less than 25% and the RSDr values were less than 20% at all evaluated concentrations. These results suggested that the limit of quantitation of the method was 0.5%, and that the developed method would thus be suitable for practical analyses for the detection and quantification of MIR162.

The duckweed Wolffia globosa as an indicator of heavy metal pollution: Sensitivity to Cr and Cd.

PubMed

Grag, P; Chandra, P

1994-01-01

The potential of Wolffia globosa, a profusely occurring rootless duckweed, was evaluated as an indicator of metal pollution in the water bodies. Plants of W. globosa were cultured in 3% Hoagland's nutrient medium which was supplemented with 0.05, 0.1, 1.0 and 2.0 mg/L of Cr and Cd. Plants showed substantial accumulation of both the metals at lowest concentrations. For example, at 0.05 ppm, the concentration factor (Cf) value for Cr was significantly higher (5616) than for Cd (1018). A high level of tolerance was shown by the plants to both Cr and Cd. The results show that the plants are sensitive to the variations in metal concentration and are capable of high metal enrichment at very low ambient concentration of the metals. This information may be useful for detecting metals in the water.

New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes

PubMed Central

Jiang, Chao; Krzyzanowski, Gary D.; Ryan, Wayne L.

2017-01-01

Cell-free DNA (cfDNA) in blood is used as a source of genetic material for noninvasive prenatal and cancer diagnostic assays in clinical practice. Recently we have started a project for new biomarker discovery with a view to developing new noninvasive diagnostic assays. While reviewing literature, it was found that exosomes may be a rich source of biomarkers, because exosomes play an important role in human health and disease. While characterizing exosomes found in human blood plasma, we observed the presence of cfDNA in plasma exosomes. Plasma was obtained from blood drawn into K3EDTA tubes. Exosomes were isolated from cell-free plasma using a commercially available kit. Sizing and enumeration of exosomes were done using electron microscopy and NanoSight particle counter. NanoSight and confocal microscopy was used to demonstrate the association between dsDNA and exosomes. DNA extracted from plasma and exosomes was measured by a fluorometric method and a droplet digital PCR (ddPCR) method. Size of extracellular vesicles isolated from plasma was heterogeneous and showed a mean value of 92.6 nm and a mode 39.7 nm. A large proportion of extracellular vesicles isolated from plasma were identified as exosomes using a fluorescence probe specific for exosomes and three protein markers, Hsp70, CD9 and CD63, that are commonly used to identify exosome fraction. Fluorescence dye that stain dsDNA showed the association between exosomes and dsDNA. Plasma cfDNA concentration analysis showed more than 93% of amplifiable cfDNA in plasma is located in plasma exosomes. Storage of a blood sample showed significant increases in exosome count and exosome DNA concentration. This study provide evidence that a large proportion of plasma cfDNA is localized in exosomes. Exosome release from cells is a metabolic energy dependent process, thus suggesting active release of cfDNA from cells as a source of cfDNA in plasma. PMID:28850588

New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes.

PubMed

Fernando, M Rohan; Jiang, Chao; Krzyzanowski, Gary D; Ryan, Wayne L

2017-01-01

Cell-free DNA (cfDNA) in blood is used as a source of genetic material for noninvasive prenatal and cancer diagnostic assays in clinical practice. Recently we have started a project for new biomarker discovery with a view to developing new noninvasive diagnostic assays. While reviewing literature, it was found that exosomes may be a rich source of biomarkers, because exosomes play an important role in human health and disease. While characterizing exosomes found in human blood plasma, we observed the presence of cfDNA in plasma exosomes. Plasma was obtained from blood drawn into K3EDTA tubes. Exosomes were isolated from cell-free plasma using a commercially available kit. Sizing and enumeration of exosomes were done using electron microscopy and NanoSight particle counter. NanoSight and confocal microscopy was used to demonstrate the association between dsDNA and exosomes. DNA extracted from plasma and exosomes was measured by a fluorometric method and a droplet digital PCR (ddPCR) method. Size of extracellular vesicles isolated from plasma was heterogeneous and showed a mean value of 92.6 nm and a mode 39.7 nm. A large proportion of extracellular vesicles isolated from plasma were identified as exosomes using a fluorescence probe specific for exosomes and three protein markers, Hsp70, CD9 and CD63, that are commonly used to identify exosome fraction. Fluorescence dye that stain dsDNA showed the association between exosomes and dsDNA. Plasma cfDNA concentration analysis showed more than 93% of amplifiable cfDNA in plasma is located in plasma exosomes. Storage of a blood sample showed significant increases in exosome count and exosome DNA concentration. This study provide evidence that a large proportion of plasma cfDNA is localized in exosomes. Exosome release from cells is a metabolic energy dependent process, thus suggesting active release of cfDNA from cells as a source of cfDNA in plasma.

High-intensity exercise of short duration alters bovine bone density and shape.

PubMed

Hiney, K M; Nielsen, B D; Rosenstein, D; Orth, M W; Marks, B P

2004-06-01

The ability of short-duration high-intensity exercise to stimulate bone formation in confinement was investigated using immature Holstein bull calves as a model. Eighteen bull calves, 8 wk of age, were assigned to one of three treatment groups: 1) group-housed (GR, which served as a control), 2) confined with no exercise (CF), or 3) confined with exercise (EX). The exercise protocol consisted of running 50 m on a concrete surface once daily, 5 d/wk. Confined calves remained stalled for the 42-d duration of the trial. Blood samples were taken to analyze concentrations of osteocalcin and deoxypyridinoline, markers of bone formation and resorption. At the completion of the trial, calves were humanely killed, and both forelegs were collected. The fused third and fourth metacarpal bone was scanned using computed tomography for determination of cross-sectional geometry and bone mineral density. Three-point bending tests to failure were performed on metacarpal bones. The exercise protocol resulted in the formation of a rounder bone in EX as well as in increased dorsal cortex thickness compared with those in the GR and CF. The exercised calves had a significantly smaller medullary cavity than CF and GR (P < 0.01) and a larger percentage of cortical bone area than CF (P < 0.01). Dorsal, palmar, and total bone mineral density was greater in EX than in CF (P < 0.05), and palmar and total bone mineral densities were greater (P < 0.05) in EX than in GR. There was a trend for the bones of EX to have a higher fracture force than CF (P < 0.10). Osteocalcin concentrations normalized from d 0 were higher in EX than CF (P < 0.05). Therefore, the exercise protocol altered bone shape and seemed to increase bone formation comparison with the stalled and group-housed calves.

Cocoa and cocoa fibre differentially modulate IgA and IgM production at mucosal sites.

PubMed

Massot-Cladera, Malen; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

2016-05-01

Previous studies have shown that a 10 % cocoa (C10) diet, containing polyphenols and fibre among others, modifies intestinal and systemic Ig production. The present study aimed at evaluating the impact of C10 on IgA and IgM production in the intestinal and extra-intestinal mucosal compartments, establishing the involvement of cocoa fibre (CF) in such effects. Mechanisms by which C10 intake may affect IgA synthesis in the salivary glands were also studied. To this effect, rats were fed either a standard diet, a diet containing C10, CF or inulin. Intestinal (the gut wash (GW), Peyer's patches (PP) and mesenteric lymph nodes (MLN)) and extra-intestinal (salivary glands) mucosal tissues and blood samples were collected for IgA and IgM quantification. The gene expressions of IgA production- and homing-related molecules were studied in the salivary glands. The C10 diet decreased intestinal IgA and IgM production. Although the CF diet decreased the GW IgA concentration, it increased PP, MLN and serum IgA concentrations. Both the C10 and the CF diets produced a down-regulatory effect on IgA secretion in the extra-intestinal tissues. The C10 diet interacted with the mechanisms involved in IgA synthesis, whereas the CF showed particular effects on the homing and transcytosis of IgA across the salivary glands. Overall, CF was able to up-regulate IgA production in the intestinal-inductor compartments, whereas it down-regulated its production at the mucosal-effector ones. Further studies must be directed to ascertain the mechanisms involved in the effect of particular cocoa components on gut-associated lymphoid tissue.

Topsoil and Deep Soil Organic Carbon Concentration and Stability Vary with Aggregate Size and Vegetation Type in Subtropical China

PubMed Central

Fang, Xiang-Min; Chen, Fu-Sheng; Wan, Song-Ze; Yang, Qing-Pei; Shi, Jian-Min

2015-01-01

The impact of reforestation on soil organic carbon (OC), especially in deep layer, is poorly understood and deep soil OC stabilization in relation with aggregation and vegetation type in afforested area is unknown. Here, we collected topsoil (0–15 cm) and deep soil (30–45 cm) from six paired coniferous forests (CF) and broad-leaved forests (BF) reforested in the early 1990s in subtropical China. Soil aggregates were separated by size by dry sieving and OC stability was measured by closed-jar alkali-absorption in 71 incubation days. Soil OC concentration and mean weight diameter were higher in BF than CF. The cumulative carbon mineralization (Cmin, mg CO2-C kg-1 soil) varied with aggregate size in BF and CF topsoils, and in deep soil, it was higher in larger aggregates than in smaller aggregates in BF, but not CF. The percentage of soil OC mineralized (SOCmin, % SOC) was in general higher in larger aggregates than in smaller aggregates. Meanwhile, SOCmin was greater in CF than in BF at topsoil and deep soil aggregates. In comparison to topsoil, deep soil aggregates generally exhibited a lower Cmin, and higher SOCmin. Total nitrogen (N) and the ratio of carbon to phosphorus (C/P) were generally higher in BF than in CF in topsoil and deep soil aggregates, while the same trend of N/P was only found in deep soil aggregates. Moreover, the SOCmin negatively correlated with OC, total N, C/P and N/P. This work suggests that reforested vegetation type might play an important role in soil OC storage through internal nutrient cycling. Soil depth and aggregate size influenced OC stability, and deep soil OC stability could be altered by vegetation reforested about 20 years. PMID:26418563

Calcium-dependent mitochondrial formation of species mediating DNA single strand breakage in U937 cells exposed to sublethal concentrations of tert-butylhydroperoxide.

PubMed

Guidarelli, A; Clementi, E; Sciorati, C; Cattabeni, F; Cantoni, O

1997-10-01

Treatment of U937 cells with a sublethal albeit DNA-damaging concentration of tert-butylhydroperoxide (tB-OOH) enhanced mitochondrial Ca++ uptake and ruthenium red (RR), a polycation that inhibits the calcium uniporter of mitochondria, significantly reduced the extent of DNA cleavage generated by the hydroperoxide. Release of Ca++ from the ryanodine(Ry)/caffeine(Cf)-sensitive stores further increased mitochondrial Ca++ uptake and elicited a parallel enhancement in DNA strand scission induced by tB-OOH that was prevented by both Ry and RR. DNA damage caused by tB-OOH alone or associated with either Cf or RR was prevented by iron chelators, insensitive to antioxidants and repaired with kinetics superimposable with those observed after treatment with H2O2. Cf enhanced the DNA-damaging effects of tB-OOH in permeabilized cells as well, and similar effects were observed upon addition of CaCl2. Cf did not further increase the formation of DNA lesions elicited by tB-OOH in the presence of CaCl2. The enhancing effects of Cf were prevented by RR and ryanodine, whereas those mediated by exogenous calcium were prevented only by RR. DNA strand scission caused by tB-OOH alone or associated with Cf in the permeabilized cell system was severely inhibited by ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid. The mechanism(s) whereby Ca++ promotes the mitochondrial formation of species that will ultimately result in the formation of DNA lesions was subsequently analyzed using intact as well as permeabilized cells. Hydrogen peroxide was identified to be one of these species.

Plasma cell-free DNA quantification is highly correlated to tumor burden in children with neuroblastoma.

PubMed

Wang, Xisi; Wang, Lijun; Su, Yan; Yue, Zhixia; Xing, Tianyu; Zhao, Wen; Zhao, Qian; Duan, Chao; Huang, Cheng; Zhang, Dawei; Jin, Mei; Cheng, Xianfeng; Chen, Shenglan; Liu, Yi; Ma, Xiaoli

2018-06-14

To evaluate plasma cell-free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy-nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow-up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE-1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE-1 300 bp fragment to the LINE-1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Prevalence of dyslipidemia in adults with cystic fibrosis.

PubMed

Rhodes, Bronwen; Nash, Edward F; Tullis, Elizabeth; Pencharz, Paul B; Brotherwood, Michelle; Dupuis, Annie; Stephenson, Anne

2010-01-01

A high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied. We conducted a retrospective review of adult CF patients attending St Michael's Hospital between January 2005 and December 2007. 334 patients (77% pancreatic insufficient (PI)) were included in the study. Mean HDL cholesterol was significantly lower in males (p<0.0001) with 44% of males having HDL cholesterol <38.7mg/dL(1mmol/L). Pancreatic sufficient patients were more likely than PI subjects to have total cholesterol >201mg/dL(5.2mmol/L) (p<0.01). 5% of subjects had triglyceride concentrations >195mg/dL(2.2mmol/L). Diabetes was diagnosed in 23% of subjects. Lipid profiles were similar between diabetics and non-diabetics. Total cholesterol and triglycerides both increased with increasing age and increasing BMI (p<0.01). Dyslipidemia occurs in CF patients however no differences in lipid profiles were seen between those with diabetes and those without. Fasting lipids should be monitored in CF patients, particularly those with PS, older age, and high BMI. As survival in CF increases, the prevalence of dyslipidemia may increase resulting in clinically important complications.

Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

PubMed

Sprauten, M; Haugnes, H S; Brydøy, M; Kiserud, C; Tandstad, T; Bjøro, T; Bjerner, J; Cvancarova, M; Fosså, S D; Oldenburg, J

2015-10-01

Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Relative Contribution of Genetic and Non-genetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

PubMed Central

Blackman, Scott M.; Deering-Brose, Rebecca; McWilliams, Rita; Naughton, Kathleen; Coleman, Barbara; Lai, Teresa; Algire, Marilyn; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Fallin, M. Daniele; West, Kristen; Arking, Dan E.; Chakravarti, Aravinda; Cutler, David J.; Cutting, Garry R

2006-01-01

Background & Aims Neonatal intestinal obstruction (meconium ileus or MI) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and non-genetic modifiers to the development of this major complication of CF. Methods Using clinical data and DNA collected by the CF Twin and Sibling Study, 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage. Results Specific mutations in CFTR, the gene responsible for CF, correlated with MI indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (p=1×10−5) demonstrating that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (DIOS; p=8×10−4). Unlike MI, concordance analysis indicated that the risk for development of DIOS in CF patients is primarily due to non-genetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene within the CFM1 region on chromosome 19 that had previously been linked to MI. Conclusions The CFTR gene along with two or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, while intestinal obstruction in older CF patients is primarily due to non-genetic factors. PMID:17030173

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

PubMed Central

Stefano, Daniela De; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; Gregorio, Fabiola De; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; Rosa, Giuseppe De; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in CftrF508del homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation. PMID:25350163

8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine concentrations in various human body fluids: implications for their measurement and interpretation.

PubMed

Hu, Chiung-Wen; Cooke, Marcus S; Tsai, Yi-Hung; Chao, Mu-Rong

2015-02-01

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium hydroxide-methanol were, respectively, selected for plasma and saliva samples due to their effect on recovery efficiencies and chromatography. The mean baseline concentrations of 8-oxoGua and 8-oxodGuo in plasma were demonstrated to be 0.21 and 0.016 ng/mL, respectively, while in saliva they were 0.85 and 0.010 ng/mL, respectively. A relatively high concentration of 8-oxoGua was found in saliva with a concentration factor (CF, concentration ratio of saliva to plasma) of 4 as compared to that of 8-oxodGuo (CF: 0.6), implying that 8-oxoGua in plasma may be actively transported to saliva, whereas 8-oxodGuo was most dependent on a passive diffusion. Good correlations between urine and plasma concentrations were observed for 8-oxoGua and 8-oxodGuo, suggesting that blood was a suitable matrix in addition to urine. Significant correlation between 8-oxoGua and 8-oxodGuo in urine was only observed when the concentrations were not corrected for urinary creatinine, raising the issue of applicability of urinary creatinine to adjust 8-oxoGua concentrations.

Influence of ciprofloxacin-based additives on the hydrolysis of nanofiber polyurethane membranes.

PubMed

Wright, Meghan E E; Wong, Andrew T; Levitt, Daniel; Parrag, Ian C; Yang, Meilin; Santerre, J Paul

2018-05-01

A degradable polycarbonate urethane (PCNU) and an antimicrobial oligomer (AO) were used to generate anti-infective nanofiber scaffolds through blend electrospinning. The AO consists of two molecules of ciprofloxacin (CF) bound through hydrolysable linkages to triethylene glycol. The membranes were conceived for use as tissue engineering scaffolds for the regeneration of soft tissues for the periodontium, where there would be a need for a local dose of antibiotic to the periodontal space as the scaffold degrades in order to prevent biomaterial-associated infection. Scaffolds were made using AO at 7 and 15% w/w equivalent CF, and compared to scaffolds with 15% w/w CF (with HCl counterion). AO was hydrolyzed and released CF continuously over 28 days, while the 15% w/w CF HCl scaffolds showed a burst release within hours, with no subsequent release in the subsequent 28 day period. Released CF from both the AO and CF HCl scaffolds had a similar minimum inhibitory concentration to that of off-the-shelf CF. Interestingly, the introduction of drug in either form (AO or CF HCl) was found to increase the hydrolytic stability of the electrospun degradable PCNU scaffold matrix itself. The alteration of hydrolysis kinetics was attributed to changes in the hydrogen bonding character and microstructure within the scaffolds, introduced by the presence of CF. This study has revealed that in generating in situ drug release systems, the secondary effects of the added drug on the degradation properties of the polymeric carriers must be considered, particularly for systems that act dually as tissue engineering scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1211-1222, 2018. © 2018 Wiley Periodicals, Inc.

Dating groundwater with trifluoromethyl sulfurpentafluoride (SF 5CF3), sulfur hexafluoride (SF6), CF 3Cl (CFC-13), and CF2Cl2 (CFC-12)

USGS Publications Warehouse

Busenberg, E.; Plummer, Niel

2008-01-01

[1] A new groundwater dating procedure using the transient atmospheric signal of the environmental tracers SF5CF3, CFC-13, SF6, and CFC-12 was developed. The analytical procedure determines concentrations of the four tracers in air and water samples. SF 5CF3 and CFC-13 can be used to date groundwaters in some environments where the CFCs and SF6 have previously failed because these new tracers have increasing atmospheric input functions, no known terrigenic source, and are believed to be stable under reducing conditions. SF5CF3 has a dating range from 1970 to modern; the mixing ratio (mole fraction) in North American air has increased from the detection limit of 0.005 parts per trillion (ppt) to the 2006 mole fraction of about 0.16 ppt. No evidence was found for degradation of SF5CF3 in laboratory anaerobic systems. The solubility of SF5CF3 was measured in water from 1 to 35??C. Groundwater samples that contained large amounts of terrigenic SF6 did not contain terrigenic SF 5CF3. CFC-13 is a trace atmospheric gas with a dating range in groundwater of about 1965 to modem. CFC-13 has been used primarily in very low-temperature refrigeration; thus groundwater environments are less likely to be contaminated with nonatmospheric sources as compared to other widely used CFCs. Because of the low solubility of SF5CF3 and CFC-13 in water, an excess air correction must be applied to the apparent ages. The new dating procedure was tested in water samples from wells and springs from Maryland, Virginia, and West Virginia.

Analytical validation of BRAF mutation testing from circulating free DNA using the amplification refractory mutation testing system.

PubMed

Aung, Kyaw L; Donald, Emma; Ellison, Gillian; Bujac, Sarah; Fletcher, Lynn; Cantarini, Mireille; Brady, Ged; Orr, Maria; Clack, Glen; Ranson, Malcolm; Dive, Caroline; Hughes, Andrew

2014-05-01

BRAF mutation testing from circulating free DNA (cfDNA) using the amplification refractory mutation testing system (ARMS) holds potential as a surrogate for tumor mutation testing. Robust assay validation is needed to establish the optimal clinical matrix for measurement and cfDNA-specific mutation calling criteria. Plasma- and serum-derived cfDNA samples from 221 advanced melanoma patients were analyzed for BRAF c.1799T>A (p.V600E) mutation using ARMS in two stages in a blinded fashion. cfDNA-specific mutation calling criteria were defined in stage 1 and validated in stage 2. cfDNA concentrations in serum and plasma, and the sensitivities and specificities of BRAF mutation detection in these two clinical matrices were compared. Sensitivity of BRAF c.1799T>A (p.V600E) mutation detection in cfDNA was increased by using mutation calling criteria optimized for cfDNA (these criteria were adjusted from those used for archival tumor biopsies) without compromising specificity. Sensitivity of BRAF mutation detection in serum was 44% (95% CI, 35% to 53%) and in plasma 52% (95% CI, 43% to 61%). Specificity was 96% (95% CI, 90% to 99%) in both matrices. Serum contains significantly higher total cfDNA than plasma, whereas the proportion of tumor-derived mutant DNA was significantly higher in plasma. Using mutation calling criteria optimized for cfDNA improves sensitivity of BRAF c.1799T>A (p.V600E) mutation detection. The proportion of tumor-derived cfDNA in plasma was significantly higher than in serum. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: Ba V, Ba VI, and Ba VII oscillator strengths (Rauch+, 2014)

NASA Astrophysics Data System (ADS)

Rauch, T.; Werner, K.; Quinet, P.; Kruk, J. W.

2014-04-01

table1.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba V. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. table2.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba VI. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. table3.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba VII. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. (3 data files).

Effects of Combined Application of Biogas Slurry and Chemical Fertilizer on Soil Aggregation and C/N Distribution in an Ultisol.

PubMed

Zheng, Xuebo; Fan, Jianbo; Xu, Lei; Zhou, Jing

2017-01-01

Unreasonable use of chemical fertilizer (CF) on agricultural soil leads to massive losses of soil organic carbon (SOC) and total nitrogen (TN) in tropical and subtropical areas, where soil conditions are unfavorable for aggregate formation. This study evaluated the effects of combined application of biogas slurry (BS) plus CF on soil aggregation and aggregate-associated C/N concentration and storage in an Ultisol. Six treatments included: no fertilizer (T1), CF only (T2), partial (15% (T3), 30% (T4) and 45% (T5)) substitution of TN with BS and BS only (T6). Soil mechanical-stable aggregates (MSAs) formation and stability as well as MSAs-associated C/N concentration and storage were observed in different aggregate sizes (>5, 5-2, 2-1, 1.0-0.5, 0.50-0.25 and <0.25 mm). The proportion of MSAs >5 mm significantly increased with BS substitution (T5), while the proportions of MSAs 1.0-0.5 mm, MSAs 0.50-0.25 mm and MSAs <0.25 mm significantly decreased. Both mean weight diameter and geometric mean diameter were highest in T5, which improved soil aggregation stability as well as resulted in significantly higher SOC and TN concentrations and storage in MSAs >0.5 mm that constituted 72-82% of MSAs. Stepwise regression analysis showed that MSAs >5 mm, SOC in MSAs >5 mm and TN in MSAs >5 mm were the dominant variables affecting aggregate stability. Meanwhile SOC in MSAs <0.25 mm and TN in MSAs 2-1 mm were independent variables affecting SOC and TN concentrations in bulk soils. Therefore, certain rate of combined application of BS plus CF is an effective, eco-friendly way to improve soil quality in an Ultisol.

Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms.

PubMed

Kennedy, Sarah; Beaudoin, Trevor; Yau, Yvonne C W; Caraher, Emma; Zlosnik, James E A; Speert, David P; LiPuma, John J; Tullis, Elizabeth; Waters, Valerie

2016-01-01

Pulmonary infection with Burkholderia cepacia complex in cystic fibrosis (CF) patients is associated with more-rapid lung function decline and earlier death than in CF patients without this infection. In this study, we used confocal microscopy to visualize the effects of various concentrations of tobramycin, achievable with systemic and aerosolized drug administration, on mature B. cepacia complex biofilms, both in the presence and absence of CF sputum. After 24 h of growth, biofilm thickness was significantly reduced by exposure to 2,000 μg/ml of tobramycin for Burkholderia cepacia, Burkholderia multivorans, and Burkholderia vietnamiensis; 200 μg/ml of tobramycin was sufficient to reduce the thickness of Burkholderia dolosa biofilm. With a more mature 48-h biofilm, significant reductions in thickness were seen with tobramycin at concentrations of ≥100 μg/ml for all Burkholderia species. In addition, an increased ratio of dead to live cells was observed in comparison to control with tobramycin concentrations of ≥200 μg/ml for B. cepacia and B. dolosa (24 h) and ≥100 μg/ml for Burkholderia cenocepacia and B. dolosa (48 h). Although sputum significantly increased biofilm thickness, tobramycin concentrations of 1,000 μg/ml were still able to significantly reduce biofilm thickness of all B. cepacia complex species with the exception of B. vietnamiensis. In the presence of sputum, 1,000 μg/ml of tobramycin significantly increased the dead-to-live ratio only for B. multivorans compared to control. In summary, although killing is attenuated, high-dose tobramycin can effectively decrease the thickness of B. cepacia complex biofilms, even in the presence of sputum, suggesting a possible role as a suppressive therapy in CF. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

PubMed

Ciuca, Ioana M; Pop, Liviu L; Rogobete, Alexandru F; Onet, Dan I; Guta-Almajan, Bogdan; Popa, Zoran; Horhat, Florin G

2016-09-01

Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

A cross-sectional pilot study of compassion fatigue, burnout, and compassion satisfaction in pediatric palliative care providers in the United States.

PubMed

Kase, Samuel M; Waldman, Elisha D; Weintraub, Andrea S

2018-02-05

Compassion fatigue (CF) is secondary traumatic distress experienced by providers from contact with patients' suffering. Burnout (BO) is job-related distress resulting from uncontrollable workplace factors that manifest in career dissatisfaction. Compassion satisfaction (CS) is emotional fulfillment derived from caring for others. The literature on BO in healthcare providers is extensive, whereas CF and CS have not been comprehensively studied. Because of ongoing exposure to patient and family distress, pediatric palliative care (PPC) providers may be at particular risk for CF. We conducted a cross-sectional pilot study of CF, BO, and CS among PPC providers across the United States. The Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of professional and personal characteristics were distributed electronically and anonymously to PPC physicians and nurses. Logistic and linear regression models for CF, BO, and CS as a function of potential risk factors were constructed. The survey response rate was 39%, primarily consisting of female, Caucasian providers. The prevalence of CF, BO, and CS was 18%, 12%, and 25%, respectively. Distress about a "clinical situation," physical exhaustion, and personal loss were identified as significant determinants of CF. Distress about "coworkers," emotional depletion, social isolation, and "recent involvement in a clinical situation in which life-prolonging activities were not introduced" were significant determinants of BO. Physical exhaustion, personal history of trauma, "recent involvement in a clinical situation in which life-prolonging activities were not introduced," and not discussing distressing issues were significant predictors of lower CS scores. Significance of results CF and BO directly influence the well-being and professional performance of PPC providers. To provide effective compassionate care to patients, PPC providers must be attentive to predictors of these phenomena. Further work is needed to explore additional causes of CF, BO, and CS in PPC providers as well as potential interventions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khanal, Suraj P.; Mahfuz, Hassan; Rondinone, Adam Justin

The potential of improving the fracture toughness of synthetic hydroxyapatite (HAp) by incorporating carboxyl functionalized single walled carbon nanotubes (CfSWCNTs) and polymerized ε-caprolactam (nylon) was researched. A series of HAp samples with CfSWCNTs concentrations varying from 0 to 1.5 wt.%, without, and with nylon addition was prepared. X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM) were used to characterize the samples. The three point bending test was applied to measure the fracture toughness of the composites. A reproducible value of 3.6 ± 0.3 MPa.√m was found for samples containing 1 wt.% CfSWCNTs and nylon. This valuemore » is in the range of the cortical bone fracture toughness. Lastly, the increase of the CfSWCNTs content results to decrease of the fracture toughness, and formation of secondary phases.« less

Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

PubMed Central

Khan, Babar K.; Raz, Assaf; Rotolo, Jimmy A.; Wittekind, Michael

2017-01-01

ABSTRACT Biofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to target Staphylococcus aureus biofilms. We used minimum biofilm-eradicating concentration (MBEC) assays on 95 S. aureus strains to obtain a 90% MBEC (MBEC90) value of ≤0.25 μg/ml for CF-301. Mature biofilms of coagulase-negative staphylococci, Streptococcus pyogenes, and Streptococcus agalactiae were also sensitive to disruption, with MBEC90 values ranging from 0.25 to 8 μg/ml. The potency of CF-301 was demonstrated against S. aureus biofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed by S. aureus and Staphylococcus epidermidis on several surfaces, were removed by CF-301, as were S. aureus biofilms either enriched for small-colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated against S. aureus persister cells in exponential-phase and stationary-phase populations. Finally, the antibiofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range of S. aureus strains. In all, the data show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component. PMID:28461319

Skin Biomarkers for Cystic Fibrosis: A Potential Non-Invasive Approach for Patient Screening.

PubMed

Esteves, Cibele Zanardi; de Aguiar Dias, Letícia; de Oliveira Lima, Estela; de Oliveira, Diogo Noin; Rodrigues Melo, Carlos Fernando Odir; Delafiori, Jeany; Souza Gomez, Carla Cristina; Ribeiro, José Dirceu; Ribeiro, Antônio Fernando; Levy, Carlos Emílio; Catharino, Rodrigo Ramos

2017-01-01

Cystic fibrosis (CF) is a disabling genetic disease with an increased prevalence in European heritage populations. Currently, the most used technique for collection of CF samples and diagnosis is provided through uncomfortable tests, with uncertain results, mostly based on chloride concentration in sweat. Since CF mutation induces many metabolic changes in patients, exploring these alterations might be an alternative to visualize potential biomarkers that could be used as interesting tools for further diagnostic upgrade, prioritizing simplicity, low cost, and quickness. This contribution describes an accurate strategy to provide potential biomarkers related to CF, which may be understood as a potential tool for new diagnostic approaches and/or for monitoring disease evolution. Therefore, the present proposal consists of using skin imprints on silica plates as a way of sample collection, followed by direct-infusion high-resolution mass spectrometry and multivariate data analysis, intending to identify metabolic changes in skin composition of CF patients. Metabolomics analysis allowed identifying chemical markers that can be traced back to CF in patients' skin imprints, differently from control subjects. Seven chemical markers from several molecular classes were elected, represented by bile acids, a glutaric acid derivative, thyrotropin-releasing hormone, an inflammatory mediator, a phosphatidic acid, and diacylglycerol isomers, all reflecting metabolic disturbances that occur due to of CF. The comfortable method of sample collection combined with the identified set of biomarkers represent potential tools that open the range of possibilities to manage CF and follow the disease evolution. This exploratory approach points to new perspectives about the development of diagnostic assay using biomarkers and the management CF.

Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities

PubMed Central

Vázquez-Del Mercado, Mónica; Gomez-Bañuelos, Eduardo; Chavarria-Avila, Efrain; Cardona-Muñoz, Ernesto; Ramos-Becerra, Carlos; Alanis-Sanchez, Adrián; Cardona-Muller, David; Grover-Paez, Fernando; Perez-Vazquez, Felipe de J.; Navarro-Hernandez, Rosa-Elena; Valadez-Soto, Jorge M.; Saldaña-Millan, Adan A.; Gonzalez-Rosas, Lorena; Ramos-Lopez, Gabriel; Petri, Marcelo H.; Bäck, Magnus

2017-01-01

Abstract The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities. Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ± 1.8 vs 7.0 ± 0.8) and ≥2 to <10 years (8.4 ± 1.8 vs 7.8 ± 1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the β-coefficients, each year of disease duration (β = 0.072) had a greater impact on cfPWV than age (β = 0.054). Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years. PMID:28816989

Long-term combined chemical and manure fertilizations increase soil organic carbon and total nitrogen in aggregate fractions at three typical cropland soils in China.

PubMed

He, Y T; Zhang, W J; Xu, M G; Tong, X G; Sun, F X; Wang, J Z; Huang, S M; Zhu, P; He, X H

2015-11-01

Soil organic carbon (SOC), total nitrogen (TN), microbial biomass carbon (MBC) and nitrogen (MBN) are important factors of soil fertility. However, effects of the combined chemical fertilizer and organic manure or straw on these factors and their relationships are less addressed under long-term fertilizations. This study addressed changes in SOC, TN, MBC and MBN at 0-20 cm soil depth under three 17 years (September 1990-September 2007) long-term fertilization croplands along a heat and water gradient in China. Four soil physical fractions (coarse free and fine free particulate organic C, cfPOC and ffPOC; intra-microaggregate POC, iPOC; and mineral associated organic C, MOC) were examined under five fertilizations: unfertilized control, chemical nitrogen (N), phosphorus (P) and potassium (K) (NPK), NPK plus straw (NPKS, hereafter straw return), and NPK plus manure (NPKM and 1.5NPKM, hereafter manure). Compared with Control, manure significantly increased all tested parameters. SOC and TN in fractions distributed as MOC > iPOC > cfPOC > ffPOC with the highest increase in cfPOC (329.3%) and cfPTN (431.1%), and the lowest in MOC (40.8%) and MTN (45.4%) under manure. SOC significantly positively correlated with MBC, cfPOC, ffPOC, iPOC and MOC (R(2) = 0.51-0.84, P < 0.01), while TN with cfPTN, ffPTN, iPTN and MTN (R(2) = 0.45-0.79, P < 0.01), but not with MBN, respectively. Principal component analyses explained 86.9-91.2% variance of SOC, TN, MBC, MBN, SOC and TN in each fraction. Our results demonstrated that cfPOC was a sensitive SOC indicator and manure addition was the best fertilization for improving soil fertility while straw return should take into account climate factors in Chinese croplands. Copyright © 2015 Elsevier B.V. All rights reserved.

A statistical model to predict one-year risk of death in patients with cystic fibrosis.

PubMed

Aaron, Shawn D; Stephenson, Anne L; Cameron, Donald W; Whitmore, George A

2015-11-01

We constructed a statistical model to assess the risk of death for cystic fibrosis (CF) patients between scheduled annual clinical visits. Our model includes a CF health index that shows the influence of risk factors on CF chronic health and on the severity and frequency of CF exacerbations. Our study used Canadian CF registry data for 3,794 CF patients born after 1970. Data up to 2010 were analyzed, yielding 44,390 annual visit records. Our stochastic process model postulates that CF health between annual clinical visits is a superposition of chronic disease progression and an exacerbation shock stream. Death occurs when an exacerbation carries CF health across a critical threshold. The data constitute censored survival data, and hence, threshold regression was used to connect CF death to study covariates. Maximum likelihood estimates were used to determine which clinical covariates were included within the regression functions for both CF chronic health and CF exacerbations. Lung function, Pseudomonas aeruginosa infection, CF-related diabetes, weight deficiency, pancreatic insufficiency, and the deltaF508 homozygous mutation were significantly associated with CF chronic health status. Lung function, age, gender, age at CF diagnosis, P aeruginosa infection, body mass index <18.5, number of previous hospitalizations for CF exacerbations in the preceding year, and decline in forced expiratory volume in 1 second in the preceding year were significantly associated with CF exacerbations. When combined in one summative model, the regression functions for CF chronic health and CF exacerbation risk provided a simple clinical scoring tool for assessing 1-year risk of death for an individual CF patient. Goodness-of-fit tests of the model showed very encouraging results. We confirmed predictive validity of the model by comparing actual and estimated deaths in repeated hold-out samples from the data set and showed excellent agreement between estimated and actual mortality. Our threshold regression model incorporates a composite CF chronic health status index and an exacerbation risk index to produce an accurate clinical scoring tool for prediction of 1-year survival of CF patients. Our tool can be used by clinicians to decide on optimal timing for lung transplant referral. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronobiological factors for compassion satisfaction and fatigue among ambulatory oncology caregivers.

PubMed

Bellicoso, Daniela; Trudeau, Maureen; Fitch, Margaret I; Ralph, Martin R

2017-01-01

Primary caregivers for victims of chronic illness and or trauma experience both positive and negative emotional consequences. These are broadly classified as compassion satisfaction (CS) and compassion fatigue (CF). Because one of the components of CF, burnout, varies with chronotype and sleep quality, we assessed the influence of chronobiological features on the broader constructs of CS and CF. Responses from primary ambulatory care oncology staff working dayshifts were assessed for potential relationships of chronotype and sleep quality with CS and CF using the professional quality of life scale. These were analyzed further in a multivariate model that included personality and job satisfaction as cofactors. We found that sleep quality was a key contributor to CS development and CF reduction. Morningness was positively linked to CS, but the univariate association was masked in the multivariate model. Job satisfaction (contingent rewards, nature of work and operating procedures) heavily influenced CS and CF development. Agreeableness and openness showed positive correlations with CS and negative with burnout, while emotional stability was linked to reduced CF. While job satisfaction and personality predictably played roles in the development of CS and CF, sleep quality and chronotype contributed significantly to benefits and negative consequences of providing care.

Multilayer regulatory mechanisms control cleavage factor I proteins in filamentous fungi

PubMed Central

Rodríguez-Romero, J.; Franceschetti, M.; Bueno, E.; Sesma, A.

2015-01-01

Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs. PMID:25514925

Risk factors for onset of persistent respiratory symptoms in children with cystic fibrosis.

PubMed

McColley, Susanna A; Ren, Clement L; Schechter, Michael S; Regelmann, Warren E; Pasta, David J; Konstan, Michael W

2012-10-01

To characterize the onset of persistent signs and symptoms of cystic fibrosis (CF) lung disease and identify characteristics that predict onset. Patients in the Epidemiologic Study of CF who were <4 years of age at enrollment and had ≥2 years of follow-up were included. We defined persistence as a sign or symptom that was present during two consecutive encounters separated by 60-365 days, and persistent clubbing as ≥50% of encounters with clubbing within 365 days. Predictors were assessed in a Cox proportional hazards model for age at first occurrence of each symptom. Each sign or symptom met the criterion of persistence in a substantial proportion of patients during a follow-up period of 7 ± 3 years (mean ± SD; range 2-12). Risk factors that predicted earlier onset of signs and symptoms included pancreatic enzyme use, Pseudomonas aeruginosa infection, and prior diagnosis of asthma. Other risk factors had variable effects on signs and symptoms. Signs and symptoms of lung disease begin early in CF. Risk factors previously reported for lower forced expiratory volume in 1 sec are also associated with earlier onset of persistent signs and symptoms of CF lung disease, but their impact varies. Copyright © 2012 Wiley Periodicals, Inc.

Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis.

PubMed

Roum, J H; Borok, Z; McElvaney, N G; Grimes, G J; Bokser, A D; Buhl, R; Crystal, R G

1999-07-01

Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified, since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to seven patients with CF. ELF total, reduced, and oxidized GSH increased (P < 0.05, all compared with before GSH therapy), suggesting adequate RES delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated superoxide anion (O2-.) release by ELF inflammatory cells decreased after GSH therapy (P < 0.002). This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed O2-. release (P < 0.001). No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF and support the rationale for further clinical evaluation.

South African adolescents with cystic fibrosis: a qualitative exploration of their bio-psychosocial fields.

PubMed

Hugo, Carina Jacobie; van der Merwe, Mariette

2014-01-01

This qualitative case study explored risk factors and protective factors in the bio-psychosocial fields of adolescents living with cystic fibrosis (CF). Semi-structured interviews were conducted with adolescents in the middle and late adolescent years (15-22 years) who had the defining characteristics of CF and were living in Gauteng province. Themes emerged from individual interviews. The fundamental human need to be understood and to understand was negatively affected as the illness affected socialisation and learning. Participants experienced an array of emotions including loss and bereavement linked to their illness and when friends with CF died. Constructive internal dialogue and positive thinking emerged as protective variables. Participants generally showed awareness of how they regulated their contact with the illness and how they self-regulate. Despite the severity of their symptoms and the taxing demands of managing CF, participants expressed hope for the future and could find some meaning in the illness. Adolescents with CF who participated in this study indicated that they felt different from their peers. Apart from the general developmental tasks typical to adolescence they faced the challenge of managing a severe chronic and potentially terminal illness.

A Preliminary Analysis of Compassion Satisfaction and Compassion Fatigue With Considerations for Nursing Unit Specialization and Demographic Factors.

PubMed

Mooney, Claire; Fetter, Katrina; Gross, Brian W; Rinehart, Cole; Lynch, Caitlin; Rogers, Frederick B

Compassion fatigue (CF), or vicarious traumatization, is a state of physical/emotional distress that results from caring for those experiencing pain. We sought to characterize levels of CF in intensive care unit (ICU) and oncology nursing populations with subanalyses comparing specific personal/professional demographic factors. The Professional Quality of Life (ProQOL) scale, a validated tool for assessing CF, burnout (BO), and compassion satisfaction (CS), was distributed to the ICU and oncology divisions of a community hospital. Demographic data and ProQOL scale scores were collected and compared within specialty and gender subgroups. Two-sample t tests and regression analyses were used to compare groups. Statistical significance was defined as p < .05. A total of 86 nurses submitted completed surveys able to be analyzed. Levels of CS were significantly lower (p = .023) and levels of BO were significantly higher (p = .029) in ICU nurses than in oncology nurses. Male nurses exhibited significantly higher CS (p = .001) and significantly lower BO (p = .021) and CF (p = .014) than female nurses. Intensive care unit nurses and female nurses from both ICU and oncology specialties may be at increased risk for developing a poorer overall ProQOL and CF.

Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications.

PubMed

Cohen-Cymberknoh, Malena; Kerem, Eitan; Ferkol, Thomas; Elizur, Arnon

2013-12-01

Airway epithelial cells and immune cells participate in the inflammatory process responsible for much of the pathology found in the lung of patients with cystic fibrosis (CF). Intense bronchial neutrophilic inflammation and release of proteases and oxygen radicals perpetuate the vicious cycle and progressively damage the airways. In vitro studies suggest that CF transmembrane conductance regulator (CFTR)-deficient airway epithelial cells display signalling abnormalities and aberrant intracellular processes which lead to transcription of inflammatory mediators. Several transcription factors, especially nuclear factor-κB, are activated. In addition, the accumulation of abnormally processed CFTR in the endoplasmic reticulum results in unfolded protein responses that trigger 'cell stress' and apoptosis leading to dysregulation of the epithelial cells and innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation. Measuring airway inflammation is crucial for initiating treatment and monitoring its effect. No inflammatory biomarker predictive for the clinical course of CF lung disease is currently known, although neutrophil elastase seems to correlate with lung function decline. CF animal models mimicking human lung disease may provide an important insight into the pathogenesis of lung inflammation in CF and identify new therapeutic targets.

HIV Infection Is Not Associated With Aortic Stiffness. Traditional Cardiovascular Risk Factors Are the Main Determinants-Cross-sectional Results of INI-ELSA-BRASIL.

PubMed

Moreira, Rodrigo C; Mill, José G; Grinsztejn, Beatriz; Veloso, Valdilea; Fonseca, Maria de Jesus; Griep, Rosane H; Bensenor, Isabela; Cardoso, Sandra W; Lotufo, Paulo; Chor, Dora; Pacheco, Antonio G

2018-05-01

Aortic stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) is a marker of subclinical atherosclerosis. We propose to assess whether HIV infection is associated with arterial stiffness and their determinants in HIV-infected subjects. We compared data from an HIV cohort (644 patients, HIV+) in Rio de Janeiro with 2 groups: 105 HIV-negative (HIV-) individuals and 14,873 participants of the ELSA-Brasil study. We used multivariable linear regression to investigate factors associated with cf-PWV and whether HIV was independently associated with aortic stiffness and propensity score weighting to control for imbalances between groups. From 15,860 participants, cf-PWV was obtained in 15,622 (98.5%). Median age was 51 (interquartile range 45-58), 44.41 (35.73, 54.72), and 43.60 (36.01, 50.79) years (P < 0.001), and median cf-PWV (m/s; interquartile range) was 9.0 (8.10, 10.20), 8.70 (7.90, 10.20), and 8.48 (7.66, 9.40) for ELSA-Brasil, HIV- and HIV+, respectively (P < 0.001). In the final weighted multivariable models, HIV group was not associated with cf-PWV when compared either with ELSA-Brasil [β = -0.05; 95% confidence interval (CI) = -0.23; P = 0.12; P = 0.52] or with the HIV- groups (β = 0.10; 95% CI = -0.10; 0, 31; P = 0.32). Traditional risk factors were associated with higher cf-PWV levels in the HIV+ group, particularly waist-to-hip ratio (β = 0.20; 95% CI = 0.10; 0.30; P < 0.001, result per one SD change). HIV infection was not associated with higher aortic stiffness according to our study. In HIV-infected subjects, the stiffness of large arteries is mainly associated with traditional risk factors and not to the HIV infection per se.

Respiratory physicians and clinic coordinators' attitudes to population-based cystic fibrosis carrier screening.

PubMed

Cunningham, Fiona; Lewis, Sharon; Curnow, Lisette; Glazner, Judith; Massie, John

2014-01-01

Attitudes of Australian CF healthcare professionals toward population-based cystic fibrosis (CF) carrier screening were examined. A purpose-designed questionnaire was distributed to 111 respiratory physicians and 30 CF clinic coordinators throughout Australia. Seventy-one questionnaires (52 physicians and 19 coordinators (46.8%, 63.3% respectively)) were returned. Forty respondents (56.3%) supported population-based carrier screening for CF. Support for screening was associated with rating the factors: carrier risk being 1 in 25 (OR 1.72 (1.12, 2.65)), reassurance when both partners test negative (OR 1.67 (1.12, 2.46)) and the daily treatment regimen for CF patients (OR 1.59 (1.05, 2.42)) as important. Opposition to screening was associated with identifying potential discrimination against carriers as a disadvantage (OR 0.3 (0.12, 0.88)), and limitations of predicting clinical outcomes as a barrier (OR 0.46 (0.25, 0.83)). There is moderate support for population-based carrier screening for CF by Australian CF healthcare professionals. Perceived barriers to implementation are surmountable. © 2013.

Correlates of Segmental Pulse Wave Velocity in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Meyer, Michelle L; Tanaka, Hirofumi; Palta, Priya; Cheng, Susan; Gouskova, Natalia; Aguilar, David; Heiss, Gerardo

2016-01-01

Carotid-femoral PWV (cfPWV) is a well-established measure of central arterial stiffness, while brachial-ankle PWV (baPWV) is being used more frequently in East Asian countries. Few studies have simultaneously characterized the distributions and correlates of segment-specific PWV measures and their associations with cardiovascular risk factors. We evaluated segment-specific PWV (cfPWV, baPWV, and femoral-ankle (faPWV)) in 4,974 older-aged African American and Caucasian adults in the community-based Atherosclerosis Risk in Communities (ARIC) Study using a standardized protocol and the OMRON VP-1000 Plus system. We examined the distribution and multivariable-adjusted correlates of PWV measures by race and sex. Mean age ranged from 74 ± 5 to 76 ± 5 years across race-sex groups. In all race-sex groups, cfPWV correlated with baPWV but not with faPWV, and cfPWV and baPWV were higher with age, whereas faPWV was not. Heart rate and systolic blood pressure (SBP) were positively associated and weight was negatively associated with all PWV measures; however, the associations with age, glycated hemoglobin, triglycerides, and high-density lipoprotein (HDL) cholesterol varied by segment and race-sex group. Our findings indicate that cfPWV and faPWV reflect distinct aspects of segment-specific vascular stiffness and their associated profile of cardiovascular risk factors. Even among older adults, age is associated with higher cfPWV and baPWV, but not with faPWV. Understanding factors that ostensibly play a role in increasing arterial stiffness in different arterial territories can inform opportunities for cardiovascular disease (CVD) prevention and risk management. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Potentially toxic elements in soil of the Khyber Pakhtunkhwa province and Tribal areas, Pakistan: evaluation for human and ecological risk assessment.

PubMed

Saddique, Umar; Muhammad, Said; Tariq, Mohsin; Zhang, Hua; Arif, Mohammad; Jadoon, Ishtiaq A K; Khattak, Nimat Ullah

2018-03-22

Potentially toxic elements (PTEs) contaminations in the soil ecosystem are considered as extremely hazardous due to toxicity, persistence and bioaccumulative nature. Therefore, this study was aimed to summarize the results of published PTEs in soil of Khyber Pakhtunkhwa and Tribal areas, Pakistan. Results were evaluated for the pollution quantification factors, including contamination factor (CF), pollution load index (PLI), ecological risk index (ERI) and human health risk assessment. The highest CF (797) and PLI (7.35) values were observed for Fe and ERI (857) values for Cd. Soil PTEs concentrations were used to calculate the human exposure for the risk assessment, including chronic or non-carcinogenic risks such as the hazard quotient (HQ) and carcinogenic or cancer risk (CR). The values of HQ were > 1 for the Cd, Co and Cr in Khyber Pakhtunkhwa and Tribal areas. Tribal areas showed higher values of ERI, HQ, and CR as compared to the Khyber Pakhtunkhwa that were attributed to the mining activities, weathering and erosion of mafic and ultramafic bedrocks hosting ophiolites. This study strongly recommends that best control measures need to be taken for soil PTEs with the intent to alleviate any continuing potential threat to the human health, property and environment, which otherwise could enter ecosystem and ultimately the living beings. Further studies are recommended to combat the soil PTEs concentrations and toxicity in the Tribal areas for a best picture of understanding the element effects on human, and environment can be achieved that will lead to a sustainable ecological harmony.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

PubMed

Shih, Ying-Chun; Chen, Chao-Ling; Zhang, Yan; Mellor, Rebecca L; Kanter, Evelyn M; Fang, Yun; Wang, Hua-Chi; Hung, Chen-Ting; Nong, Jing-Yi; Chen, Hui-Ju; Lee, Tzu-Han; Tseng, Yi-Shuan; Chen, Chiung-Nien; Wu, Chau-Chung; Lin, Shuei-Liong; Yamada, Kathryn A; Nerbonne, Jeanne M; Yang, Kai-Chien

2018-04-13

Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting coexpression gene network analysis on RNA sequencing data from failing human heart, we identified TXNDC5 (thioredoxin domain containing 5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum protein, as a potential novel mediator of cardiac fibrosis, and we completed experiments to test this hypothesis directly. The objective of this study was to determine the functional role of TXNDC5 in the pathogenesis of cardiac fibrosis. RNA sequencing and Western blot analyses revealed that TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles and in hypertrophied/failing mouse left ventricle. In addition, cardiac TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor β1 and ECM proteins in vivo. TXNDC5 mRNA and protein were increased in human CF (hCF) under transforming growth factor β1 stimulation in vitro. Knockdown of TXNDC5 attenuated transforming growth factor β1-induced hCF activation and ECM protein upregulation independent of SMAD3 (SMAD family member 3), whereas increasing expression of TXNDC5 triggered hCF activation and proliferation and increased ECM protein production. Further experiments showed that TXNDC5, a protein disulfide isomerase, facilitated ECM protein folding and that depletion of TXNDC5 led to ECM protein misfolding and degradation in CF. In addition, TXNDC5 promotes hCF activation and proliferation by enhancing c-Jun N-terminal kinase activity via increased reactive oxygen species, derived from NAD(P)H oxidase 4. Transforming growth factor β1-induced TXNDC5 upregulation in hCF was dependent on endoplasmic reticulum stress and activating transcription factor 6-mediated transcriptional control. Targeted disruption of Txndc5 in mice ( Txndc5 -/- ) revealed protective effects against isoproterenol-induced cardiac hypertrophy, reduced fibrosis (by ≈70%), and markedly improved left ventricle function; post-isoproterenol left ventricular ejection fraction was 59.1±1.5 versus 40.1±2.5 ( P <0.001) in Txndc5 -/- versus wild-type mice, respectively. The endoplasmic reticulum protein TXNDC5 promotes cardiac fibrosis by facilitating ECM protein folding and CF activation via redox-sensitive c-Jun N-terminal kinase signaling. Loss of TXNDC5 protects against β agonist-induced cardiac fibrosis and contractile dysfunction. Targeting TXNDC5, therefore, could be a powerful new therapeutic approach to mitigate excessive cardiac fibrosis, thereby improving cardiac function and outcomes in patients with heart failure. © 2018 American Heart Association, Inc.

Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin.

PubMed

Maes, Michael; Twisk, Frank N M; Kubera, Marta; Ringel, Karl

2012-02-01

There is evidence that inflammatory pathways and cell-mediated immunity (CMI) play an important role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Activation of inflammatory and CMI pathways, including increased levels of cytokines, is known to induce fatigue and somatic symptoms. Given the broad spectrum inflammatory state in ME/CFS, the aim of this study was to examine whether inflammatory and CMI biomarkers are increased in individuals with ME/CFS. In this study we therefore measured plasma interleukin-(IL)1, tumor necrosis factor (TNF)α, and PMN-elastase, and serum neopterin and lysozyme in 107 patients with ME/CFS, 37 patients with chronic fatigue (CF), and 20 normal controls. The severity of ME/CFS was measured with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Serum IL-1, TNFα, neopterin and lysozyme are significantly higher in patients with ME/CFS than in controls and CF patients. Plasma PMN-elastase is significantly higher in patients with ME/CFS than in controls and CF patients and higher in the latter than in controls. Increased IL-1 and TNFα are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise; neopterin is correlated with fatigue, autonomic symptoms, and a flu-like malaise; and increased PMN-elastase is correlated with concentration difficulties, failing memory and a subjective experience of infection. The findings show that ME/CFS is characterized by low-grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFα. Copyright © 2011 Elsevier B.V. All rights reserved.

Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flitter, Becca A.; Hvorecny, Kelli L.; Ono, Emiko

Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognatemore » diol, eliminating a proresolving signal that potently suppresses IL-8–driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.« less

Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation.

PubMed

Mowat, Eilidh; Rajendran, Ranjith; Williams, Craig; McCulloch, Elaine; Jones, Brian; Lang, Sue; Ramage, Gordon

2010-12-01

Aspergillus fumigatus is often isolated from the lungs of cystic fibrosis (CF) patients, but unlike in severely immunocompromised individuals, the mortality rates are low. This suggests that competition from bacteria within the CF lung may be inhibitory. The purpose of this study was to investigate how Pseudomonas aeruginosa influences A. fumigatus conidial germination and biofilm formation. Aspergillus fumigatus biofilm formation was inhibited by direct contact with P. aeruginosa, but had no effect on preformed biofilm. A secreted heat-stable soluble factor was also shown to exhibit biofilm inhibition. Coculture of P. aeruginosa quorum-sensing mutants (PAO1:ΔLasI, PAO1:ΔLasR) did not significantly inhibit A. fumigatus biofilms (52.6-58.8%) to the same extent as that of the PA01 wild type (22.9-30.1%), both by direct and by indirect interaction (P<0.001). Planktonic and sessile inhibition assays with a series of short carbon chain molecules (decanol, decanoic acid and dodecanol) demonstrated that these molecules could both inhibit and disrupt biofilms in a concentration-dependent manner. Overall, this suggests that small diffusible and heat-stable molecules may be responsible for the competitive inhibition of filamentous fungal growth in polymicrobial environments such as the CF lung. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Heavy metals in industrially emitted particulate matter in Ile-Ife, Nigeria.

PubMed

Ogundele, Lasun T; Owoade, Oyediran K; Hopke, Philip K; Olise, Felix S

2017-07-01

Iron and steel smelting facilities generate large quantities of airborne particulate matter (PM) through their various activities and production processes. The resulting PM that contains a variety of heavy metals has potentially detrimental impacts on human health and the environment. This study was conducted to assess the potential health effects of the pollution from the heavy metals in the airborne PM sampled in the vicinity of secondary smelting operations in Ile-Ife, Nigeria. X-ray fluorescence (XRF) was used to determine the elemental concentration of Pb, Cr, Cd, Zn, Mn, As, Fe, Cu, and Ni in the size-segregated PM samples. Pollution Indices (PI) consisting of Contamination Factor (CF), Degree of Contamination (DC) and Pollution Index Load (PLI) and Target Hazard Quotient (THQ) were employed to assess the pollution risk associated with the heavy metals in the PM. CF, DC and PLI values were 3< CF <6, >32 and >1, respectively for the three sites, indicating deterioration of the ambient air quality in the vicinity of the smelter. The heavy metals in the airborne PM pose a severe health risk to people living in vicinity of the facility and to its workers. The diminished air quality with the associated health risks directly depends on the industrial emissions from steel production and control measures are recommended to mitigate the likely risks. Copyright © 2017 Elsevier Inc. All rights reserved.

Macroalgal blooms favor heterotrophic diazotrophic bacteria in nitrogen-rich and phosphorus-limited coastal surface waters in the Yellow Sea

NASA Astrophysics Data System (ADS)

Zhang, Xiaoli; Song, Yanjing; Liu, Dongyan; Keesing, John K.; Gong, Jun

2015-09-01

Macroalgal blooms may lead to dramatic changes in physicochemical variables and biogeochemical cycling in affected waters. However, little is known about the effects of macroalgal blooms on marine bacteria, especially those functioning in nutrient cycles. We measured environmental factors and investigated bacterial diazotrophs in two niches, surface waters that were covered (CC) and non-covered (CF) with massive macroalgal canopies of Ulva prolifera, in the Yellow Sea in the summer of 2011 using real-time PCR and clone library analysis of nifH genes. We found that heterotrophic diazotrophs (Gammaproteobacteria) dominated the communities and were mostly represented by Vibrio-related phylotypes in both CC and CF. Desulfovibrio-related phylotypes were only detected in CC. There were significant differences in community composition in these two environments (p < 0.001) and a much higher abundance of nifH in CC (4.55 × 106 copies l-1) than in CF (2.49 × 106 copies l-1). The nifH copy number was inversely related to concentrations of ammonium and dissolved inorganic nitrogen and to the stoichiometric ratios of N:P and N:Si. This indicates that macroalgal blooms significantly affect diazotrophic abundance and community composition and that vibrios and Desulfovibrio-related heterotrophic diazotrophs adapt well to the (N-rich but P-limited) environment during blooming. Potential ecological and microbiological mechanisms behind this scenario are discussed.

Growth and physiological responses of some Capsicum frutescens varieties to copper stress

NASA Astrophysics Data System (ADS)

Jadid, Nurul; Maziyah, Rizka; Nurcahyani, Desy Dwi; Mubarokah, Nilna Rizqiyah

2017-06-01

Copper (Cu) is an essential micronutrient participating in various physiological processes. However, excessive uptake of this micronutrient could potentially affect plant growth and development as well as plant productivity. In this present work, growth and physiological responses of some Capsicum frustescens varieties to Cu stress were determined. Three C. frutescens varieties used in this work were var. Bara, CF 291, and Genie. In addition, these varieties were treated with different concentration of Cu (0, 30, 70, and 120 ppm). The growth and physiological responses measured in this work included plant height, root length, malondialdehyde (MDA), and chlorophyll. The result showed that all varieties tested relatively displayed plant growth reduction including plant height and root length. Likewise, an increase of MDA level, a major bioindicator for oxidative damage was also found in all varieties following exposure to elevated Cu concentration. Finally, the chlorophyll content was also affected indicated by a decreased amount of chlorophyll, especially in var. CF291. The overall results demonstrated that elevated Cu concentration might decrease C. frutescens productivity where among the three varieties tested, var CF 291 seemed to be the most sensitive varieties to Cu stress.

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study.

PubMed

Vishnu, A; Choo, J; Masaki, K H; Mackey, R H; Barinas-Mitchell, E; Shin, C; Willcox, B J; El-Saed, A; Seto, T B; Fujiyoshi, A; Miura, K; Lee, S; Sutton-Tyrrell, K; Kuller, L H; Ueshima, H; Sekikawa, A

2014-02-01

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

Glutathione-Disrupted Biofilms of Clinical Pseudomonas aeruginosa Strains Exhibit an Enhanced Antibiotic Effect and a Novel Biofilm Transcriptome.

PubMed

Klare, William; Das, Theerthankar; Ibugo, Amaye; Buckle, Edwina; Manefield, Mike; Manos, Jim

2016-08-01

Pseudomonas aeruginosa infections result in high morbidity and mortality rates for individuals with cystic fibrosis (CF), with premature death often occurring. These infections are complicated by the formation of biofilms in the sputum. Antibiotic therapy is stymied by antibiotic resistance of the biofilm matrix, making novel antibiofilm strategies highly desirable. Within P. aeruginosa biofilms, the redox factor pyocyanin enhances biofilm integrity by intercalating with extracellular DNA. The antioxidant glutathione (GSH) reacts with pyocyanin, disrupting intercalation. This study investigated GSH disruption by assaying the physiological effects of GSH and DNase I on biofilms of clinical CF isolates grown in CF artificial sputum medium (ASMDM+). Confocal scanning laser microscopy showed that 2 mM GSH, alone or combined with DNase I, significantly disrupted immature (24-h) biofilms of Australian epidemic strain (AES) isogens AES-1R and AES-1M. GSH alone greatly disrupted mature (72-h) AES-1R biofilms, resulting in significant differential expression of 587 genes, as indicated by RNA-sequencing (RNA-seq) analysis. Upregulated systems included cyclic diguanylate and pyoverdine biosynthesis, the type VI secretion system, nitrate metabolism, and translational machinery. Biofilm disruption with GSH revealed a cellular physiology distinct from those of mature and dispersed biofilms. RNA-seq results were validated by biochemical and quantitative PCR assays. Biofilms of a range of CF isolates disrupted with GSH and DNase I were significantly more susceptible to ciprofloxacin, and increased antibiotic effectiveness was achieved by increasing the GSH concentration. This study demonstrated that GSH, alone or with DNase I, represents an effective antibiofilm treatment when combined with appropriate antibiotics, pending in vivo studies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Glutathione-Disrupted Biofilms of Clinical Pseudomonas aeruginosa Strains Exhibit an Enhanced Antibiotic Effect and a Novel Biofilm Transcriptome

PubMed Central

Das, Theerthankar; Ibugo, Amaye; Buckle, Edwina; Manefield, Mike; Manos, Jim

2016-01-01

Pseudomonas aeruginosa infections result in high morbidity and mortality rates for individuals with cystic fibrosis (CF), with premature death often occurring. These infections are complicated by the formation of biofilms in the sputum. Antibiotic therapy is stymied by antibiotic resistance of the biofilm matrix, making novel antibiofilm strategies highly desirable. Within P. aeruginosa biofilms, the redox factor pyocyanin enhances biofilm integrity by intercalating with extracellular DNA. The antioxidant glutathione (GSH) reacts with pyocyanin, disrupting intercalation. This study investigated GSH disruption by assaying the physiological effects of GSH and DNase I on biofilms of clinical CF isolates grown in CF artificial sputum medium (ASMDM+). Confocal scanning laser microscopy showed that 2 mM GSH, alone or combined with DNase I, significantly disrupted immature (24-h) biofilms of Australian epidemic strain (AES) isogens AES-1R and AES-1M. GSH alone greatly disrupted mature (72-h) AES-1R biofilms, resulting in significant differential expression of 587 genes, as indicated by RNA-sequencing (RNA-seq) analysis. Upregulated systems included cyclic diguanylate and pyoverdine biosynthesis, the type VI secretion system, nitrate metabolism, and translational machinery. Biofilm disruption with GSH revealed a cellular physiology distinct from those of mature and dispersed biofilms. RNA-seq results were validated by biochemical and quantitative PCR assays. Biofilms of a range of CF isolates disrupted with GSH and DNase I were significantly more susceptible to ciprofloxacin, and increased antibiotic effectiveness was achieved by increasing the GSH concentration. This study demonstrated that GSH, alone or with DNase I, represents an effective antibiofilm treatment when combined with appropriate antibiotics, pending in vivo studies. PMID:27161630

Peritoneal Cell-free DNA: an innovative method for determining acute cell damage in peritoneal membrane and for monitoring the recovery process after peritonitis.

PubMed

Virzì, Grazia Maria; Milan Manani, Sabrina; Brocca, Alessandra; Cantaluppi, Vincenzo; de Cal, Massimo; Pastori, Silvia; Tantillo, Ilaria; Zambon, Roberto; Crepaldi, Carlo; Ronco, Claudio

2016-02-01

Cell-free DNA (cfDNA) is present in the peritoneal effluent of stable peritoneal dialysis (PD) patients, but there are no data on cfDNA in PD patients with peritonitis. We investigated the variation of peritoneal cfDNA levels subsequent to peritonitis in PD patients. We enrolled 53 PD patients: 30 without any history of systemic inflammation or peritonitis in the last 3 months (group A) and 23 with acute peritonitis (group B). CfDNA was quantified in the peritoneal effluent. Peritoneal samples on days 1, 3, 10, 30 and until day 120 from the start of peritonitis were collected for white blood cells (WBC) count and cfDNA evaluation in group B. Quantitative analysis of cfDNA showed significantly higher levels in group B on day 1, 3, 10 and 30 compared with group A (p < 0.05). A significant positive correlation was observed between cfDNA concentration and WBC on day 1 (rho = 0.89) and day 3 (rho = 0.5) (both, p < 0.05). However, no significant correlation was observed between cfDNA and WBC on days 10 and 30. In group B, peritoneal cfDNA levels tended to progressively decline during follow-up of peritonitis. From this decreasing curve, we estimated that 49 days are necessary to reach the value of 51 genome equivalents (GE)/ml (75th percentile in controls) and 63 days to reach 31 GE/ml (median). Our results demonstrate that cfDNA increases in peritoneal effluent of PD patients with peritonitis and tends to progressively decline in step with peritonitis resolution and membrane repair process. Peritoneal cfDNA quantification could be an innovative method to determine acute damage and an inverse index of the repair process.

Multifunctional Hybrid Carbon Nanotube/Carbon Fiber Polymer Composites

NASA Technical Reports Server (NTRS)

Kang, Jin Ho; Cano, Roberto J.; Ratcliffe, James G.; Luong, Hoa; Grimsley, Brian W.; Siochi, Emilie J.

2016-01-01

For aircraft primary structures, carbon fiber reinforced polymer (CFRP) composites possess many advantages over conventional aluminum alloys due to their light weight, higher strengthand stiffness-to-weight ratio, and low life-cycle maintenance costs. However, the relatively low electrical and thermal conductivities of CFRP composites fail to provide structural safety in certain operational conditions such as lightning strikes. Despite several attempts to solve these issues with the addition of carbon nanotubes (CNT) into polymer matrices, and/or by interleaving CNT sheets between conventional carbon fiber (CF) composite layers, there are still interfacial problems that exist between CNTs (or CF) and the resin. In this study, hybrid CNT/CF polymer composites were fabricated by interleaving layers of CNT sheets with Hexcel® IM7/8852 prepreg. Resin concentrations from 1 wt% to 50 wt% were used to infuse the CNT sheets prior to composite fabrication. The interlaminar properties of the resulting hybrid composites were characterized by mode I and II fracture toughness testing (double cantilever beam and end-notched flexure test). Fractographical analysis was performed to study the effect of resin concentration. In addition, multi-directional physical properties like thermal conductivity of the orthotropic hybrid polymer composite were evaluated. Interleaving CNT sheets significantly improved the in-plane (axial and perpendicular direction of CF alignment) thermal conductivity of the hybrid composite laminates by 50 - 400%.

Simulation of mechano-electrical transduction in the cochlea considering basilar membrane vibration and the ionic current of the inner hair cells

NASA Astrophysics Data System (ADS)

Lee, Sinyoung; Koike, Takuji

2018-05-01

The inner hair cells (IHCs) in the cochlea transduce mechanical vibration of the basilar membrane (BM), caused by sound pressure, to electrical signals that are transported along the acoustic nerve to the brain. The mechanical vibration of the BM and the ionic behaviors of the IHCs have been investigated. However, consideration of the ionic behavior of the IHCs related to mechanical vibration is necessary to investigate the mechano-electrical transduction of the cochlea. In this study, a finite-element model of the BM, which takes into account the non-linear activities of the outer hair cells (OHCs), and an ionic current model of IHC were combined. The amplitudes and phases of the vibration at several points on the BM were obtained from the finite-element model by applying sound pressure. These values were fed into the ionic current model, and changes in membrane potential and calcium ion concentration of the IHCs were calculated. The membrane potential of the IHC at the maximum amplitude point (CF point) was higher than that at the non-CF points. The calcium ion concentration at the CF point was also higher than that at the non-CF points. These results suggest that the cochlea achieves its good frequency discrimination ability through mechano-electrical transduction.

High-sensitivity sucrose erbium-doped fiber ring laser sensor

NASA Astrophysics Data System (ADS)

Khaleel, Wurood Abdulkhaleq; Al-Janabi, Abdul Hadi M.

2017-02-01

We investigate a high-sensitivity sucrose sensor based on a standard erbium-doped fiber ring laser incorporating a coreless fiber (CF). A single-mode-coreless-single mode (SCS) structure with a very low insertion loss has been constructed. The SCS fiber structure performed dual function as an intracavity fiber filter and/or a sensing element. The gain medium (erbium-doped fiber) is pumped by a 975-nm wavelength fiber coupled diode laser. Laser emission around 1537 nm with -2 dBm peak output power is obtained when a CF in SCS structure has a diameter of 125 μm. The 3-dB line-width of the laser is <0.14 nm, which is beneficial to high precision sensing. The sucrose concentration varied from 0% to 60%, and the relationship between the lasing wavelength and the sucrose concentration exhibited linear behavior (R2=0.996), with sensitivity of 0.16 nm/% was obtained. To improve the measurement sensitivity, the CF is etched by hydrofluoric acid. The splice joint of etched CF with SMF is a taper, which improves its sensitivity to sucrose changes. An average sensitivity of 0.57 nm/% and a high signal-to-noise ratio of 50 dB make the proposed sensor suitable for potential applications.

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

PubMed Central

2014-01-01

SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced. PMID:25278574

Carbon footprint and land requirement for dairy herd rations: impacts of feed production practices and regional climate variations.

PubMed

Henriksson, M; Cederberg, C; Swensson, C

2014-08-01

Feed production is a significant source of greenhouse gas (GHG) emissions from dairy production and demands large arable and pasture acreage. This study analysed how regional conditions influence GHG emissions of dairy feed rations in a life cycle perspective, that is the carbon footprint (CF) and the land area required. Factors assessed included regional climate variations, grass/clover silage nutrient quality, feedstuff availability, crop yield and feed losses. Using the Nordic feed evaluation model NorFor, rations were optimised for different phases of lactation, dry and growing periods for older cows, first calvers and heifers by regional feed advisors and combined to annual herd rations. Feed production data at farm level were based on national statistics and studies. CF estimates followed standards for life cycle assessment and used emissions factors provided by IPCC. The functional unit was 'feed consumption to produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9 900 kg ECM including replacement animals and feed losses'. Feed ration CF varied from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of total GHG emissions. Use of higher quality silage increased ration CF by up to 5% as a result of an additional cut and increased rates of synthetic N-fertiliser. Domestically produced horse bean (Vicia faba), by-products from the sugar industry and maize silage were included in the rations with the lowest CF, but horse bean significantly increased ration land requirement. Rations required between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG emissions from land use change associated with Brazilian soya feed significantly increased ration CF. Ration CF and land use depended on ration composition, which was highly influenced by the regional availability and production of feedstuffs. The impact of individual feedstuffs on ration CF varies due to, for example, cultivation practices and climate conditions and feedstuffs should therefore be assessed in a ration and regional perspective before being used to decrease milk CF. Land use efficiency should be considered together with ration CF, as these can generate goal conflicts.

Cystic Fibrosis and Its Management Through Established and Emerging Therapies.

PubMed

Spielberg, David R; Clancy, John P

2016-08-31

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes.

High incidence of non-tuberculous mycobacteria-positive cultures among adolescent with cystic fibrosis.

PubMed

Cavalli, Zoé; Reynaud, Quitterie; Bricca, Romain; Nove-Josserand, Raphaële; Durupt, Stéphane; Reix, Philippe; Perceval, Marie; de Montclos, Michèle Pérouse; Lina, Gérard; Durieu, Isabelle

2017-09-01

We evaluated the prevalence of non-tuberculous mycobacteria (NTM)-positive cultures among our cystic fibrosis (CF) center patients, reviewed risk factors for NTM positivity, and determined its impact on lung function evolution. From 2009 to 2014, CF adults and children attending the CF center of Lyon (France) and having at least one positive NTM isolate were included. Each case was matched by age and gender with two CF patients with no NTM isolate (controls). 48 CF patients with NTM-positive isolates were matched to 96 controls. The age group for whom incident NTM was higher was young adolescents aged 13 to 17. A significant association for NTM positivity was found with Staphylococcusaureus in multivariate analysis and with allergic bronchopulmonary aspergillosis, corticosteroid and itraconazole in univariate analysis. Mean annual FEV1 decline was faster for NTM-positive patients compared to controls. These data highlight the high incidence of NTM-positive cultures among young adolescents with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

PubMed

Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel

2017-11-27

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

The 3849 + 10 kB C-->T mutation in a 21-year-old patient with cystic fibrosis.

PubMed

Kaplan, D M; Niv, A; Aviram, M; Parvari, R; Leiberman, A; Fliss, D M

1996-12-01

Cystic fibrosis (CF) is the most common lethal inherited disease in the white population. It is characterized by exocrine gland epithelia dysfunction, which leads to pulmonary and pancreatic insufficiency. Since the cloning of the CF gene in 1989 and the identification of the most common CF mutation (delta F508), more than 400 different mutations have been described. These mutations appear to contribute to the heterogeneity of the CF phenotype and several reports have speculated on the relationship between the most common CF mutations and the patient's clinical status. We report the case of a 21-year-old woman with longstanding chronic pansinusitis, nasal polyposis, chronic cough and severe nasal crusting. During a period of five years she had been followed by her otolaryngologist and pediatric pulmonologist. Sweat tests performed at the age of 17 and 18 were within normal limits and she underwent repeated conventional sinonasal procedures, with no improvement in her clinical status. On her present admission, sweat tests showed a 70 meq/l chloride concentration. The diagnosis of CF was then confirmed by DNA analysis and the patient was found to carry the 3849 + 10 kB C-->T mutation. The early detection of this newly recognized form of CF in adults as well as in children presenting with sinonasal symptoms is critical for life expectancy and quality.

In situ CF3 Detection in Low Pressure Inductive Discharges by Fourier Transform Infrared Spectroscopy

NASA Technical Reports Server (NTRS)

Kim, J. S.; Cappelli, M. A.; Sharma, S. P.; Arnold, J. O. (Technical Monitor)

1998-01-01

The detection of CF(x) (x=1-3) radicals in low pressure discharges using source gases such as CF4 and CHF3 is of importance to the understanding of their chemical structure and relevance in plasma based etching processes. These radicals are known to contribute to the formation of fluorocarbon polymer films, which affect the selectivity and anisotropy of etching. In this study, we present preliminary results of the quantitative measurement of trifluoromethyl radicals, CF3, in low pressure discharges. The discharge studied here is an inductively (transformer) coupled plasma (ICP) source in the GEC reference cell, operating on pure CF4 at pressures ranging from 10 - 100 mTorr, This plasma source generates higher electron number densities at lower operating pressures than obtainable with the parallel-plate capacitively coupled version of the GEC reference cell. Also, this expanded operating regime is more relevant to new generations of industrial plasma reactors being used by the microelectronics industry. Fourier transform infrared (FTIR) spectroscopy is employed to observe the absorption band of CF3 radicals in the electronic ground state X2Al in the region of 1233-1270/cm. The spectrometer is equipped with a high sensitivity HgCdTe (MCT) detector and has a fixed resolution of 0.125/cm. The CF3 concentrations are measured for a range of operating pressures and discharge power levels.

Defective innate immunity and hyperinflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs.

PubMed

Keiser, Nicholas W; Birket, Susan E; Evans, Idil A; Tyler, Scott R; Crooke, Adrianne K; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R; Stroebele, Elizabeth K; Chu, Kengyeh K; Tearney, Guillermo J; Stevens, Mark J; Harris, J Kirk; Rowe, Steven M; Engelhardt, John F

2015-06-01

Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography-tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals.

Defective Innate Immunity and Hyperinflammation in Newborn Cystic Fibrosis Transmembrane Conductance Regulator–Knockout Ferret Lungs

PubMed Central

Keiser, Nicholas W.; Birket, Susan E.; Evans, Idil A.; Tyler, Scott R.; Crooke, Adrianne K.; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R.; Stroebele, Elizabeth K.; Chu, Kengyeh K.; Tearney, Guillermo J.; Stevens, Mark J.; Harris, J. Kirk; Rowe, Steven M.

2015-01-01

Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography–tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals. PMID:25317669

Atrial rhythm influences catheter tissue contact during radiofrequency catheter ablation of atrial fibrillation: comparison of contact force between sinus rhythm and atrial fibrillation.

PubMed

Matsuda, Hisao; Parwani, Abdul Shokor; Attanasio, Philipp; Huemer, Martin; Wutzler, Alexander; Blaschke, Florian; Haverkamp, Wilhelm; Boldt, Leif-Hendrik

2016-09-01

Catheter tissue contact force (CF) is an important factor for durable lesion formation during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Since CF varies in the beating heart, atrial rhythm during RFCA may influence CF. A high-density map and RFCA points were obtained in 25 patients undergoing RFCA of AF using a CF-sensing catheter (Tacticath, St. Jude Medical). The operators were blinded to the CF information. Contact type was classified into three categories: constant, variable, and intermittent contact. Average CF and contact type were analyzed according to atrial rhythm (SR vs. AF) and anatomical location. A total of 1364 points (891 points during SR and 473 points during AF) were analyzed. Average CFs showed no significant difference between SR (17.2 ± 11.3 g) and AF (17.2 ± 13.3 g; p = 0.99). The distribution of points with an average CF of ≥20 and <10 g also showed no significant difference. However, the distribution of excessive CF (CF ≥40 g) was significantly higher during AF (7.4 %) in comparison with SR (4.2 %; p < 0.05). At the anterior area of the right inferior pulmonary vein (RIPV), the average CF during AF was significantly higher than during SR (p < 0.05). Constant contact was significantly higher during AF (32.2 %) when compared to SR (9.9 %; p < 0.01). Although the average CF was not different between atrial rhythms, constant contact was more often achievable during AF than it was during SR. However, excessive CF also seems to occur more frequently during AF especially at the anterior part of RIPV.

Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size.

PubMed

Ikeda, Atsushi; Nakagawa, Hiroshi; Lambert, Hendrik; Shah, Dipen C; Fonck, Edouard; Yulzari, Aude; Sharma, Tushar; Pitha, Jan V; Lazzara, Ralph; Jackman, Warren M

2014-12-01

Electrode-tissue contact force (CF) is believed to be a major factor in radiofrequency lesion size. The purpose of this study was to determine, in the beating canine heart, the relationship between CF and radiofrequency lesion size and the accuracy of predicting CF and lesion size by measuring electrogram amplitude, impedance, and electrode temperature. Eight dogs were studied closed chest. Using a 7F catheter with a 3.5 mm irrigated electrode and CF sensor (TactiCath, St. Jude Medical), radiofrequency applications were delivered to 3 separate sites in the right ventricle (30 W, 60 seconds, 17 mL/min irrigation) and 3 sites in the left ventricle (40 W, 60 seconds, 30 mL/min irrigation) at (1) low CF (median 8 g); (2) moderate CF (median 21 g); and (3) high CF (median 60 g). Dogs were euthanized and lesion size was measured. At constant radiofrequency and time, lesion size increased significantly with increasing CF (P<0.01). The incidence of a steam pop increased with both increasing CF and higher power. Peak electrode temperature correlated poorly with lesion size. The decrease in impedance during the radiofrequency application correlated well with lesion size for lesions in the left ventricle but less well for lesions in the right ventricle. There was a poor relationship between CF and the amplitude of the bipolar or unipolar ventricular electrogram, unipolar injury current, and impedance. Radiofrequencylesion size and the incidence of steam pop increase strikingly with increasing CF. Electrogram parameters and initial impedance are poor predictors of CF for radiofrequency ablation. © 2014 American Heart Association, Inc.

Self-efficacy: empowering parents of children with cystic fibrosis.

PubMed

McDonald, Catherine M; Haberman, Diane; Brown, Natalie

2013-09-01

Can parent engagement in the development and delivery of educational materials for cystic fibrosis (CF) promote increased self-efficacy and confidence in self-management skills? Standard therapies for a child with CF frequently involve pulmonary treatment, medications, and behavioral and nutritional interventions. Parents report that the prescribed CF care can be overwhelming. Previous research at this pediatric CF Center indicated the parental perception of the difficulty in managing CF-related nutrition therapy. Parents' nutrition knowledge was an initial target of this continuous quality improvement (CQI) project with a long-range aim of increasing children's median body mass index (BMI) percentiles for patients at this pediatric CF center. The local CF Parent Advisory Council, CF parents and staff collaborated on this family-centered CQI project. A CF parent website with weekly email newsletters and a facebook page were developed and evolved with input from parents. Parental feedback was gathered through electronic surveys, written questionnaires, focus groups and informal interviews. A convenience sample of parents participated in pre- and post-intervention surveys to determine change in self-confidence in effectively managing their children's CF treatment regimens. Results were also compared with responses from a larger previous survey. Parental knowledge of nutrition facts and medical nutrition therapy for CF did not increase significantly over the course of the CQI project. Surveyed parents reported increased confidence in their self-management skills. Although mean BMI percentiles have increased at this center, they remain below the national average. Parent-driven educational strategies provide an opportunity to promote reliable CF-related information in parent-preferred formats that enhance self-management skills in caring for children with CF. Parental confidence to follow CF center recommendations increased between 2004 and 2011. Although many factors may impact confidence, parent satisfaction with the creation of electronic resources and engagement in the CQI process were intangible, but important outcomes. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Baseline predictors of aortic stiffness progression among multi-ethnic Asians with type 2 diabetes.

PubMed

Moh, Mei Chung; Sum, Chee Fang; Tavintharan, Subramaniam; Ang, Keven; Lee, Simon Biing Ming; Tang, Wern Ee; Lim, Su Chi

2017-05-01

This 3-year prospective study aimed to identify baseline parameters that predicted the progression of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness, among Singapore's multi-ethnic Asians with type 2 diabetes (T2DM). The cf-PWV was measured by the gold-standard tonometry method in 994 T2DM subjects at baseline and follow-up. The annual rate of cf-PWV change was calculated, and individuals above the 90 th percentile with rate≥1.42 m/s per year were regarded as rapid progressors (n = 104). In a subgroup analysis of subjects with normal cf-PWV at 1 st visit (n = 611), incident aortic stiffness was defined as follow-up cf-PWV≥10 m/s (n = 188). The total cohort (mean age:57 ± 10 years; 53.4% Chinese, 20.4% Malay, 22.9% Indian, 3.2% 'Others') displayed a median annual cf-PWV progression rate of 0.2 m/s. Adjusted multivariate regression analyses showed that baseline age, cf-PWV and body mass index (BMI) constantly predicted follow-up cf-PWV, annual cf-PWV progression rate, rapid cf-PWV progression, and incident aortic stiffness. Paradoxically, lower baseline cf-PWV was associated with elevated annual cf-PWV progression rate and rapid progressors. This inverse relationship remained significant across ethnicities after ethnic stratification. Higher BMI independently predicted cf-PWV progression in Chinese and Indians, but not in Malay and 'Others' ethnic groups. Increased age was a significant predictor in Chinese and 'Others' ethnicities. We demonstrated that baseline BMI is a modifiable independent risk factor of cf-PWV progression and incident aortic stiffness. Therefore, better obesity management may impede aortic stiffness in Singapore's T2DM patients, especially in the Chinese and Indians. Copyright © 2017. Published by Elsevier B.V.

Genetic and Environmental Influences on Disability Pension Due To Mental Diagnoses: Limited Importance of Major Depression, Generalized Anxiety, and Chronic Fatigue.

PubMed

Narusyte, Jurgita; Ropponen, Annina; Alexanderson, Kristina; Svedberg, Pia

2016-02-01

Previous research indicates that liability to disability pension (DP) due to mental diagnoses is moderately influenced by genetic factors. This study investigates whether genetic contributions to the liability to DP due to mood and neurotic diagnoses overlap with the genetic influences on major depression (MD), generalized anxiety disorder (GAD), or chronic fatigue (CF). A prospective cohort study including 9,985 female twins born in Sweden 1933-1958. The presence of MD, GAD, and CF was assessed by computer-assisted telephone interviews conducted in 1998-2002. Data on DP due to mood and neurotic diagnoses were obtained from nationwide registers for the years 1998-2010. Common genetic and environmental influences on the phenotypes were estimated by applying structural equation modeling. The prevalence of MD/GAD was 30%, CF 8%, and DP due to mood and neurotic diagnoses 3% in 2010. Genetic effects on MD/GAD explained 31% of the total genetic variation in DP, whereas genetic contributions in common with CF were small and not significant. The majority of the total non-shared environmental variance in DP (85%) was explained by the factors that were unique to DP. Large proportions of genetic and non-shared environmental influences in DP due to mood and neurotic diagnoses were not explained by the contributions from MD/GAD or CF. The results suggest that the process leading to DP is complex and influenced by factors other than those related to the disorder underlying DP.

Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer.

PubMed

Chan, Elisa K; Woods, Ryan; Virani, Sean; Speers, Caroline; Wai, Elaine S; Nichol, Alan; McBride, Mary L; Tyldesley, Scott

2015-01-01

Ongoing concern remains regarding cardiac injury with hypofractionated whole breast/chest-wall radiotherapy (HF-WBI) compared to conventional radiotherapy (CF-WBI) in left-sided breast cancer patients. The purpose was to determine if cardiac mortality increases with HF-WBI relative to CF-WBI. Between 1990 and 1998, 5334 women with early-stage breast cancer received post-operative radiotherapy to the breast/chest wall alone. A population-based database recorded baseline patient, tumor and treatment factors. Baseline cardiovascular risk factors were identified from hospital administrative records. A propensity-score model balanced risk factors between radiotherapy groups. Cause of death was coded as breast cancer, cardiac or other cause. Cumulative mortality from each cause after radiotherapy was estimated using a competing risk approach. For left-sided cases, median follow-up was 14.2 years. 485 women received CF-WBI, 2221 women received HF-WBI. There was no difference in 15-year mortality from cardiac causes: 4.8% with HF-WBI and 4.2% with CF-WBI (p=0.74), even after propensity-score adjustment (p=0.45). There was no difference in breast cancer mortality or other cause mortality. For right-sided cases, there was no difference in mortality for the three causes of death. At 15-years follow-up, cardiac mortality is not statistically different among left-sided breast cancer patients treated with HF-WBI or CF-WBI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Surface modification of epoxy resin using He/CF4 atmospheric pressure plasma jet for flashover withstanding characteristics improvement in vacuum

NASA Astrophysics Data System (ADS)

Chen, Sile; Wang, Shuai; Wang, Yibo; Guo, Baohong; Li, Guoqiang; Chang, Zhengshi; Zhang, Guan-Jun

2017-08-01

For enhancing the surface electric withstanding strength of insulating materials, epoxy resin (EP) samples are treated by atmospheric pressure plasma jet (APPJ) with different time interval from 0 to 300s. Helium (He) and tetrafluoromethane (CF4) mixtures are used as working gases with the concentration of CF4 ranging 0%-5%, and when CF4 is ∼3%, the APPJ exhibits an optimal steady state. The flashover withstanding characteristics of modified EP in vacuum are greatly improved under appropriate APPJ treatment conditions. The surface properties of EP samples are evaluated by surface roughness, scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS) and water contact angle. It is considered that both physical and chemical effects lead to the enhancement of flashover strength. The physical effect is reflected in the increase of surface roughness, while the chemical effect is reflected in the graft of fluorine groups.

Kinetic parameters of rubidium transport pathways are normal in cystic fibrosis red cells.

PubMed

Joiner, C H

1988-10-01

The abnormalities in ion transport in cystic fibrosis (CF) respiratory and sweat duct epithelia have prompted studies of ion permeability in CF red blood cells (RBC) although previous reports have been contradictory. In this study, the kinetic characteristics of the three major cation transport systems in RBC were evaluated by measuring rubidium (Rb) uptake at various external Rb concentrations. The maximal velocity and affinity for external Rb (K1/2) of the NaK pump were normal in CF RBC, as were the maximal velocity and Km for Rb of the NaK cotransport system. Residual (ouabain and bumetanide insensitive) Rb uptake, and steady state RBC Na and K contents were also normal. These data indicate the NaK pump and cotransport system do not exhibit primary or secondary perturbations in CF RBC, and suggest that the noncarrier-mediated membrane permeability to cations is also normal in these cells.

TU-H-CAMPUS-IeP1-03: Comparison of Monte Carlo Simulation and Conversion Factor Based Method On Estimation of Effective Dose in Pediatric Patients Undergoing Interventional Cardiac Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leung, K; Wong, M; Ng, Y

Purpose: Interventional cardiac procedures utilize frequent fluoroscopy and cineangiography, which impose considerable radiation risk to patients, especially pediatric patients. Accurate calculation of effective dose is important in order to estimate cancer risk over the rest of their lifetime. This study evaluates the difference in effective dose calculated by Monte Carlo simulation with those estimated by locally-derived conversion factors (CF-local) and by commonly quoted conversion factors from Karambatsakidou et al (CF-K). Methods: Effective dose (E),of 12 pediatric patients, age between 2.5–19 years old, who had undergone interventional cardiac procedures, were calculated using PCXMC-2.0 software. Tube spectrum, irradiation geometry, exposure parameters andmore » dose-area product (DAP) of each projection were included in the software calculation. Effective doses for each patient were also estimated by two Methods: 1) CF-local: conversion factor derived locally by generalizing results of 12 patients, multiplied by DAP of each patient gives E-local. 2) CF-K: selected factor from above-mentioned literature, multiplied by DAP of each patient gives E-K. Results: Mean of E, E-local and E-K were 16.01 mSv, 16.80 mSv and 22.25 mSv respectively. A deviation of −29.35% to +34.85% between E and E-local, while a greater deviation of −28.96% to +60.86% between E and EK were observed. E-K overestimated the effective dose for patients at age 7.5–19. Conclusion: Effective dose obtained by conversion factors is simple and quick to estimate radiation risk of pediatric patients. This study showed that estimation by CF-local may bear an error of 35% when compared with Monte Carlo calculation. If using conversion factors derived by other studies may result in an even greater error, of up to 60%, due to factors that are not catered for in the estimation, including patient size, projection angles, exposure parameters, tube filtration, etc. Users must be aware of these potential inaccuracies when simple conversion method is employed.« less

The effect of acute and chronic exercise on cognitive function and academic performance in adolescents: A systematic review.

PubMed

Li, Joanna W; O'Connor, Helen; O'Dwyer, Nicholas; Orr, Rhonda

2017-09-01

To investigate whether exercise, proposed to enhance neuroplasticity and potentially cognitive function (CF) and academic performance (AP), may be beneficial during adolescence when important developmental changes occur. Systematic review evaluating the impact of acute or chronic exercise on CF and AP in adolescents (13-18 years). Nine databases (AMED, AusportMed, CINAHL, COCHRANE, Embase, Medline, Scopus, SPORTdiscus, Web of Science) were searched from earliest records to 31st October 2016, using keywords related to exercise, CF, AP and adolescents. Eligible studies included controlled trials examining the effect of any exercise intervention on CF, AP or both. Effect size (ES) (Hedges g) were calculated where possible. Ten papers (11 studies) were reviewed. Cognitive domains included: executive function (n=4), memory (n=4), attention/concentration (n=2), visuo-motor speed (n=1), logical sequencing (n=1) and psychometric aptitude (n=1). All papers, nine of 10 being acute studies, reported at least one parameter showing a significant effect of exercise in improving CF and AP. However, the CF parameters displayed substantial heterogeneity, with only 37% favouring acute and chronic exercise. Where ES could be calculated, 52% of the acute CF parameters favoured rest. Memory was the domain most consistently improved by exercise. Academic performance demonstrated a significant improvement with exercise in one of two acute studies and the only chronic study (p≤0.001). The evidence for the effect of exercise on CF and AP in adolescents is equivocal and limited in quantity and quality. Well-designed research is therefore warranted to determine the benefits of exercise in enhancing CF and AP and reducing sedentary behaviour. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Screening method to evaluate point-of-care human chorionic gonadotropin (hCG) devices for susceptibility to the hook effect by hCG β core fragment: evaluation of 11 devices.

PubMed

Nerenz, Robert D; Song, Haowei; Gronowski, Ann M

2014-04-01

The predominant hCG variant in urine, hCG β core fragment (hCGβcf), has been demonstrated to cause false-negative results in qualitative point-of-care (POC) hCG devices. This is a major concern for healthcare professionals using POC pregnancy tests. We developed a screening method to evaluate qualitative POC hCG devices for their susceptibility to inhibition by hCGβcf. Using this method, we evaluated the performance of 11 commonly used devices. A wide range of purified hCG and hCGβcf concentrations were mixed and tested on 2 POC devices. By use of those results, a screening method was defined and 9 additional POC devices were evaluated. Two solutions containing (a) 500 pmol/L (171 IU/L) intact hCG with 0 pmol/L hCGβcf and (b) 500 pmol/L intact hCG with 500 000 pmol/L hCGβcf were used to screen all POC devices. The OSOM and Cen-Med Elite devices were found to be most susceptible to false-negative results due to hCGβcf. The BC Icon 20 and the Alere were the least susceptible. The remaining 7 were moderately affected. Devices that gave the strongest signal with hCGβcf alone were those that were least likely to show a hook effect. The screening method put forth here can be used by device users and manufacturers to evaluate POC devices for inhibition by hCGβcf. Of 11 devices evaluated, only 2 have been identified that exhibit minimal to no susceptibility to hCGβcf.

Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent.

PubMed

Schuch, Raymond; Khan, Babar K; Raz, Assaf; Rotolo, Jimmy A; Wittekind, Michael

2017-07-01

Biofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to target Staphylococcus aureus biofilms. We used minimum biofilm-eradicating concentration (MBEC) assays on 95 S. aureus strains to obtain a 90% MBEC (MBEC 90 ) value of ≤0.25 μg/ml for CF-301. Mature biofilms of coagulase-negative staphylococci, Streptococcus pyogenes , and Streptococcus agalactiae were also sensitive to disruption, with MBEC 90 values ranging from 0.25 to 8 μg/ml. The potency of CF-301 was demonstrated against S. aureus biofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed by S. aureus and Staphylococcus epidermidis on several surfaces, were removed by CF-301, as were S. aureus biofilms either enriched for small-colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated against S. aureus persister cells in exponential-phase and stationary-phase populations. Finally, the antibiofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range of S. aureus strains. In all, the data show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component. Copyright © 2017 American Society for Microbiology.

Occurrence, distribution, and attenuation of pharmaceuticals and personal care products in the riverside groundwater of the Beiyun River of Beijing, China.

PubMed

Yang, Lei; He, Jiang-Tao; Su, Si-Hui; Cui, Ya-Feng; Huang, De-Liang; Wang, Guang-Cai

2017-06-01

This study investigated the occurrence, seasonal-spatial distribution characteristics, and attenuation process of 15 pharmaceuticals and personal care products (PPCPs) in riverside sections of Beiyun River of Beijing. The overall PPCP levels both in surface water and riverside groundwater were moderate on the global scale, and showed higher concentrations in the dry season mainly caused by water temperature variation. Caffeine (CF), carbamazepine (CBZ), metoprolol (MTP), N,N-diethyl-meta-toluamide (DEET), diclofenac (DF), bezafibrate (BF), and gemfibrozil (GF) were seven representative PPCPs, because the rest eight studied compounds occurred in low concentrations and less than 15% of the total concentration of PPCPs. Caffeine and bezafibrate, respectively, was the most abundant compound in surface water and riverside groundwater, with median concentrations of 3020.0 and 125.0 ng L -1 . Total concentrations of PPCPs in surface water were much higher than those in the riverside groundwater spatially. Attenuation of PPCPs during riverbank filtration was largely depending on the sources, site hydrogeological conditions, and physical-chemical properties of PPCPs, also was influenced by dissolved organic matter and environmental physicochemical parameters. CF, MTP, DEET, and CBZ were potential groundwater attenuation contaminants; DF, BF, and GF were groundwater-enriched contaminants based on their removal rates. Predominant removal mechanism of PPCPs like CF was biodegradation. Attenuation simulation showed that the one-way supply between Beiyun River and riverside groundwater, and further confirmed Beiyun River, was the main source of pharmaceutical compounds in the riverside groundwater.

Validation of the Compassion Fatigue Short Scale among Chinese medical workers and firefighters: a cross-sectional study

PubMed Central

Sun, Binghai; Hu, Mengna; Yu, Shitian; Jiang, Yiru; Lou, Baona

2016-01-01

Objectives To examine the psychometric properties of the Chinese version of the C-Compassion Fatigue (CF)-Short Scale among 4 independent samples of Chinese emergency workers (medical workers and firefighters). Design Cross-sectional. Setting 6 hospitals in Zhejiang Province and 12 fire stations in Shanghai. Participants Emergency workers (medical and firefighters) were consecutively recruited and divided into 4 groups: the MW1 group (medical workers, n=167), the FF1 group (firefighters, n=157), the MW2 group (medical workers, n=265) and the FF2 group (firefighters, n=231). Interventions All patients completed the C-CF-Short Scale to identify factors associated with compassion fatigue. The MW1 and FF1 groups were used for the exploratory analyses. The MW2 and FF2 groups were used for the confirmatory factor analyses. Primary and secondary outcome measures Factor loading, correlations with previously validated questionnaires (the Ego-Resiliency Scale, the Social Support Questionnaire and the Job Pressure Scale) and Cronbach's α coefficient were tested for each factor. Results The C-CF-Short Scale demonstrated excellent construct validity and good internal consistency. Specifically, the results of exploratory factor analyses in the MW1 and FF1 groups showed that secondary trauma and job burnout were associated with compassion fatigue in these emergency workers. The confirmatory factor analyses in the MW2 and FF2 groups indicated that all the fit indices of the 2-factor model were satisfactory. Finally, the Cronbach's α coefficient of each factor was excellent. Conclusions The findings suggest that the C-CF-Short Scale has good psychometric properties and can be applied to study Chinese emergency workers. PMID:27363817

Pharmacokinetics of Tedizolid in Plasma and Sputum of Adults with Cystic Fibrosis.

PubMed

Park, A Young J; Wang, Joshua; Jayne, Jordanna; Fukushima, Lynn; Rao, Adupa P; D'Argenio, David Z; Beringer, Paul M

2018-06-18

Over the past decade, the prevalence of infections involving Methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) has increased significantly. Tedizolid (TZD) demonstrates excellent activity against MRSA and a favorable safety profile. The pharmacokinetics of several antibiotics has shown to be altered in CF patients. The purpose of this study was to characterize the pharmacokinetics of tedizolid in this population. Eleven patients with CF were randomized to receive tedizolid phosphate 200 mg PO or IV once daily for 3 doses, with minimum 2-day washout, followed by crossover to the remaining dosage form. Plasma and expectorated sputum were collected following the third dose of each dosage form for analysis. Population pharmacokinetics was performed using maximum-likelihood, expectation maximization method, and the disposition of TZD was described by a 2-compartment model. The sputum concentrations exceeded the unbound plasma concentrations with an estimated mean (%CV) sputum-to-unbound plasma penetration ratio of 2.88 (50.3). The estimated population mean ± standard deviation of total clearance, central volume of distribution, and bioavailability were 9.72 ± 1.62 L/h, 61.6 ± 6.94 L, and 1.04 ± 0.232 respectively. The total clearance is higher in CF patients when compared with healthy volunteers; however, it is similar to published data in patients with complicated skin and skin structure infections (cSSSI). This study demonstrates the oral bioavailability of tedizolid is excellent in patients with CF, and the plasma pharmacokinetics are similar to that reported for patients with cSSSI. Copyright © 2018 American Society for Microbiology.

Mechanisms and seasonal drivers of calcification in the temperate coral Turbinaria reniformis at its latitudinal limits.

PubMed

Ross, Claire L; Schoepf, Verena; DeCarlo, Thomas M; McCulloch, Malcolm T

2018-05-30

High-latitude coral reefs provide natural laboratories for investigating the mechanisms and limits of coral calcification. While the calcification processes of tropical corals have been studied intensively, little is known about how their temperate counterparts grow under much lower temperature and light conditions. Here, we report the results of a long-term (2-year) study of seasonal changes in calcification rates, photo-physiology and calcifying fluid (cf) chemistry (using boron isotope systematics and Raman spectroscopy) for the coral Turbinaria reniformis growing near its latitudinal limits (34.5° S) along the southern coast of Western Australia. In contrast with tropical corals, calcification rates were found to be threefold higher during winter (16 to 17° C) compared with summer (approx. 21° C), and negatively correlated with light, but lacking any correlation with temperature. These unexpected findings are attributed to a combination of higher chlorophyll a, and hence increased heterotrophy during winter compared with summer, together with the corals' ability to seasonally modulate pH cf , with carbonate ion concentration [Formula: see text] being the main controller of calcification rates. Conversely, calcium ion concentration [Ca 2+ ] cf declined with increasing calcification rates, resulting in aragonite saturation states Ω cf that were stable yet elevated fourfold above seawater values. Our results show that corals growing near their latitudinal limits exert strong physiological control over their cf in order to maintain year-round calcification rates that are insensitive to the unfavourable temperature regimes typical of high-latitude reefs. © 2018 The Author(s).

Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes.

PubMed

Ramos, M D; Trujillano, D; Olivar, R; Sotillo, F; Ossowski, S; Manzanares, J; Costa, J; Gartner, S; Oliva, C; Quintana, E; Gonzalez, M I; Vazquez, C; Estivill, X; Casals, T

2014-07-01

The term cystic fibrosis (CF)-like disease is used to describe patients with a borderline sweat test and suggestive CF clinical features but without two CFTR(cystic fibrosis transmembrane conductance regulator) mutations. We have performed the extensive molecular analysis of four candidate genes (SCNN1A, SCNN1B, SCNN1G and SERPINA1) in a cohort of 10 uncharacterized patients with CF and CF-like disease. We have used whole-exome sequencing to characterize mutations in the CFTR gene and these four candidate genes. CFTR molecular analysis allowed a complete characterization of three of four CF patients. Candidate variants in SCNN1A, SCNN1B, SCNN1G and SERPINA1 in six patients with CF-like phenotypes were confirmed by Sanger sequencing and were further supported by in silico predictive analysis, pedigree studies, sweat test in other family members, and analysis in CF patients and healthy subjects. Our results suggest that CF-like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low free drug concentration prevents inhibition of F508del CFTR functional expression by the potentiator VX-770 (ivacaftor).

PubMed

Matthes, Elizabeth; Goepp, Julie; Carlile, Graeme W; Luo, Yishan; Dejgaard, Kurt; Billet, Arnaud; Robert, Renaud; Thomas, David Y; Hanrahan, John W

2016-02-01

The most common cystic fibrosis (CF) mutation F508del inhibits the gating and surface expression of CFTR, a plasma membrane anion channel. Optimal pharmacotherapies will probably require both a 'potentiator' to increase channel open probability and a 'corrector' that improves folding and trafficking of the mutant protein and its stability at the cell surface. Interaction between CF drugs has been reported but remains poorly understood. CF bronchial epithelial cells were exposed to the corrector VX-809 (lumacaftor) and potentiator VX-770 (ivacaftor) individually or in combination. Functional expression of CFTR was assayed as the forskolin-stimulated short-circuit current (Isc ) across airway epithelial monolayers expressing F508del CFTR. The potentiated Isc response during forskolin stimulation was increased sixfold after pretreatment with VX-809 alone and reached ~11% that measured across non-CF monolayers. VX-770 (100 nM) and genistein (50 μM) caused similar levels of potentiation, which were not additive and were abolished by the CFTR inhibitor CFTRinh -172. The unbound fraction of VX-770 in plasma was 0.13 ± 0.04%, which together with previous measurements in patients given 250 mg p.o. twice daily, suggests a peak free plasma concentration of 1.5-8.5 nM. Chronic exposure to high VX-770 concentrations (>1 μM) inhibited functional correction by VX-809 but not in the presence of physiological protein levels (20-40 mg·mL(-1) ). Chronic exposure to a low concentration of VX-770 (100 nM) together with VX-809 (1 μM) also did not reduce the forskolin-stimulated Isc , relative to cells chronically exposed to VX-809 alone, provided it was assayed acutely using the same, clinically relevant concentration of potentiator. Chronic exposure to clinically relevant concentrations of VX-770 did not reduce F508del CFTR function. Therapeutic benefit of VX-770 + VX-809 (Orkambi) is probably limited by the efficacy of VX-809 rather than by inhibition by VX-770. © 2015 The British Pharmacological Society.

Trifluoroacetic Acid from Degradation of HCFCs and HFCs: A Three-dimensional Modeling Study

NASA Technical Reports Server (NTRS)

Kotamarthi, V. R.; Rodriguez, J. M.; Ko, M. K. W.; Tromp, T. K.; Sze, N. D.

1998-01-01

Trifluoroacetic acid (TFA; CF3 COOH) is produced by the degradation of the halocarbon replacements HFC-134a, HCFC-124, and HCFC-123. The formation of TFA occurs by HFC/HCFC reacting with OH to yield CF3COX (X = F or CI), followed by in-cloud hydrolysis of CF3COX to form TFA. The TFA formed in the clouds may be reevaporated but is finally deposited onto the surface by washout or dry deposition. Concern has been expressed about the possible long-term accumulation of TFA in certain aquatic environments, pointing to the need to obtain information on the concentrations of TFA in rainwater over scales ranging from local to continental. Based on projected concentrations for HFC-134a, HCFC-124, and HCFC-123 of 80, 10, and 1 pptv in the year 2010, mass conservation arguments imply an annually averaged global concentration of 0.16 microg/L if washout were the only removal mechanism for TFA. We present 3-D simulations of the HFC/HCFC precursors of TFA that include the rates of formation and deposition of TFA based on assumed future emissions. An established (GISS/Harvard/ UCI) but coarse-resolution (8 deg latitude by 10 deg longitude) chemical transport model was used. The anually averaged rainwater concentration of 0.12 gg/L (global) was calculated for the year 2010, when both washout and dry deposition are included as the loss mechanism for TFA from the atmosphere. For some large regions in midnorthern latitudes, values are larger, 0.15-0.20 microg/L. The highest monthly averaged rainwater concentrations of TFA for northern midlatitudes were calculated for the month of July, corresponding to 0.3-0.45 microg/L in parts of North America and Europe. Recent laboratory experiments have suggested that a substantial amount of vibrationally excited CF3CHFO is produced in the degradation of HFC-134a, decreasing the yield of TFA from this compound by 60%. This decrease would reduce the calculated amounts of TFA in rainwater in the year 2010 by 26%, for the same projected concentrations of precursors.

Trifluoroacetic Acid from Degradation of HCFCs and HFCs: A Three-Dimensional Modeling Study. Appendix P

NASA Technical Reports Server (NTRS)

Kotamarthi, V. R.; Rodriquez, J. M.; Ko, M. K. W.; Tromp, T. K.; Sze, N. D.; Prather, Michael J.

1998-01-01

Trifluoroacetic acid (TFA; CF3 COOH) is produced by the degradation of the halocarbon replacements HFC-134a, HCFC-124, and HCFC-123. The formation of TFA occurs by HFC/HCFC reacting with OH to yield CF3COX (X = F or CI), followed by in-cloud hydrolysis of CF to form TFA. The TFA formed in the clouds may be reevaporated but is finally deposited onto the surface by washout or dry deposition. Concern has been expressed about the possible long-term accumulation of TFA in certain aquatic environments, pointing to the need to obtain information on the concentrations of TFA in rainwater over scales ranging from local to continental. Based on projected concentrations for HFC-134a, HCFC-124, and HCFC-123 of 80, 10, and 1 pptv in the year 2010, mass conservation arguments imply an annually averaged global concentration of 0.16 micro g/L if washout were the only removal mechanism for TFA. We present 3-D simulations of the HFC/HCFC precursors of TFA that include the rates of formation and deposition of TFA based on assumed future emissions. An established (GISS[Harvard/ UCI) but coarse-resolution (8 deg latitude by 10 deg longitude) chemical transport model was used. The annually averaged rainwater concentration of 0.12 micro g/L (global) was calculated for the year 2010, when both washout and dry deposition are included as the loss mechanism for TFA from the atmosphere. For some large regions in midnorthern latitudes, values are larger. 0.15-0.20 micro g/L. The highest monthly averaged rainwater concentrations of TFA for northern midlatitudes were calculated for the month of July, corresponding to 0.3 - 0.45 micro g/L in parts of North America and Europe. Recent laboratory experiments have suggested that a substantial amount of vibrationally excited CF3CHFO is produced in the degradation of HFC-134a, decreasing the yield of TFA from this compound by 60%. This decrease would reduce the calculated amounts of TFA in rainwater in the year 2010 by 26%, for the same projected concentrations of precursors.

Trifluoroacetic Acid from Degradation of HCFCs and HFCs: A Three-Dimensional Modeling Study

NASA Technical Reports Server (NTRS)

Kotamarthi, V. R.; Rodriquez, J. M.; Ko, M. K. W.; Tromp, T. K.; Sze, N. D.

1998-01-01

Trifluoroacetic acid (TFA; CF3COOH) is produced by the degradation of the halocarbon replacements HFC-134a, HCFC-124, and HCFC-123. The formation of TFA occurs by HFC/HCFC reacting with OH to yield CF3COX (X = F or CI), followed by in-cloud hydrolysis of CF3COX to form TFA. The TFA formed in the clouds may be reevaporated but is finally deposited onto the surface by washout or dry deposition. Concern has been expressed about the possible long-term accumulation of TFA in certain aquatic environments, pointing to the need to obtain information on the concentrations of TFA in rainwater over scales ranging from local to continental. Based on projected concentrations for HFC-134a, HCFC-124, and HCFC-123 of 80, 10, and 1 pptv in the year 2010, mass conservation arguments imply an annually averaged global concentration of 0.16 micro g/L if washout were the only removal mechanism for TFA. We present 3-D simulations of the HFC/HCFC precursors of TFA that include the rates of formation and deposition of TFA based on assumed future emissions. An established (GISS/Harvard/ UCI) but coarse-resolution (8 deg latitude by 10 deg longitude) chemical transport model was used. The annually averaged rainwater concentration of 0.12 micro g/L (global) was calculated for the year 2010, when both washout and dry deposition are included as the loss mechanism for TFA from the atmosphere. For some large regions in midnorthern latitudes, values are larger, 0.15-0.20 micro g/L. The highest monthly averaged rainwater concentrations of TFA for northern midlatitudes were calculated for the month of July, corresponding to 0.3-0.45 micro g/L in parts of North America and Europe. Recent laboratory experiments have suggested that a substantial amount of vibrationally excited CF3CHFO is produced in the degradation of HFC-134a, decreasing the yield of TFA from this compound by 60%. This decrease would reduce the calculated amounts of TFA in rainwater in the year 2010 by 26%, for the same projected concentrations of precursors.

Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant patients.

PubMed

Berge, M; Guillemain, R; Boussaud, V; Pham, M-H; Chevalier, P; Batisse, A; Amrein, C; Dannaoui, E; Loriot, M-A; Lillo-Le Louet, A; Billaud, E M

2009-06-01

Aspergillosis is a high-risk complication in cystic fibrosis (CF) lung transplant patients. Azole antifungal drugs inhibit CYP3A4, resulting in significant metabolic drug-drug interactions. Voriconazole (VRZ) was marketed without therapeutic drug monitoring (TDM) recommendations, consistent with favorable pharmacokinetics, but regular determinations of plasma VRZ concentration were introduced in our center to manage interactions with calcineurin inhibitors and to document the achievement of therapeutic levels. VRZ TDM data analysis for trough concentration (C0) and peak concentration (C2) was carried out, using validated liquid chromatography assay with ultraviolet detection, for 35 CF lung transplant patients (mean age 25 years, mean weight 47 kg, balanced sex ratio) since 2003. Therapeutic range (C0: 1.5 +/- 0.5 - C2 : 4.0 +/- 1.0 mg/L) was expressed relative to pivotal pharmacokinetic trial data. The duration of VRZ treatment ranged from 9 days to 22 months. The recommended standard dose of VRZ (200 mg twice a day, following the loading dose) resulted in significant plasma concentrations (>0.5 mg/L) in 20% of CF lung transplant patients. Therapeutic concentrations were obtained using higher doses (average 570 +/- 160 mg/day, +43%, P<0.01). Despite adaptation, C0 remained <0.5 mg/L (11%), even when the drug was administered intravenously, highlighting the variability of VRZ pharmacokinetics, possibly enhanced by CYP2C19 polymorphism. The risk of inefficacy during periods of underdosage was overcome by treatment with antifungal drug combinations (caspofungin, n=10). The therapeutic index was limited by neurologic effects (14%) and hepatic abnormalities (30%). VRZ concentrations correlated significantly (P<0.01) with aspartate aminotransferase levels but not with bilirubin levels. VRZ acted as a metabolic inhibitor of tacrolimus (C0 to dose ratio 5.8 +/- 2.6, n=31/VRZ versus 1.7 +/- 0.9 alone, P<0.001). Large changes in azole concentration affected the magnitude of the drug-drug interactions and adjustment requirements. TDM is required because VRZ levels are often undetectable in treated CF lung transplant patients, supporting the use of antifungal drug combinations until achievement of VRZ C0 at a steady state between 1 and 2 mg/L. Plasma VRZ concentrations should be determined for the quantitative, individualized management of drug-drug interactions in lung transplant patients, in particular immunosuppressant such as tacrolimus, considering VRZ to be both a target and an inhibitor of CYP3A4.

The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats.

PubMed

Ochaion, A; Bar-Yehuda, S; Cohen, S; Amital, H; Jacobson, K A; Joshi, B V; Gao, Z G; Barer, F; Patoka, R; Del Valle, L; Perez-Liz, G; Fishman, P

2008-08-15

The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant- and collagen-induced arthritis. In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappaB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant-induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 microg/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), IkappaB kinase (IKK), I kappa B (IkappaB), NF-kappaB and tumor necrosis factor-alpha (TNF-alpha) took place. In addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappaB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A(3)AR agonists for the treatment of rheumatoid arthritis.

Influence of SNPs in Genes that Modulate Lung Disease Severity in a Group of Mexican Patients with Cystic Fibrosis.

PubMed

Yokoyama, Emiy; Chávez-Saldaña, Margarita; Orozco, Lorena; Cuevas, Francisco; Lezana, José Luis; Vigueras-Villaseñor, Rosa María; Rojas-Castañeda, Julio Cesar; Landero, Daniel Adrian

2018-04-24

The variation in cystic fibrosis (CF) lung disease not always is explained by the CFTR genotype, so it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of CF, so we investigated the association of allelic variants in modifier genes that modulate the severity of lung function in a group of Mexican patients diagnosed with CF. We included 140 CF patients classified according to lung phenotype and analyzed 17 single nucleotide polymorphisms (SNPs) by TaqMan ® allelic discrimination. We demonstrated that patients with GG or GC genotype of the allelic variant rs11003125 (MBL2-550) of the MBL2 gene exhibit most of the lung manifestations at an earlier age; and the rs1042713 allelic variant of ADRB2 gene, showed statistical difference only with the age of first spirometry. When we used the dominant model, the MBL2 allele rs11003125 (MBL2-550; p = 0.022, Odds Ratio (OR) 2.87, 95% CI 1.14-7.27) was significantly associated with CF patients as risk factor, and the ADRB2 allele rs1042713 (p.Arg16Gly; p = 0.005, Odds Ratio (OR) 0.37, 95% CI 0.19-0.75) was significantly associated with CF patients as protect factor. Our findings suggest that the MBL2 and ADRB2 genes exerts an important genetic influence on the lung disease in our patients. Taking into account our results, we insist on not leaving aside this type of studies, since having techniques such as GWAS or WES will be able to advance in achieving a better quality of life for CF patients with severe lung disease. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Alpha-1 Antitrypsin Mitigates the Inhibition of Airway Epithelial Cell Repair by Neutrophil Elastase.

PubMed

Garratt, Luke W; Sutanto, Erika N; Ling, Kak-Ming; Looi, Kevin; Iosifidis, Thomas; Martinovich, Kelly M; Shaw, Nicole C; Buckley, Alysia G; Kicic-Starcevich, Elizabeth; Lannigan, Francis J; Knight, Darryl A; Stick, Stephen M; Kicic, Anthony

2016-03-01

Neutrophil elastase (NE) activity is associated with many destructive lung diseases and is a predictor for structural lung damage in early cystic fibrosis (CF), which suggests normal maintenance of airway epithelium is prevented by uninhibited NE. However, limited data exist on how the NE activity in airways of very young children with CF affects function of the epithelia. The aim of this study was to determine if NE activity could inhibit epithelial homeostasis and repair and whether any functional effect was reversible by antiprotease alpha-1 antitrypsin (α1AT) treatment. Viability, inflammation, apoptosis, and proliferation were assessed in healthy non-CF and CF pediatric primary airway epithelial cells (pAECnon-CF and pAECCF, respectively) during exposure to physiologically relevant NE. The effect of NE activity on pAECCF wound repair was also assessed. We report that viability after 48 hours was significantly decreased by 100 nM NE in pAECnon-CF and pAECCF owing to rapid cellular detachment that was accompanied by inflammatory cytokine release. Furthermore, both phenotypes initiated an apoptotic response to 100 nM NE, whereas ≥ 50 nM NE activity significantly inhibited the proliferative capacity of cultures. Similar concentrations of NE also significantly inhibited wound repair of pAECCF, but this effect was reversed by the addition of α1AT. Collectively, our results demonstrate free NE activity is deleterious for epithelial homeostasis and support the hypothesis that proteases in the airway contribute directly to CF structural lung disease. Our results also highlight the need to investigate antiprotease therapies in early CF disease in more detail.

Comparison of Carotid-Femoral and Brachial-Ankle Pulse-Wave Velocity in Association With Target Organ Damage in the Community-Dwelling Elderly Chinese: The Northern Shanghai Study.

PubMed

Lu, Yuyan; Zhu, Mengyun; Bai, Bin; Chi, Chen; Yu, Shikai; Teliewubai, Jiadela; Xu, Henry; Wang, Kai; Xiong, Jing; Zhou, Yiwu; Ji, Hongwei; Fan, Ximin; Yu, Xuejing; Li, Jue; Blacher, Jacques; Zhang, Yi; Xu, Yawei

2017-02-20

Carotid-femoral pulse-wave velocity (cf-PWV) and brachial-ankle PWV (ba-PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf-PWV and ba-PWV. A total of 1599 community-dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf-PWV and ba-PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima-media thickness, arterial plaque, creatinine clearance rate, and urinary albumin-creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba-PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf-PWV and ba-PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf-PWV, but not ba-PWV, was significantly associated with carotid intima-media thickness and creatinine clearance rate ( P <0.05). When cf-PWV and ba-PWV were both or separately put into the same full-mode model after adjustment for confounders, only cf-PWV, but not ba-PWV, showed significant association with carotid intima-media thickness and creatinine clearance rate ( P <0.05). Similar results were observed in logistic regression analysis. Taken together, in the community-dwelling elderly Chinese, cf-PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba-PWV. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Correlation of cell-free DNA plasma concentration with severity of non-alcoholic fatty liver disease.

PubMed

Karlas, Thomas; Weise, Lara; Kuhn, Stephanie; Krenzien, Felix; Mehdorn, Matthias; Petroff, David; Linder, Nicolas; Schaudinn, Alexander; Busse, Harald; Keim, Volker; Pratschke, Johann; Wiegand, Johannes; Splith, Katrin; Schmelzle, Moritz

2017-05-19

The assessment of fibrosis and inflammatory activity is essential to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk for progressive disease. Serum markers and ultrasound-based methods can replace liver biopsy for fibrosis staging, whereas non-invasive characterization of inflammatory activity remains a clinical challenge. Cell-free DNA (cfDNA) is a novel non-invasive biomarker for assessing cellular inflammation and cell death, which has not been evaluated in NAFLD. Patients and healthy controls from two previous studies were included. NAFLD disease activity and severity were non-invasively characterized by liver stiffness measurement (transient elastography, TE) including steatosis assessment with controlled attenuation parameter (CAP), single-proton magnetic resonance spectroscopy ( 1 H-MRS) for determination of hepatic fat fraction, aminotransferases and serum ferritin. cfDNA levels (90 and 222 bp fragments) were analyzed using quantitative real-time PCR. Fifty-eight NAFLD patients (age 62 ± 11 years, BMI 28.2 ± 3.5 kg/m 2 ) and 13 healthy controls (age 38 ± 12 years, BMI 22.4 ± 2.1 kg/m 2 ) were included. 90 bp cfDNA levels were significantly higher in NAFLD patients compared to healthy controls: 3.7 (1.3-23.1) vs. 2.9 (1.4-4.1) ng/mL (p = 0.014). In the NAFLD cohort, circulating cfDNA correlated significantly with disease activity and severity, especially in patients with elevated liver stiffness (n = 13, 22%) compared to cases with TE values ≤7 kPa: cf90 bp 6.05 (2.41-23.13) vs. 3.16 (1.29-7.31) ng/mL (p < 0.001), and cf222 bp 14.41 (9.27-22.90) vs. 11.32 (6.05-18.28) ng/mL (p = 0.0041). Cell-free DNA plasma concentration correlates with established non-invasive markers of NAFLD activity and severity. Therefore, cfDNA should be further evaluated as biomarker for identifying patients at risk for progressive NAFLD.

New approach for cystic fibrosis diagnosis based on chloride/potassium ratio analyzed in non-invasively obtained skin-wipe sweat samples by capillary electrophoresis with contactless conductometric detection.

PubMed

Ďurč, Pavol; Foret, František; Pokojová, Eva; Homola, Lukáš; Skřičková, Jana; Herout, Vladimír; Dastych, Milan; Vinohradská, Hana; Kubáň, Petr

2017-05-01

A new approach for sweat analysis used in cystic fibrosis (CF) diagnosis is proposed. It consists of a noninvasive skin-wipe sampling followed by analysis of target ions using capillary electrophoresis with contactless conductometric detection (C4D). The skin-wipe sampling consists of wiping a defined skin area with precleaned cotton swab moistened with 100 μL deionized water. The skin-wipe sample is then extracted for 3 min into 400 μL deionized water, and the extract is analyzed directly. The developed sampling method is cheap, simple, fast, and painless, and can replace the conventional pilocarpine-induced sweat chloride test commonly applied in CF diagnosis. The aqueous extract of the skin-wipe sample content is analyzed simultaneously by capillary electrophoresis with contactless conductometric detection using a double opposite end injection. A 20 mmol/L L-histidine/2-(N-morpholino)ethanesulfonic acid and 2 mmol/L 18-crown-6 at pH 6 electrolyte can separate all the major ions in less than 7 min. Skin-wipe sample extracts from 30 study participants-ten adult patients with CF (25-50 years old), ten pediatric patients with CF (1-15 years old), and ten healthy control individuals (1-18 years old)-were obtained and analyzed. From the analyzed ions in all samples, a significant difference between chloride and potassium concentrations was found in the CF patients and healthy controls. We propose the use of the Cl - /K + ratio rather than the absolute Cl - concentration and a cutoff value of 4 in skin-wipe sample extracts as an alternative to the conventional sweat chloride analysis. The proposed Cl - /K + ion ratio proved to be a more reliable indicator, is independent of the patient's age, and allows better differentiation between non-CF individuals and CF patients having intermediate values on the Cl - sweat test. Figure New approach for cystic fibrosis diagnosis based on skin-wipe sampling of forearm and analysis of ionic content (Cl - /K + ratio) in skin-wipe extracts by capillary electrophoresis with contactless conductometric detection.

CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.

PubMed

Bonadia, Luciana Cardoso; de Lima Marson, Fernando Augusto; Ribeiro, Jose Dirceu; Paschoal, Ilma Aparecida; Pereira, Monica Corso; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia

2014-05-01

There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF-related diabetes (p=0.040), chloride concentration in the sweat test (p=0.040) and chronic infection by microorganisms (Staphylococcus aureus - p=0.039; mucoid P. aeruginosa - p=0.001). There is no positive association with the status of other clinical markers and the CFTR genotype groups. For clinical association with pancreatic insufficiency (as clinical marker for digestive symptoms), no association was related. The adults with CF diagnosed by sweat test have specific clinical and genotypic characteristics, being a population that should be studied to cause better future management. Some patients treated as CF disease by clinical symptoms, showed no disease, taking into account the sweat test and complete exon sequencing/MLPA screening. Copyright © 2014. Published by Elsevier B.V.

Increased capillary permeability mediated by a dengue virus-induced lymphokine.

PubMed Central

Khanna, M; Chaturvedi, U C; Sharma, M C; Pandey, V C; Mathur, A

1990-01-01

The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine. PMID:2312168

Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas.

PubMed

Brennan, Marie-Luise; Schrijver, Iris

2016-01-01

Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

PubMed

Bos, Aukje C; Passé, Kimberly M; Mouton, Johan W; Janssens, Hettie M; Tiddens, Harm A W M

2017-01-01

Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree. To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF. Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included. 35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics. After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Neck circumference and early stage atherosclerosis: the cardiometabolic risk in Chinese (CRC) study.

PubMed

Liang, Jun; Wang, Yu; Li, Hongyan; Liu, Xuekui; Qiu, Qinqin; Qi, Lu

2014-07-08

Neck circumference (NC) has been previously related to cardiometabolic risk factors. In this study we examined the association between NC and early stage atherosclerosis in Chinese adults. The study samples were from a community-based health examination survey in central China. In total 2,318 men and women (18-64 y) were included in the final analyses. Carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and NC were measured. After adjustment for age, sex, lipids, glucose, blood pressure, heart rate, body mass index (BMI), high NC was significantly associated with an increasing trend of cfPWV, cdPWV and crPWV (P = 0.001, 0.049, and 0.038; respectively). In addition, we found significant interaction between hypertension status and NC level in relation to cfPWV, adjusted for age, sex, BMI, fasting glucose, lipids and heart rate(P for interaction = 0.034). The associations between NC and cfPWV were significant (P = 0.02) among those with hypertension, but not significant among those without hypertension. Our data showed that high NC was associated with an increased risk of early stage atherosclerosis in Chinese adults, independent of other metabolic risk factors. Hypertension might modify the association between NC and cfPWV.

Enhanced linear-array photoacoustic beamforming using modified coherence factor.

PubMed

Mozaffarzadeh, Moein; Yan, Yan; Mehrmohammadi, Mohammad; Makkiabadi, Bahador

2018-02-01

Photoacoustic imaging (PAI) is a promising medical imaging modality providing the spatial resolution of ultrasound imaging and the contrast of optical imaging. For linear-array PAI, a beamformer can be used as the reconstruction algorithm. Delay-and-sum (DAS) is the most prevalent beamforming algorithm in PAI. However, using DAS beamformer leads to low-resolution images as well as high sidelobes due to nondesired contribution of off-axis signals. Coherence factor (CF) is a weighting method in which each pixel of the reconstructed image is weighted, based on the spatial spectrum of the aperture, to mainly improve the contrast. We demonstrate that the numerator of the formula of CF contains a DAS algebra and propose the use of a delay-multiply-and-sum beamformer instead of the available DAS on the numerator. The proposed weighting technique, modified CF (MCF), has been evaluated numerically and experimentally compared to CF. It was shown that MCF leads to lower sidelobes and better detectable targets. The quantitative results of the experiment (using wire targets) show that MCF leads to for about 45% and 40% improvement, in comparison with CF, in the terms of signal-to-noise ratio and full-width-half-maximum, respectively. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment.

PubMed

Bar-Yehuda, S; Rath-Wolfson, L; Del Valle, L; Ochaion, A; Cohen, S; Patoka, R; Zozulya, G; Barer, F; Atar, E; Piña-Oviedo, S; Perez-Liz, G; Castel, D; Fishman, P

2009-10-01

Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A(3) adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 microg/kg given twice daily) was initiated. The A(3) adenosine receptor antagonist MRS1220 (100 microg/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-kappaB signaling pathway, resulting in down-regulation of tumor necrosis factor alpha. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. CF101 deregulated the NF-kappaB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.

Cladosporium fulvum CfHNNI1 induces hypersensitive necrosis, defence gene expression and disease resistance in both host and nonhost plants.

PubMed

Cai, Xin-Zhong; Zhou, Xin; Xu, You-Ping; Joosten, Matthieu H A J; de Wit, Pierre J G M

2007-05-01

Nonhost resistance as a durable and broad-spectrum defence strategy is of great potential for agricultural applications. We have previously isolated a cDNA showing homology with genes encoding bZIP transcription factors from tomato leaf mould pathogen Cladosporium fulvum. Upon expression, the cDNA results in necrosis in C. fulvum host tomato and nonhost tobacco plants and is thus named CfHNNI1 (for C . f ulvum host and nonhost plant necrosis inducer 1). In the present study we report the induction of necrosis in a variety of nonhost plant species belonging to three families by the transient in planta expression of CfHNNI1 using virus-based vectors. Additionally, transient expression of CfHNNI1 also induced expression of the HR marker gene LeHSR203 and greatly reduced the accumulation of recombinant Potato virus X. Stable CfHNNI1 transgenic tobacco plants were generated in which the expression of CfHNNI1 is under the control of the pathogen-inducible hsr203J promoter. When infected with the oomycetes pathogen Phytophthora parasitica var. nicotianae, these transgenic plants manifested enhanced expression of CfHNNI1 and subsequent accumulation of CfHNNI1 protein, resulting in high expression of the HSR203J and PR genes, and strong resistance to the pathogen. The CfHNNI1 transgenic plants also exhibited induced resistance to Pseudomonas syringae pv. tabaci and Tobacco mosaic virus. Furthermore, CfHNNI1 was highly expressed and the protein was translocated into plant cells during the incompatible interactions between C. fulvum and host and nonhost plants. Our results demonstrate that CfHNNI1 is a potential general elicitor of hypersensitive response and nonhost resistance.

Liposome-chaperoned cell-free synthesis for the design of proteoliposomes: Implications for therapeutic delivery.

PubMed

Lu, Mei; Zhao, Xiaoyun; Xing, Haonan; Xun, Zhe; Yang, Tianzhi; Cai, Cuifang; Wang, Dongkai; Ding, Pingtian

2018-04-03

Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application. The incorporation of functional membrane proteins (MPs) or peptides allows the transfer of biological properties to liposomes and imparts them with improved circulation, increased targeting, and efficient intracellular delivery. Liposome-chaperoned CF synthesis enables production of proteoliposomes in one-step reaction, which not only substantially simplifies the production procedure but also keeps protein functionality intact. Building off these observations, proteoliposomes with integrated MPs represent an excellent candidate for therapeutic delivery. In this review, we describe recent advances in CF synthesis with emphasis on detailing key factors for improving CF expression efficiency. Furthermore, we provide insights into strategies for rational design of proteoliposomal nanodelivery systems via CF synthesis. Liposome-chaperoned CF synthesis has emerged as a powerful approach for the design of recombinant proteoliposomes in one-step reaction. The incorporation of bioactive MPs or peptides into liposomes via CF synthesis can facilitate the development of proteoliposomal nanodelivery systems with improved circulation, increased targeting, and enhanced cellular delivery capacity. Moreover, by adapting lessons learned from natural delivery vehicles, novel bio-inspired proteoliposomes with enhanced delivery properties could be produced in CF systems. In this review, we first give an overview of CF synthesis with focus on enhancing protein expression in liposome-chaperoned CF systems. Furthermore, we intend to provide insight into harnessing CF-synthesized proteoliposomes for efficient therapeutic delivery. Copyright © 2018. Published by Elsevier Ltd.

The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport

PubMed Central

2017-01-01

The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs. However, it provides ambiguous results for intermediate sweat chloride cases while not reflecting disease progression when classifying the complex CF disease spectrum given the pleiotropic effects of gene modifiers and environment. Herein we report the first characterization of the sweat metabolome from screen-positive CF infants and identify metabolites associated with disease status that complement sweat chloride testing. Pilocarpine-stimulated sweat specimens were collected independently from two CF clinics, including 50 unaffected infants (e.g., carriers) and 18 confirmed CF cases. Nontargeted metabolite profiling was performed using multisegment injection–capillary electrophoresis–mass spectrometry as a high throughput platform for analysis of polar/ionic metabolites in volume-restricted sweat samples. Amino acids, organic acids, amino acid derivatives, dipeptides, purine derivatives, and unknown exogenous compounds were identified in sweat when using high resolution tandem mass spectrometry, including metabolites associated with affected yet asymptomatic CF infants, such as asparagine and glutamine. Unexpectedly, a metabolite of pilocarpine, used to stimulate sweat secretion, pilocarpic acid, and a plasticizer metabolite from environmental exposure, mono(2-ethylhexyl)phthalic acid, were secreted in the sweat of CF infants at significantly lower concentrations relative to unaffected CF screen-positive controls. These results indicated a deficiency in human paraoxonase, an enzyme unrelated to mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) and impaired chloride transport, which is a nonspecific arylesterase/lactonase known to mediate inflammation, bacterial biofilm formation, and recurrent lung infections in affected CF children later in life. This work sheds new light into the underlying mechanisms of CF pathophysiology as required for new advances in precision medicine of orphan diseases that benefit from early detection and intervention, including new molecular targets for therapeutic intervention. PMID:28852705

The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport.

PubMed

Macedo, Adriana N; Mathiaparanam, Stellena; Brick, Lauren; Keenan, Katherine; Gonska, Tanja; Pedder, Linda; Hill, Stephen; Britz-McKibbin, Philip

2017-08-23

The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs. However, it provides ambiguous results for intermediate sweat chloride cases while not reflecting disease progression when classifying the complex CF disease spectrum given the pleiotropic effects of gene modifiers and environment. Herein we report the first characterization of the sweat metabolome from screen-positive CF infants and identify metabolites associated with disease status that complement sweat chloride testing. Pilocarpine-stimulated sweat specimens were collected independently from two CF clinics, including 50 unaffected infants (e.g., carriers) and 18 confirmed CF cases. Nontargeted metabolite profiling was performed using multisegment injection-capillary electrophoresis-mass spectrometry as a high throughput platform for analysis of polar/ionic metabolites in volume-restricted sweat samples. Amino acids, organic acids, amino acid derivatives, dipeptides, purine derivatives, and unknown exogenous compounds were identified in sweat when using high resolution tandem mass spectrometry, including metabolites associated with affected yet asymptomatic CF infants, such as asparagine and glutamine. Unexpectedly, a metabolite of pilocarpine, used to stimulate sweat secretion, pilocarpic acid, and a plasticizer metabolite from environmental exposure, mono(2-ethylhexyl)phthalic acid, were secreted in the sweat of CF infants at significantly lower concentrations relative to unaffected CF screen-positive controls. These results indicated a deficiency in human paraoxonase, an enzyme unrelated to mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) and impaired chloride transport, which is a nonspecific arylesterase/lactonase known to mediate inflammation, bacterial biofilm formation, and recurrent lung infections in affected CF children later in life. This work sheds new light into the underlying mechanisms of CF pathophysiology as required for new advances in precision medicine of orphan diseases that benefit from early detection and intervention, including new molecular targets for therapeutic intervention.

Test-Retest Variability in Lesion SUV and Lesion SUR in 18F-FDG PET: An Analysis of Data from Two Prospective Multicenter Trials.

PubMed

Hofheinz, Frank; Apostolova, Ivayla; Oehme, Liane; Kotzerke, Jörg; van den Hoff, Jörg

2017-11-01

Quantitative assessment of radio- and chemotherapy response with 18 F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test-retest stability, thus becomes crucial. However, a recent study demonstrated substantial test-retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non-small cell lung cancer from the prospective multicenter trials ACRIN 6678 ( n = 34) and MK-0646-008 ( n = 39) were included in this study. All patients underwent two 18 F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1-7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUV max and SUV peak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time-corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering R TRV (TRV SUR /TRV SUV ), a ratio reflecting the reduction in the TRV in SUR relative to SUV. R TRV was correlated with the group-averaged-value difference (δ) in CF mean (δCF mean ) of the quantity δCF = |CF - 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value δCF min and computing δCF mean and R TRV for the remaining subgroup of patients/lesions with δCF ≥ δCF min Results: The group-averaged TRV SUV and TRV SUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an R TRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small δCF values in the investigated prospective study groups. In fact, subgroup analysis with increasing δCF min thresholds revealed a pronounced negative correlation (Spearman ρ = -0.99, P < 0.001) between R TRV and δCF mean , where R TRV ≈ 0.4 in the δCF min = 20% subgroup, corresponding to a more than 2-fold reduction of TRV SUR compared with TRV SUV Conclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

PubMed Central

Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

2013-01-01

Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment. PMID:23698746

Enhanced IL-1{beta}-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both mitogen-activated protein kinases and NF-{kappa}B signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muselet-Charlier, Celine; Universite Pierre et Marie Curie-Paris 6, Paris, UMR-S719, F-75012; Roque, Telma

2007-06-01

Transcription nuclear factor-{kappa}B (NF-{kappa}B) is hyperactivated in cystic fibrosis (CF) lung epithelial cells, and participates in exaggerated IL-8 production in the CF lung. We recently found that rapid activation of NF-{kappa}B occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1{beta} stimulation, which was not observed in its CFTR-corrected lung epithelial S9 cell line (corrected cells). To test whether other signaling pathways such as that of mitogen-activated protein kinases (MAPKs) could be involved in IL-1{beta}-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-{kappa}B. Within 30 min, exposure to IL-1{beta} causedmore » high activation of NF-{kappa}B, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1{beta}-stimulated CF cells with a series of chemical inhibitors of NF-{kappa}B, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1{beta}-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-{kappa}B and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF.« less

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors.

PubMed

Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik; Thronicke, Anja; Tintelnot, Kathrin

2017-01-01

An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Clinical, microbiological and laboratory data of 161 patients aged 6-59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13-32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955-0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009-0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873-98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518-93.0705, p<0.05). Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

PubMed Central

Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik

2017-01-01

Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp. PMID:28178337

Epigenetic markers in circulating cell-free DNA as prognostic markers for survival of castration-resistant prostate cancer patients.

PubMed

Hendriks, Rianne J; Dijkstra, Siebren; Smit, Frank P; Vandersmissen, Johan; Van de Voorde, Hendrik; Mulders, Peter F A; van Oort, Inge M; Van Criekinge, Wim; Schalken, Jack A

2018-04-01

Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. In this prospective study, patients were included before starting new treatment after developing CRPC. The blood samples were collected prior to start of the treatment and at three time points thereafter. cfDNA was extracted from 1.5 mL of plasma and before performing a methylation-specific PCR, bisulfate modification was carried out. The median levels of cfDNA, GSTP1, and APC copies in the baseline samples of CRPC patients (n = 47) were higher than in controls (n = 30). In the survival analysis, the group with baseline marker levels below median had significant less PCa-related deaths (P-values <0.02) and did not reach the median survival point. The survival distributions for the groups were statistically significant for the cfDNA concentration, GSTP1 and APC copies, as well as PSA combined with GSTP1 + APC (P-values <0.03). Furthermore, there were strong positive correlations between PSA and marker response after starting treatment (P-values <0.04). In conclusion, this study showed the kinetics of methylated cfDNA (GSTP1 and APC) in plasma of CRPC patients after starting treatment. Furthermore, the value of the markers before treatment is prognostic for overall survival. These results are promising for developing a test to guide treatment-decision-making for CRPC patients. © 2018 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Effects of Frequency Spreads on Beam Breakup Instabilities in Linear Accelerators

DTIC Science & Technology

1989-05-11

i - 1)A/(N - 1), i = 1, ....N. In keeping with the above model [ cf . Eq. (4)], we assume that there is an equal probability (1/N) for each of these...solution (5), which contains two approximations to (10) and (11) [ cf ., N 4 - limit, and then asymptotic analysis], could accurately model the numerical...that the transition time Tl = 0(1) is the time when the phase mixing factor A0 t is roughly balanced by the BBU exponentiation factoro 1.64W I / 3 [ cf

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Elisa K.; Woods, Ryan; McBride, Mary L.

Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiacmore » risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.« less

Chemical composition of scales generated from oil industry and correlation to radionuclide contents and gamma-ray measurements of (210)Pb.

PubMed

Al Attar, Lina; Safia, Bassam; Abdul Ghani, Basem

2016-03-01

Scale generated from the maintenance of equipment contaminated by naturally occurring radioactive materials may contain also chemical components that cause hazardous pollution to human health and the environment. This study spotlights the characterisation of chemical pollutants in scales in relation to home-made comparison samples as no reference material for such waste exists. Analysis by energy dispersive x-ray fluorescence, with accuracy and precision better than 90%, revealed that barium was the most abundant element in scale samples, ranging from 1.4 to 38.2%. The concentrations of the toxic elements such as lead and chromium were as high as 2.5 and 1.2% respectively. Statistically, high correlation was observed between the concentration of Ba and Sr, sample density, radionuclide contents ((210)Pb and (226)Ra) and self-attenuation factor used for the radio-measurements. However, iron showed a reverse correlation. Interpretation of data with regards to the mineralogical components indicated that (226)Ra and (210)Pb co-precipitated with the insoluble salt Ba0.75Sr0.25SO4. Since both Ba and Sr have high Z, samples of high density (ρ) were accompanied with high values of self-attenuation correction factors (Cf) for the emitted radiation; correlation matrix of Pearson reached 0.935 between ρ and Cf. An attempt to eliminate the effect of the elemental composition and improve gamma measurements of (210)Pb activity concentration in scale samples was made, which showed no correction for self-attenuation was needed when sample densities were in the range 1.0-1.4 g cm(-3). For denser samples, a mathematical model was developed. Accurate determinations of radionuclide and chemical contents of scale would facilitate future Environmental Impact Assessment for the petroleum industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distribution and environmental assessment of trace elements contamination of water, sediments and flora from Douro River estuary, Portugal.

PubMed

Ribeiro, C; Couto, C; Ribeiro, A R; Maia, A S; Santos, M; Tiritan, M E; Pinto, E; Almeida, A A

2018-10-15

The present study evaluated the content and distribution of several trace elements (Li, Be, Al, V, Cr, Co, Ni, Cu, Zn, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, and U) in the Douro River estuary. For that, three matrices were collected (water, sediments and native local flora) to assess the extent of contamination by these elements in this estuarine ecosystem. Results showed their occurrence in estuarine water and sediments, but significant differences were recorded on the concentration levels and pattern of distribution among both matrices and sampling points. Generally, the levels of trace elements were higher in the sediments than in the respective estuarine water. Nonetheless, no correlation among trace elements was determined between water and sediments, except for Cd. Al was the trace element found at highest concentration at both sediments and water followed by Zn. Pollution indices such as geo-accumulation (I geo ), enrichment factor (EF) and contamination factor (CF) were determined to understand the levels and sources of trace elements pollution. I geo showed strong contamination by anthropogenic activities for Li, Al, V, Cr, Ni, Cu, Zn, Ba and Pb at all sampling points while EF and CF demonstrated severe enrichment and contamination by Se, Sb and Pb. Levels of trace elements were compared to acceptable values for aquatic organisms and Sediment Quality Guidelines. The concentration of some trace elements, namely Al, Pb and Cu, were higher than those considered acceptable, with potential negative impact on local living organisms. Nevertheless, permissible values for all trace elements are still not available, demonstrating that further studies are needed in order to have a complete assessment of environmental risk. Furthermore, the occurrence and possible accumulation of trace elements by local plant species and macroalgae were investigated as well as their potential use as bioindicators of local pollution and for phytoremediation purposes. Copyright © 2018 Elsevier B.V. All rights reserved.

EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6

PubMed Central

Wu, Yi-Long; Sequist, Lecia V; Hu, Cheng-Ping; Feng, Jifeng; Lu, Shun; Huang, Yunchao; Li, Wei; Hou, Mei; Schuler, Martin; Mok, Tony; Yamamoto, Nobuyuki; O'Byrne, Kenneth; Hirsh, Vera; Gibson, Neil; Massey, Dan; Kim, Miyoung; Yang, James Chih-Hsin

2017-01-01

Background: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). Methods: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit. Results: EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P<0.0001) and cfDNA− (LL3: HR, 0.46; P<0.0001; LL6: HR, 0.12; P<0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients. Conclusions: Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status. PMID:28006816

Neonatal injury at cephalic vaginal delivery: a retrospective analysis of extent of association with shoulder dystocia.

PubMed

Iskender, Cantekin; Kaymak, Oktay; Erkenekli, Kudret; Ustunyurt, Emin; Uygur, Dilek; Yakut, Halil Ibrahim; Danisman, Nuri

2014-01-01

To describe the risk factors and labor characteristics of Clavicular fracture (CF) and brachial plexus injury (BPI); and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300) was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2%) sustained permanent injury, whereas one neonate (4.5%) with BPI following shoulder dystocia sustained permanent injury (p = 0.34). BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae.

Learners' Perception of Corrective Feedback in Pair Work

ERIC Educational Resources Information Center

Yoshida, Reiko

2008-01-01

The present study examines Japanese language learners' perception of corrective feedback (CF) in pair work in relation to their noticing and understanding of their partners' CF and the factors that influence it. This study focuses on three learners, who worked together in pair work. The data collection methods consist of classroom observation,…

Simultaneous anaerobic transformation of carbon tetrachloride to carbon dioxide and tetrachloroethene to ethene in a continuous flow column.

PubMed

Azizian, Mohammad F; Semprini, Lewis

2017-08-01

The simultaneous anaerobic transformation of tetrachloroethene (PCE) and carbon tetrachloride (CT) was evaluated in a continuous flow column. The column was packed with quartz sand and bioaugmented with the Evanite culture (EV) that is capable of transforming PCE to ethene. Azizian and Semprini (2016) reported that PCE and CT could be simultaneously transformed in the column, with PCE (0.1mM) transformed mainly to ethene and CT (0.015mM) to chloroform (CF) (20%) and an unknown transformation product, likely carbon dioxide (CO 2 ). The fermentation of propionate, formed from lactate fermentation, was inhibited after the transformation of CT, likely from the exposure to CF. Reported here is the second phase of that study where a second bioaugmentation of the EV culture was made to reintroduce a lactate and propionate fermenting population to the column. Effective lactate and propionate fermentation were restored with a H 2 concentration of ~25nM maintained in the column effluent. PCE (0.1mM) was effectively transformed to ethene (~98%) and vinyl chloride (VC) (~2%). Unlabeled CT (0.015 to 0.03mM) was completely transformed with a transient build-up of CF and chloromethane (CM), which were subsequently removed below their detection limits. A series of transient tests were initiated through the addition of carbon-13 labeled CT ( 13 CT), with concentrations gradually increased from 0.03 to 0.10mM. GC-MS analysis of the column effluent showed that 13 C labeled CO 2 ( 13 CO 2 ) was formed, ranging from 82 to 93% of the 13 CT transformed, with the transient increases in 13 CO 2 associated with the increased concentration of 13 CT. A modified COD analysis indicated a lesser amount of 13 CT (18%) was transformed to soluble products, while 13 CO 2 represented 82% the 13 CT transformed. In a final transient test, the influent lactate concentration was decreased from 1.1 to 0.67mM. The transformation of both CT and PCE changed dramatically. Only 59% of the 13 CT was transformed, primarily to CF. 13 CO 2 concentrations gradually decreased to background levels, indicating CO 2 was no longer a transformation product. PCE transformation resulted in the following percentage of products formed: cDCE (60%), VC (36%), and ethene (4%). Incomplete propionate fermentation was also observed, consistent with the build-up of CF and the decrease in H 2 concentrations to approximately 2nM. The results clearly demonstrate that high concentrations of CT were transformed to CO 2 , and effective PCE dehalogenation to ethene was maintained when excess lactate was fed and propionate was effectively fermented. However, when the lactate concentration was reduced, both PCE and CT transformation and propionate fermentation were negatively impacted. Published by Elsevier B.V.

Simultaneous anaerobic transformation of carbon tetrachloride to carbon dioxide and tetrachloroethene to ethene in a continuous flow column

NASA Astrophysics Data System (ADS)

Azizian, Mohammad F.; Semprini, Lewis

2017-08-01

The simultaneous anaerobic transformation of tetrachloroethene (PCE) and carbon tetrachloride (CT) was evaluated in a continuous flow column. The column was packed with quartz sand and bioaugmented with the Evanite culture (EV) that is capable of transforming PCE to ethene. Azizian and Semprini (2016) reported that PCE and CT could be simultaneously transformed in the column, with PCE (0.1 mM) transformed mainly to ethene and CT (0.015 mM) to chloroform (CF) (20%) and an unknown transformation product, likely carbon dioxide (CO2). The fermentation of propionate, formed from lactate fermentation, was inhibited after the transformation of CT, likely from the exposure to CF. Reported here is the second phase of that study where a second bioaugmentation of the EV culture was made to reintroduce a lactate and propionate fermenting population to the column. Effective lactate and propionate fermentation were restored with a H2 concentration of 25 nM maintained in the column effluent. PCE (0.1 mM) was effectively transformed to ethene ( 98%) and vinyl chloride (VC) ( 2%). Unlabeled CT (0.015 to 0.03 mM) was completely transformed with a transient build-up of CF and chloromethane (CM), which were subsequently removed below their detection limits. A series of transient tests were initiated through the addition of carbon-13 labeled CT (13CT), with concentrations gradually increased from 0.03 to 0.10 mM. GC-MS analysis of the column effluent showed that 13C labeled CO2 (13CO2) was formed, ranging from 82 to 93% of the 13CT transformed, with the transient increases in 13CO2 associated with the increased concentration of 13CT. A modified COD analysis indicated a lesser amount of 13CT (18%) was transformed to soluble products, while 13CO2 represented 82% the 13CT transformed. In a final transient test, the influent lactate concentration was decreased from 1.1 to 0.67 mM. The transformation of both CT and PCE changed dramatically. Only 59% of the 13CT was transformed, primarily to CF. 13CO2 concentrations gradually decreased to background levels, indicating CO2 was no longer a transformation product. PCE transformation resulted in the following percentage of products formed: cDCE (60%), VC (36%), and ethene (4%). Incomplete propionate fermentation was also observed, consistent with the build-up of CF and the decrease in H2 concentrations to approximately 2 nM. The results clearly demonstrate that high concentrations of CT were transformed to CO2, and effective PCE dehalogenation to ethene was maintained when excess lactate was fed and propionate was effectively fermented. However, when the lactate concentration was reduced, both PCE and CT transformation and propionate fermentation were negatively impacted.

Comparative uptake from sea water and tissue distribution of 60Co in marine mollusks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carvalho, F.P.

Five different species of marine mollusks, Mytilus galloprovincialis Lmk., Tapes decussatus L., Cerastoderma (Cardium) edule (L.), Donax vittatus (da Costa) and Patella vulgata L., were exposed to /sup 60/Co-labelled sea water under laboratory conditions. After a 1-mo exposure, tested species reached different whole-body /sup 60/Co concentration factors (CF) over radioactive sea water of 73 +/- 27, 22 +/- 10, 84 +/- 25, 6.3 +/- 1.4 and 31 +/- 10, respectively, which are not dependent upon the size of mollusks. Equations for the experimental uptake curves, obtained using a multi-exponential model, indicate that /sup 60/Co uptake by mollusks involves two ormore » three compartments, according to the species. In all species, the larger compartments turn over with long biological half-lives, dependent upon species. At the beginning of the experiment, /sup 60/CoCl2 added to sea water was mainly in cationic forms. These forms were progressively converted into anionic plus neutral forms most likely due to complex formation with organic ligands. With time this physico-chemical evolution had a lowering effect on /sup 60/Co bioaccumulation by mollusks. Analysis of /sup 60/Co in tissues revealed that Donax shell and mantle do not accumulate the radionuclide in great quantities, generating the low whole-body concentration factor found. In contrast, shell and mantle from all other species displayed variable but high CFs. Shell by itself accounts for more than half of the /sup 60/Co whole-body burden. Among soft tissues, gills and viscera displayed the highest CF and muscle the lowest. From these experiments, one may conclude that significant differences among species do exist regarding Co bioaccumulation potential.« less

Effects of Combined Application of Biogas Slurry and Chemical Fertilizer on Soil Aggregation and C/N Distribution in an Ultisol

PubMed Central

Zheng, Xuebo; Fan, Jianbo; Xu, Lei; Zhou, Jing

2017-01-01

Unreasonable use of chemical fertilizer (CF) on agricultural soil leads to massive losses of soil organic carbon (SOC) and total nitrogen (TN) in tropical and subtropical areas, where soil conditions are unfavorable for aggregate formation. This study evaluated the effects of combined application of biogas slurry (BS) plus CF on soil aggregation and aggregate—associated C/N concentration and storage in an Ultisol. Six treatments included: no fertilizer (T1), CF only (T2), partial (15% (T3), 30% (T4) and 45% (T5)) substitution of TN with BS and BS only (T6). Soil mechanical—stable aggregates (MSAs) formation and stability as well as MSAs—associated C/N concentration and storage were observed in different aggregate sizes (>5, 5–2, 2–1, 1.0–0.5, 0.50–0.25 and <0.25 mm). The proportion of MSAs >5 mm significantly increased with BS substitution (T5), while the proportions of MSAs 1.0–0.5 mm, MSAs 0.50–0.25 mm and MSAs <0.25 mm significantly decreased. Both mean weight diameter and geometric mean diameter were highest in T5, which improved soil aggregation stability as well as resulted in significantly higher SOC and TN concentrations and storage in MSAs >0.5 mm that constituted 72–82% of MSAs. Stepwise regression analysis showed that MSAs >5 mm, SOC in MSAs >5 mm and TN in MSAs >5 mm were the dominant variables affecting aggregate stability. Meanwhile SOC in MSAs <0.25 mm and TN in MSAs 2–1 mm were independent variables affecting SOC and TN concentrations in bulk soils. Therefore, certain rate of combined application of BS plus CF is an effective, eco—friendly way to improve soil quality in an Ultisol. PMID:28125647

A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function.

PubMed

Rubenstein, R C; Zeitlin, P L

1998-02-01

Sodium 4-phenylbutyrate (Buphenyl, 4PBA) is a new FDA approved drug for management of urea cycle disorders. We have previously presented data suggesting that 4PBA, at clinically achievable concentrations, induces CFTR channel function on the plasma membrane of deltaF508-expressing cystic fibrosis (CF) airway epithelial cells in vitro (Rubenstein, R. C., and P. L. Zeitlin, 1997. J. Clin. Invest. 100:2457-2463). We hypothesized that 4PBA would induce epithelial CFTR function in vivo in individuals homozygous for deltaF508-CFTR. A randomized, double-blind, placebo-controlled trial in 18 deltaF508-homozygous patients with CF was performed with the maximum approved adult dose of 4PBA, 19 grams p.o. divided t.i.d., given for 1 wk. Nasal potential difference (NPD) response patterns and sweat chloride concentrations were determined before and after study drug treatment, and 4PBA and metabolites were assayed in plasma and urine at the end of study drug treatment. Subjects in the 4PBA group demonstrated small, but statistically significant improvements of the NPD response to perfusion of an isoproterenol/amiloride/chloride-free solution; this measure reflects epithelial CFTR function and is highly discriminatory between patients with and without CF. Subjects who had received 4PBA did not demonstrate significantly reduced sweat chloride concentrations or alterations in the amiloride-sensitive NPD. Side effects due to drug therapy were minimal and comparable in the two groups. These data are consistent with 4PBA therapy inducing CFTR function in the nasal epithelia of deltaF508-homozygous CF patients.

Association of serum uric acid with aortic stiffness and pressure in a Chinese workplace setting.

PubMed

Chen, Xin; Li, Yan; Sheng, Chang-Sheng; Huang, Qi-Fang; Zheng, Yang; Wang, Ji-Guang

2010-04-01

In the present analysis, we investigated the association of serum uric acid with aortic stiffness and pressure as measured by carotid-femoral pulse wave velocity (cf-PWV) and central systolic blood pressure (SBP), respectively. Our study was conducted in the framework of cardiovascular health examinations for the employees of a factory and their family members (ages 15-79 years). We performed arterial measurements using the SphygmoCor device. Hyperuricemia was defined as a serum uric acid concentration of at least 420 micromol/l in men and 360 micromol/l in women. The 940 study participants included 207 (22.0%) hypertensive patients, of whom 92 (9.8%) took antihypertensive medication. Men (n = 620), compared with women (n = 320), had significantly (P < or = 0.03) higher serum uric acid concentration (363 +/- 76 vs. 272 +/- 64 micromol/l), prevalence of hyperuricemia (17.9% vs. 7.5%), cf-PWV (7.41 vs. 7.16 m/s), and central SBP (114.4 vs. 108.8 mm Hg). Both before and after adjustment for age, serum uric acid was significantly (P < or = 0.02) and positively associated with cf-PWV and central SBP in all subjects and in men and women separately. After full adjustment for covariates, the association with cf-PWV remained statistically significant (P < or = 0.009) in all subjects and men, and with central SBP in all subjects only. Categorical analyses were confirmatory. In all subjects, patients with hyperuricemia had significantly (P = 0.03) higher cf-PWV (7.51 vs. 7.29 m/s) and central SBP (114.9 vs. 112.1 mm Hg) than those with normal serum uric acid. Serum uric acid was associated with aortic stiffness and pressure in a Chinese workplace setting, especially in men.

Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation

PubMed Central

Cowley, Elise S.; Kopf, Sebastian H.; LaRiviere, Alejandro

2015-01-01

ABSTRACT Severe and persistent bacterial lung infections characterize cystic fibrosis (CF). While several studies have documented the microbial diversity within CF lung mucus, we know much less about the inorganic chemistry that constrains microbial metabolic processes and their distribution. We hypothesized that sputum is chemically heterogeneous both within and between patients. To test this, we measured microprofiles of oxygen and sulfide concentrations as well as pH and oxidation-reduction potentials in 48 sputum samples from 22 pediatric patients with CF. Inorganic ions were measured in 20 samples from 12 patients. In all cases, oxygen was depleted within the first few millimeters below the sputum-air interface. Apart from this steep oxycline, anoxia dominated the sputum environment. Different sputum samples exhibited a broad range of redox conditions, with either oxidizing (16 mV to 355 mV) or reducing (−300 to −107 mV) potentials. The majority of reduced samples contained hydrogen sulfide and had a low pH (2.9 to 6.5). Sulfide concentrations increased at a rate of 0.30 µM H2S/min. Nitrous oxide was detected in only one sample that also contained sulfide. Microenvironmental variability was observed both within a single patient over time and between patients. Modeling oxygen dynamics within CF mucus plugs indicates that anoxic zones vary as a function of bacterial load and mucus thickness and can occupy a significant portion of the mucus volume. Thus, aerobic respiration accounts only partially for pathogen survival in CF sputum, motivating research to identify mechanisms of survival under conditions that span fluctuating redox states, including sulfidic environments. PMID:26220964

Finite Element Analysis of the Endodontically-treated Maxillary Premolars restored with Composite Resin along with Glass Fiber Insertion in Various Positions.

PubMed

Navimipour, Elmira Jafari; Firouzmandi, Maryam; Mirhashemi, Fatemeh Sadat

2015-04-01

This study evaluated the effect of three methods of glass fiber insertion on stress distribution pattern and cusp movement of the root-filled maxillary premolars using finite element method (FEM) analysis. A three-dimensional (3 D) FEM model of a sound upper premolar tooth and four models of root-filled upper premolars with mesiocclusodistal (MOD) cavities were molded and restored with: (1) Composite resin only (NF); (2) Composite resin along with a ribbon of glass fiber placed in the occlusal third (OF); (3) Composite resin along with a ribbon of glass fiber placed circumferentially in the cervical third (CF), and (4) Composite resin along with occlusal and circumferential fibers (OCF). A static vertical load was applied to calculate the stress distributions. Structural analysis program by Solidworks were used for FEM analysis. Von-Mises stress values and cusp movements induced by occlusal loading were evaluated. Maximum Von-Mises stress of enamel occurred in sound tooth, followed by NF, CF, OF and OCF. Maximum Von-Mises stress of dentin occurred in sound tooth, followed by OF, OCF, CF and NF. Stress distribution patterns of OF and OCF were similar. Maximum overall stress values were concentrated in NF. Although stress distribution patterns of NF and CF were found as similar, CF showed lower stress values. Palatal cusp movement was more than buccal cusp in all of the models. The results of our study indicated that while the circumferential fiber had little effect on overall stress concentration, it provided a more favorable stress distribution pattern in cervical region. The occlusal fiber reduced the average stress in the entire structure but did not reduce cuspal movement. Incorporating glass fiber in composite restorations may alter the stress state within the structure depending on fiber position.

In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR.

PubMed Central

Rubenstein, R C; Egan, M E; Zeitlin, P L

1997-01-01

The most common cystic fibrosis transmembrane conductance regulator mutation, delta F508-CFTR, is a partially functional chloride channel that is retained in the endoplasmic reticulum and degraded. We hypothesize that a known transcriptional regulator, sodium 4-phenylbutyrate (4PBA), will enable a greater fraction of delta F508-CFTR to escape degradation and appear at the cell surface. Primary cultures of nasal polyp epithelia from CF patients (delta F508 homozygous or heterozygous), or the CF bronchial epithelial cell line IB3-1 (delta F508/W1282X) were exposed to 4PBA for up to 7 d in culture. 4PBA treatment at concentrations of 0.1 and 2 mM resulted in the restoration of forskolin-activated chloride secretion. Protein kinase A-activated, linear, 10 pS chloride channels appeared at the plasma membrane of IB3-1 cells at the tested concentration of 2.5 mM. Treatment of IB3-1 cells with 0.1-1 mM 4PBA and primary nasal epithelia with 5 mM 4PBA also resulted in the appearance of higher molecular mass forms of CFTR consistent with addition and modification of oligosaccharides in the Golgi apparatus, as detected by immunoblotting of whole cell lysates with anti-CFTR antisera. Immunocytochemistry in CF epithelial cells treated with 4PBA was consistent with increasing amounts of delta F508-CFTR. These data indicate that 4PBA is a promising pharmacologic agent for inducing correction of the CF phenotype in CF patients carrying the delta F508 mutation. PMID:9366560

In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR.

PubMed

Rubenstein, R C; Egan, M E; Zeitlin, P L

1997-11-15

The most common cystic fibrosis transmembrane conductance regulator mutation, delta F508-CFTR, is a partially functional chloride channel that is retained in the endoplasmic reticulum and degraded. We hypothesize that a known transcriptional regulator, sodium 4-phenylbutyrate (4PBA), will enable a greater fraction of delta F508-CFTR to escape degradation and appear at the cell surface. Primary cultures of nasal polyp epithelia from CF patients (delta F508 homozygous or heterozygous), or the CF bronchial epithelial cell line IB3-1 (delta F508/W1282X) were exposed to 4PBA for up to 7 d in culture. 4PBA treatment at concentrations of 0.1 and 2 mM resulted in the restoration of forskolin-activated chloride secretion. Protein kinase A-activated, linear, 10 pS chloride channels appeared at the plasma membrane of IB3-1 cells at the tested concentration of 2.5 mM. Treatment of IB3-1 cells with 0.1-1 mM 4PBA and primary nasal epithelia with 5 mM 4PBA also resulted in the appearance of higher molecular mass forms of CFTR consistent with addition and modification of oligosaccharides in the Golgi apparatus, as detected by immunoblotting of whole cell lysates with anti-CFTR antisera. Immunocytochemistry in CF epithelial cells treated with 4PBA was consistent with increasing amounts of delta F508-CFTR. These data indicate that 4PBA is a promising pharmacologic agent for inducing correction of the CF phenotype in CF patients carrying the delta F508 mutation.

Prognostic and diagnostic value of eosinopenia, C-reactive protein, procalcitonin, and circulating cell-free DNA in critically ill patients admitted with suspicion of sepsis.

PubMed

Garnacho-Montero, Jose; Huici-Moreno, María J; Gutiérrez-Pizarraya, Antonio; López, Isabel; Márquez-Vácaro, Juan Antonio; Macher, Hada; Guerrero, Juan Manuel; Puppo-Moreno, Antonio

2014-06-05

The aims of this study were to assess the reliability of circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of infections in patients with systemic inflammatory response syndrome (SIRS) and their prognostic values in a cohort of critically ill patients. We conducted a prospective cohort study in a medical-surgical intensive care unit of a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit (ICU) and a second determination 24 hours later. DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene. One hundred and sixty consecutive patients were included: 43 SIRS without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or eosinophil count, were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94). Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score. PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers. Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS. PCT is of value especially for infection identification in patients with SIRS at admission to the ICU.

[Characteristics of soil ammonia-oxidation microbial communities in different subtropical forests, China].

PubMed

Li, Yong-Chun; Liu, Bu-Rong; Guo, Shuai; Wu, Qi-Feng; Qin, Hua; Wu, Jia-Sen; Xu, Qiu-Fang

2014-01-01

To investigate the effects of different forest stands in subtropical China on the communities of soil ammonia-oxidizing microorganisms, we characterized the abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and the community structure of AOA in soils under stands of broad-leaved (BF) , Chinese fir (CF) , Pinus massoniana (PF) and moso bamboo (MB) forests using real-time quantitative PCR and denaturing gradient gel electrophoresis (DGGE). The results showed that the AOA gene copy numbers (1.62 x 10(6)-1.88 x 10(7) per gram of dry soil) were significantly higher than those of AOB genes (2.41 x 10(5)-4.36 x 10(5) per gram of dry soil). Significantly higher soil AOA abundance was detected in the MB than that in the CF (P < 0.05), and the latter was significantly higher than that in the BF and PF soils (P < 0.05). There were no significant differences in the soil AOB abundance among the four forest stands. As indicated by DGGE pattern, soil AOA species varied among the four forest stands. There was a difference in the soil AOA communities between the CF and MB stands. The AOA demonstrated a competitive advantage over the AOB in the soils under these major subtropical forests. Soil pH, concentrations of soil available potassium and organic carbon as well as the forest type were the main factors that influence the variation of AOA community structure and diversity.

Biogeochemical features of maple and dandelion in Eastern Administrative District of Moscow

NASA Astrophysics Data System (ADS)

Vlasov, Dmitry

2014-05-01

Today more than half of world population and 73% of population in Russia live in cities. Moscow is the only one megacity in Russia with the population more than 11 million. The main source of technogenic impact in Moscow is transport. Plants can be used as indicators of urban environment heavy metals and metalloids (HM) pollution. Large scale biogeochemical research was done in Eastern Administrative District of Moscow. Apart from transport there are many industrial sources of pollution: metalworking, mechanical engineering, chemical, energetic and incinerator. This study focuses on detection of HM composition of woody plant leaves (maple - Acer platanoides) and herbaceous species leaves (dandelion - Taraxacum officinale). Plant material was collected on a regular greed with a step of 500-700 m. Background plants were sampled at 40 km west away from the city. Determination of Fe, Mn, Mo, Cd, Pb, Zn, Cu, As, Sb in plants was done using atomic absorption spectrometry after washing, drying and digestion with HNO3+H2O2. It was revealed that dandelion accumulates (index - concentration factors CF relatively background) Mo13Fe6Pb5Cd4.5As4Sb3, while maple Sb13As5.5Fe3Mo2Pb,Zn1.5. Geochemical specialization of plants in functional zones (industrial, transport, recreational, agricultural, residential areas with high-, middle- and low-rise buildings) was identified. The highest CF were determined for Mo in dandelion of all zones except industrial. In which the most accumulated elements are Fe and Mo, as well as Pb10As6Sb5Cu2. Arsenic is accumulated by dandelion in all zones. Copper is not concentrated by herbaceous species because of antagonism between Mo and Cu. The highest CF were determined for HM in maple of industrial zone. There trees concentrate Sb and As9Fe7Mo6Pb3Zn2. In the other zones levels of CF are lower in 2-5 times. Dandelion and maple don't accumulate Mn because of antagonism between Zn, Mo and Mn. Urban plants condition is estimated by the ratio between toxic (Cd, As, Sb, Pb) and essential (Cu, Fe, Mn, Mo, Zn) elements. For evaluation of intensity of photosynthesis and plants growth can be used Fe/Mn, Zn/Mn, Cu/Mn and Mo/Mn ratios. In dandelion and maple Fe/Mn is 6.6 and 3.3 times higher than in background vegetation, Pb/Mn - 5.5 and 2.5 times, (Cd+As+Sb+Pb)/(Cu+Fe+Mn+Mo+Zn) - 2.9 and 1.6 times respectively. In industrial, transport zones and residential area with high-rise buildings the largest increase of those ratios were discovered. Differences in geochemical specialization were shown by Sb/Mo ratio: in dandelion it is 5 times lower than in background plants, while in maple it is 4.5 times higher. The same situation was defined for As/Mo. Strong positive linear relationship between Sb deposition rates and Sb concentrations in maple was calculated (r=0.86). Furthermore moderate positive linear relationships between Cd concentrations in soils and dandelion (r=0.69), concentrations of mobile forms of Pb and Sb in soils and maple (r=0.67 and 0.66), Fe deposition rates and concentrations of this element in maple (r=0.51) were revealed.

Cell-free DNA characteristics and chimerism analysis in patients after allogeneic cell transplantation.

PubMed

Duque-Afonso, Jesus; Waterhouse, Miguel; Pfeifer, Dietmar; Follo, Marie; Duyster, Justus; Bertz, Hartmut; Finke, Jürgen

2018-02-01

Cell-free DNA (cfDNA) isolated from plasma or serum has received increasing interest for diagnostic applications in pregnancy, solid tumors and solid organ transplantation. The reported clinical usefulness of cfDNA obtained from plasma or serum in patients undergoing allogeneic cell transplantation (alloHSCT) is scarce. To analyze the potential clinical utility of cfDNA chimerism analysis after alloHSCT. A total of 196 samples obtained from 110 patients were investigated for their chimeric status both in peripheral blood and plasma using standard PCR for microsatellite amplification. Plasma DNA size distribution was analyzed using capillary electrophoresis. The mean cfDNA concentration in the transplanted patients was 469ng/ml (range: 50-10,700ng/ml). The size range of almost 80% of the analyzed fragments was between 80 and 200bp. In 41 out of the 110 patients included in the study a mixture of donor and recipient plasma cfDNA was detected. There was a statistically significant difference in the percentage of plasma mixed chimerism between the patients without transplant related complications and the patients with either GvHD (p<0.05) or relapse (p<0.01). In those patients who showed improvement of GvHD also displayed a decrease in the observable percentage of recipient cfDNA during GvHD treatment. In patients without improvement or even with worsening of acute GvHD, stable or increasing levels of recipient cfDNA were detected. cfDNA in combination with peripheral blood and bone marrow cell chimerism analysis might improve its utility in the clinic in particular in those patients with clinical complications after alloHSCT. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Carbon-fluorine bond activation coupled with carbon-hydrogen bond formation alpha to iridium: kinetics, mechanism, and diastereoselectivity.

PubMed

Garratt, Shaun A; Hughes, Russell P; Kovacik, Ivan; Ward, Antony J; Willemsen, Stefan; Zhang, Donghui

2005-11-09

Reactions of iridium(fluoroalkyl)hydride complexes CpIr(PMe(3))(CF(2)R(F))Y (R(F) = F, CF(3); Y = H, D) with LutHX (Lut = 2,6-dimethylpyridine; X = Cl, I) results in C-F activation coupled with hydride migration to give CpIr(PMe(3))(CYFR(F))X as variable mixtures of diastereomers. Solution conformations and relative diastereomer configurations of the products have been determined by (19)F{(1)H}HOESY NMR to be (S(C), S(Ir))(R(C), R(Ir)) for the kinetic diastereomer and (R(C), S(Ir))(S(C), R(Ir)) for its thermodynamic counterpart. Isotope labeling experiments using LutDCl/CpIr(PMe(3))(CF(2)R(F))H and CpIr(PMe(3))(CF(2)R(F))D/LutHCl) showed that, unlike a previously studied system, H/D exchange is faster than protonation of the alpha-CF bond, giving an identical mixture of product isotopologues from both reaction mixtures. The kinetic rate law shows a first-order dependence on the concentration of iridium substrate, but a half-order dependence on that of LutHCl; this is interpreted to mean that LutHCl dissociates to give HCl as the active protic source for C-F bond activation. Detailed kinetic studies are reported, which demonstrate that lack of complete diastereoselectivity is not a function of the C-F bond activation/H migration steps but that a cationic intermediate plays a double role in loss of diastereoselectivity; the intermediate can undergo epimerization at iridium before being trapped by halide and can also catalyze the epimerization of kinetic diastereomer product to thermodynamic product. A detailed mechanism is proposed and simulations performed to fit the kinetic data.

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

PubMed Central

Kevadiya, Bhavesh D.; Woldstad, Christopher; Ottemann, Brendan M.; Dash, Prasanta; Sajja, Balasrinivasa R.; Lamberty, Benjamin; Morsey, Brenda; Kocher, Ted; Dutta, Rinku; Bade, Aditya N.; Liu, Yutong; Callen, Shannon E.; Fox, Howard S.; Byrareddy, Siddappa N.; McMillan, JoEllyn M.; Bronich, Tatiana K.; Edagwa, Benson J.; Boska, Michael D.; Gendelman, Howard E.

2018-01-01

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy. PMID:29290806

Performance of cell-penetrating peptide-linked polymers physically mixed with poorly membrane-permeable molecules on cell membranes.

PubMed

Sakuma, Shinji; Suita, Masaya; Yamamoto, Takafumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Nakajima, Noriko; Shinkai, Norihiro; Yamauchi, Hitoshi; Hiwatari, Ken-Ichiro; Hashizume, Akio; Tachikawa, Hiroyuki; Kimura, Ryoji; Ishimaru, Yuki; Kasai, Atsushi; Maeda, Sadaaki

2012-05-01

We are investigating a new class of penetration enhancers that enable poorly membrane-permeable molecules physically mixed with them to effectively penetrate cell membranes without their concomitant cellular uptake. Since we previously revealed that poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, significantly enhanced the nasal absorption of insulin, we examined the performance of the polymers on cell membranes. When Caco-2 cells were incubated with 5(6)-carboxyfluorescein (CF) for 30 min, approximately 0.1% of applied CF was internalized into the cells. This poor membrane permeability was dramatically enhanced by d-octaarginine-linked polymers; a 25-fold increase in the cellular uptake of CF was observed when the polymer concentration was adjusted to 0.2mg/mL. None of the individual components, for example, d-octaarginine, had any influence on CF uptake, demonstrating that only d-octaarginine anchored chemically to the polymeric platform enhanced the membrane permeation of CF. The polymer-induced CF uptake was consistently high even when the incubation time was extended to 120 min. Confocal laser scanning microphotographs of cells incubated with d-octaarginine-linked polymers bearing rhodamine red demonstrated that the cell outline was stained with red fluorescence. The polymer-induced CF uptake was significantly suppressed by 5-(N-ethyl-N-isopropyl)amiloride, which is an inhibitor of macropinocytosis. Results indicated that d-octaarginine-linked polymers remained on the cell membrane and poorly membrane-permeable CF was continuously internalized into cells mainly via macropinocytosis repeated for the individual peptidyl branches in the polymer backbone. Copyright © 2012 Elsevier B.V. All rights reserved.

Attention and memory impairments in pediatric patients with cystic fibrosis and inflammatory bowel disease in comparison to healthy controls.

PubMed

Piasecki, Bartosz; Stanisławska-Kubiak, Maia; Strzelecki, Wojciech; Mojs, Ewa

2017-10-01

The main aim of the study was to analyze and compare attention and memory performance in pediatric patients with cystic fibrosis (CF), inflammatory bowel disease (IBD) and in healthy controls. 28 patients with CF, 30 patients with IBD and 30 healthy subjects took part in the study (all in age range of 7-17). All subjects were in intellectual norm. To analyze the functioning of attention, the d2 Test of Attention by Brickenkamp (d2 test) was applied. Memory performance was assessed using the Benton Visual Retention Test (BVRT) and the Trial of 10 words. The CF and IBD groups committed significantly more errors in the d2 test than the healthy controls. The CF group also had significantly higher fluctuation rates and received significantly lower scores in overall concentration performance than the control group. Patients with CF made more mistakes and had fewer correct memory projections in BVRT than the healthy controls. Patients with IBD committed significantly more errors in BVRT than the control group. Patients with CF and IBD also got significantly lower scores in the Trial of 10 words than the control group. Pediatric patients with CF and IBD performed more poorly than the healthy controls on attention and memory tests. More distinct cognitive impairments were observed in the CF group. Further research is needed to find the underlying mechanisms and clinical and/or functional significance of observed cognitive deficits. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.

PubMed

Holland, Anne E; Wilson, John W; Kotsimbos, Thomas C; Naughton, Matthew T

2003-08-01

and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p < 0.01). A mixed respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p < 0.01). The mean concentrations of plasma chloride (95.1 +/- 4.9 vs 99.8 +/- 5.2 mmol/L, respectively; p < 0.01) and sodium (136.5 +/- 2.8 vs 140.4 +/- 4.5 mmol/L, respectively; p < 0.01) were significantly lower in the CF group, and the levels of serum albumin were significantly reduced (27.4 +/- 5.8 vs 33.7 +/- 4.8 mmol/L, respectively; p < 0.01). Metabolic alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.

Guidelines for the clinical management and follow-up of infants with inconclusive cystic fibrosis diagnosis through newborn screening.

PubMed

Sermet-Gaudelus, I; Brouard, J; Audrézet, M-P; Couderc Kohen, L; Weiss, L; Wizla, N; Vrielynck, S; LLerena, K; Le Bourgeois, M; Deneuville, E; Remus, N; Nguyen-Khoa, T; Raynal, C; Roussey, M; Girodon, E

2017-12-01

Neonatal screening for cystic fibrosis (CF) can detect infants with elevated immunoreactive trypsinogen (IRT) levels and inconclusive sweat tests and/or CFTR DNA results. These cases of uncertain diagnosis are defined by (1) either the presence of at most one CF-associated cystic fibrosis transmembrane conductance regulator (CFTR) mutation with sweat chloride values between 30 and 59mmol/L or (2) two CFTR mutations with at least one of unknown pathogenic potential and a sweat chloride concentration below 60mmol/L. This encompasses various clinical situations whose progression cannot be predicted. In these cases, a sweat chloride test has to be repeated at 12 months, and if possible at 6 and 24 months of life along with extended CFTR sequencing to detect rare mutations. When the diagnosis is not definite, CFTR functional explorations may provide a better understanding of CFTR dysfunction. The initial evaluation of these infants must be conducted in dedicated CF reference centers and should include bacteriological sputum analysis, chest radiology, and fecal elastase assay. The primary care physicians in charge of these patients should be familiar with the current management of CF and should work in collaboration with CF centers. A follow-up should be performed in a CF reference center at 3, 6, and 12 months of life and every year thereafter. Any symptom indicative of CF requires immediate reevaluation of the diagnosis. These guidelines were established by the "neonatal screening and difficult diagnoses" working group of the French CF society. Their objective is to standardize the management of infants with unclear diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities

PubMed Central

Adam, Ryan J.; Hisert, Katherine B.; Dodd, Jonathan D.; Grogan, Brenda; Launspach, Janice L.; Barnes, Janel K.; Gallagher, Charles G.; Sieren, Jered P.; Gross, Thomas J.; Fischer, Anthony J.; Cavanaugh, Joseph E.; Hoffman, Eric A.; Singh, Pradeep K.; Welsh, Michael J.; McKone, Edward F.; Stoltz, David A.

2016-01-01

BACKGROUND. Airflow obstruction is common in cystic fibrosis (CF), yet the underlying pathogenesis remains incompletely understood. People with CF often exhibit airway hyperresponsiveness, CF transmembrane conductance regulator (CFTR) is present in airway smooth muscle (ASM), and ASM from newborn CF pigs has increased contractile tone, suggesting that loss of CFTR causes a primary defect in ASM function. We hypothesized that restoring CFTR activity would decrease smooth muscle tone in people with CF. METHODS. To increase or potentiate CFTR function, we administered ivacaftor to 12 adults with CF with the G551D-CFTR mutation; ivacaftor stimulates G551D-CFTR function. We studied people before and immediately after initiation of ivacaftor (48 hours) to minimize secondary consequences of CFTR restoration. We tested smooth muscle function by investigating spirometry, airway distensibility, and vascular tone. RESULTS. Ivacaftor rapidly restored CFTR function, indicated by reduced sweat chloride concentration. Airflow obstruction and air trapping also improved. Airway distensibility increased in airways less than 4.5 mm but not in larger-sized airways. To assess smooth muscle function in a tissue outside the lung, we measured vascular pulse wave velocity (PWV) and augmentation index, which both decreased following CFTR potentiation. Finally, change in distensibility of <4.5-mm airways correlated with changes in PWV. CONCLUSIONS. Acute CFTR potentiation provided a unique opportunity to investigate CFTR-dependent mechanisms of CF pathogenesis. The rapid effects of ivacaftor on airway distensibility and vascular tone suggest that CFTR dysfunction may directly cause increased smooth muscle tone in people with CF and that ivacaftor may relax smooth muscle. FUNDING. This work was funded in part from an unrestricted grant from the Vertex Investigator-Initiated Studies Program. PMID:27158673

Glycolysis of carbon fiber-epoxy unidirectional mat catalysed by sodium hydroxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaini, Mariana Binti Mohd; Badri, Khairiah Haji

2014-09-03

This study was conducted to recycle carbon fibre-epoxy (CFRP) composite in woven sheet/ mat form. The CFRP was recycled through glycolysis with polyethlyene glycol (PEG 200) as the solvent. The CFRP was loaded into the solvent at a ratio of 4:1 (w/w). PEG200 was diluted with water to a ratio of 80:20 (v/v). This reaction was catalysed by sodium hydroxide (NaOH) solution with varying concentrations at 1.5, 1.7 and 1.9% (w/v). The glycolysis was conducted at 180-190 °C. The recovered CF (rCF) was analysed using Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray (EDX) while themore » degraded solution was analysed using FTIR and the epoxy content was determined. The FTIR spectrum of the rCF exhibited the disappearance of the COC peak belonged to epoxy and supported by the SEM micrographs that showed clear rCF. On the other hand, the analysed filtrate detected the disappearance of oxygen peak element in the EDX spectrum for all rCF samples. This gave an indication that the epoxy resin has been removed from the surface of the carbon fiber.« less

Glycolysis of carbon fiber-epoxy unidirectional mat catalysed by sodium hydroxide

NASA Astrophysics Data System (ADS)

Zaini, Mariana Binti Mohd; Badri, Khairiah Haji

2014-09-01

This study was conducted to recycle carbon fibre-epoxy (CFRP) composite in woven sheet/ mat form. The CFRP was recycled through glycolysis with polyethlyene glycol (PEG 200) as the solvent. The CFRP was loaded into the solvent at a ratio of 4:1 (w/w). PEG200 was diluted with water to a ratio of 80:20 (v/v). This reaction was catalysed by sodium hydroxide (NaOH) solution with varying concentrations at 1.5, 1.7 and 1.9% (w/v). The glycolysis was conducted at 180-190 °C. The recovered CF (rCF) was analysed using Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray (EDX) while the degraded solution was analysed using FTIR and the epoxy content was determined. The FTIR spectrum of the rCF exhibited the disappearance of the COC peak belonged to epoxy and supported by the SEM micrographs that showed clear rCF. On the other hand, the analysed filtrate detected the disappearance of oxygen peak element in the EDX spectrum for all rCF samples. This gave an indication that the epoxy resin has been removed from the surface of the carbon fiber.

Mechanical property degradation and microstructural evolution of cast austenitic stainless steels under short-term thermal aging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lach, Timothy G.; Byun, Thak Sang; Leonard, Keith J.

We performed mechanical testing and microstructural characterization on short-term thermally aged cast austenitic stainless steels (CASS) to understand the severity and mechanisms of thermal-aging degradation experienced during extended operation of light water reactor (LWR) coolant systems. Four CASS materials–CF3, CF3M, CF8, and CF8M–were thermally aged for 1500 h at 290 °C, 330 °C, 360 °C, and 400 °C. All four alloys experienced insignificant change in strength and ductility properties but a significant reduction in absorbed impact energy. The primary microstructural and compositional changes during thermal aging were spinodal decomposition of the δ-ferrite into α/α', precipitation of G-phase in the δ-ferrite,more » segregation of solute to the austenite/ferrite interphase boundary, and growth of M 23C 6 carbides on the austenite/ferrite interphase boundary. These changes were shown to be highly dependent on chemical composition, particularly the concentration of C and Mo, and aging temperature. Finally, the low C, high Mo CF3M alloys experienced the most spinodal decomposition and G-phase precipitation coinciding the largest reduction in impact properties.« less

Mechanical property degradation and microstructural evolution of cast austenitic stainless steels under short-term thermal aging

NASA Astrophysics Data System (ADS)

Lach, Timothy G.; Byun, Thak Sang; Leonard, Keith J.

2017-12-01

Mechanical testing and microstructural characterization were performed on short-term thermally aged cast austenitic stainless steels (CASS) to understand the severity and mechanisms of thermal-aging degradation experienced during extended operation of light water reactor (LWR) coolant systems. Four CASS materials-CF3, CF3M, CF8, and CF8M-were thermally aged for 1500 h at 290 °C, 330 °C, 360 °C, and 400 °C. All four alloys experienced insignificant change in strength and ductility properties but a significant reduction in absorbed impact energy. The primary microstructural and compositional changes during thermal aging were spinodal decomposition of the δ-ferrite into α/α‧, precipitation of G-phase in the δ-ferrite, segregation of solute to the austenite/ferrite interphase boundary, and growth of M23C6 carbides on the austenite/ferrite interphase boundary. These changes were shown to be highly dependent on chemical composition, particularly the concentration of C and Mo, and aging temperature. The low C, high Mo CF3M alloys experienced the most spinodal decomposition and G-phase precipitation coinciding the largest reduction in impact properties.

Mechanical property degradation and microstructural evolution of cast austenitic stainless steels under short-term thermal aging

DOE PAGES

Lach, Timothy G.; Byun, Thak Sang; Leonard, Keith J.

2017-07-31

We performed mechanical testing and microstructural characterization on short-term thermally aged cast austenitic stainless steels (CASS) to understand the severity and mechanisms of thermal-aging degradation experienced during extended operation of light water reactor (LWR) coolant systems. Four CASS materials–CF3, CF3M, CF8, and CF8M–were thermally aged for 1500 h at 290 °C, 330 °C, 360 °C, and 400 °C. All four alloys experienced insignificant change in strength and ductility properties but a significant reduction in absorbed impact energy. The primary microstructural and compositional changes during thermal aging were spinodal decomposition of the δ-ferrite into α/α', precipitation of G-phase in the δ-ferrite,more » segregation of solute to the austenite/ferrite interphase boundary, and growth of M 23C 6 carbides on the austenite/ferrite interphase boundary. These changes were shown to be highly dependent on chemical composition, particularly the concentration of C and Mo, and aging temperature. Finally, the low C, high Mo CF3M alloys experienced the most spinodal decomposition and G-phase precipitation coinciding the largest reduction in impact properties.« less

Conflict or congruence? Maternal and infant-centric factors associated with shorter exclusive breastfeeding durations among the Tsimane

PubMed Central

Martin, Melanie A.; Garcia, Geni; Kaplan, Hillard S.; Gurven, Michael D.

2016-01-01

Six months of exclusive breastfeeding (EBF) is considered optimal for infant health, though globally most infants begin complementary feeding (CF) earlier—including among populations that practice prolonged breastfeeding. Two frameworks for understanding patterns of early CF emerge in the literature. In the first, maternal and infant needs trade-off, as “maternal-centric” factors—related to time and energy demands, reproductive investment, cultural influences, and structural barriers— favor supplanting breastfeeding with earlier and increased CF. A second framework considers that “infant-centric” factors—related to infant energetic needs—favor CF before six months to supplement breastfeeding. We apply these two frameworks in examining early CF among the Tsimane—a high-fertility, high-mortality, forager-horticulturalist population residing in the Bolivian Amazon. Data were collected from a mixed-longitudinal sample of 161 Tsimane mother-infant pairs from August 2012 – April 2013. Tsimane mothers generally reported introducing CF because of perceived infant needs. However, CF is introduced with continued intensive breastfeeding, and generally coupled with premastication. Risks of earlier CF relative to the minimum hazard (estimated at 5 births) were elevated for lower and higher parity mothers, but were significantly greater only after 9 births. Seventeen percent of mothers reported introducing CF because of low milk supply. Introducing CF because of low milk was most common from 0-3 months of age and among higher parity mothers, which may reflect physiological constraints. Maternal reproductive trade-offs and perceived infant needs may help explain the low prevalence of EBF to six months among other populations in which breastfeeding is not structurally or culturally constrained. PMID:27732906

Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid treatment in infancy.

PubMed

Bregman, Tatiana; Fride, Ester

2011-06-17

Substantial data have been accumulated regarding the molecular basis of cystic fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on brain processes has been the focus of much less attention. We have studied some behavioral parameters, such as motor activity and anxiety level, in a mice model of CF. We have assumed that functioning of the endocannabinoid system could be impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid deficiency is considered a major factor in CF etiology). We have suggested that chronic treatment with cannabinoid receptors agonist during infancy would balance cannabinoid levels and prevent CF-related behavioral alterations. Motor activity and anxiety level were studied in naïve adult CF mice (cftr-deficient mice) and compared with wild-type mice and to CF mice treated chronically with Δ9-tetrahydrocannabinol (Δ9-THC; endocannabinoid receptor agonist) during infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level of anxiety in the plus maze, a month after cessation of treatment. Motor activity decrease and elevated anxiety level were found in adult naïve CF mice compared with wild-type mice. CF mice treated with THC in infancy showed normal motor activity and anxiety levels in adulthood. Motor function alteration and elevated anxiety levels in CF can result from lack of CFTR-channel in neurons and disturbed activity of various brain areas, as well as being secondary and mediated by fatty acids deficiency, altered levels of endocannabinoids and their receptors. It can be suggested that chronic treatment during infancy restores endocannabinoid function and thus prevents behavioral alterations.

Product toxicity and cometabolic competitive inhibition modeling of chloroform and trichloroethylene transformation by methanotrophic resting cells.

PubMed Central

Alvarez-Cohen, L; McCarty, P L

1991-01-01

The rate and capacity for chloroform (CF) and trichloroethylene (TCE) transformation by a mixed methanotrophic culture of resting cells (no exogenous energy source) and formate-fed cells were measured. As reported previously for TCE, formate addition resulted in an increased CF transformation rate (0.35 day-1 for resting cells and 1.5 day-1 for formate-fed cells) and transformation capacity (0.0065 mg of CF per mg of cells for resting cells and 0.015 mg of CF per mg of cells for formate-fed cells), suggesting that depletion of energy stores affects transformation behavior. The observed finite transformation capacity, even with an exogenous energy source, suggests that toxicity was also a factor. CF transformation capacity was significantly lower than that for TCE, suggesting a greater toxicity from CF transformation. The toxicity of CF, TCE, and their transformation products to whole cells was evaluated by comparing the formate oxidation activity of acetylene-treated cells to that of non-acetylene-treated cells with and without prior exposure to CF or TCE. Acetylene arrests the activity of methane monooxygenase in CF and TCE oxidation without halting cell activity toward formate. Significantly diminished formate oxidation by cells exposed to either CR or TCE without acetylene compared with that with acetylene suggests that the solvents themselves were not toxic under the experimental conditions but their transformation products were. The concurrent transformation of CF and TCE by resting cells was measured, and results were compared with predictions from a competitive-inhibition cometabolic transformation model. The reasonable fit between model predictions and experimental observations was supportive of model assumptions. PMID:1905516

Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process

PubMed Central

Choi, Jae Young; Khansaheb, Monal; Joo, Nam Soo; Krouse, Mauri E.; Robbins, Robert C.; Weill, David; Wine, Jeffrey J.

2009-01-01

Chronic bacterial airway infections are the major cause of mortality in cystic fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal gland mucus secretion by sensory neurons that release substance P (SubP). CFTR is an anion channel involved in fluid secretion and mutated in CF; the role of CFTR in secretions stimulated by SubP is unknown. We used optical methods to measure SubP-mediated secretion from human submucosal glands in lung transplant tissue. Glands from control but not CF subjects responded to mucosal chili oil. Similarly, serosal SubP stimulated secretion in more than 60% of control glands but only 4% of CF glands. Secretion triggered by SubP was synergistic with vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal irritants to stimulate airway gland secretion via SubP may be another factor that predisposes the airways to infections. PMID:19381016

Along the way to developing a theory of the program: a re-examination of the conceptual framework as an organizing strategy.

PubMed

Helitzer, Deborah L; Sussman, Andrew L; Hoffman, Richard M; Getrich, Christina M; Warner, Teddy D; Rhyne, Robert L

2014-08-01

Conceptual frameworks (CF) have historically been used to develop program theory. We re-examine the literature about the role of CF in this context, specifically how they can be used to create descriptive and prescriptive theories, as building blocks for a program theory. Using a case example of colorectal cancer screening intervention development, we describe the process of developing our initial CF, the methods used to explore the constructs in the framework and revise the framework for intervention development. We present seven steps that guided the development of our CF: (1) assemble the "right" research team, (2) incorporate existing literature into the emerging CF, (3) construct the conceptual framework, (4) diagram the framework, (5) operationalize the framework: develop the research design and measures, (6) conduct the research, and (7) revise the framework. A revised conceptual framework depicted more complicated inter-relationships of the different predisposing, enabling, reinforcing, and system-based factors. The updated framework led us to generate program theory and serves as the basis for designing future intervention studies and outcome evaluations. A CF can build a foundation for program theory. We provide a set of concrete steps and lessons learned to assist practitioners in developing a CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical accuracy of abnormal cell-free fetal DNA results for the sex chromosomes.

PubMed

Scibetta, Emily W; Gaw, Stephanie L; Rao, Rashmi R; Silverman, Neil S; Han, Christina S; Platt, Lawrence D

2017-12-01

To investigate factors associated with abnormal cell-free DNA (cfDNA) results for sex chromosomes (SCs). This is a retrospective cohort study of abnormal cfDNA results for SC at a referral practice from March 2013 to July 2015. Cell-free DNA results were abnormal if they were positive for SC aneuploidy (SCA), inconclusive, or discordant with ultrasound (US) findings. Primary outcome was concordance with karyotype or postnatal evaluation. Of 50 abnormal cfDNA results for SC, 31 patients (62%) were positive for SCA, 13 (26%) were inconclusive, and 6 (12%) were sex discordant on US. Of SCA results, 19 (61%) were reported as 45,X and 12 (39%) were SC trisomy. Abnormal karyotypes were confirmed in 8/23 (35%) of SC aneuploidy and 1/5 (20%) of inconclusive results. Abnormal SC cfDNA results were associated with in vitro fertilization (P = .001) and twins (P < .001). Sex discordance between cfDNA and US was associated with twin gestation (P < .001). In our cohort, abnormal SC cfDNA results were associated with in vitro fertilization and twins. Our results indicate cfDNA for sex prediction in twins of limited utility. Positive predictive value and sensitivity for SC determination were lower than previously reported. © 2017 John Wiley & Sons, Ltd.

Repurposing tromethamine as inhaled therapy to treat CF airway disease

PubMed Central

Alaiwa, Mahmoud H. Abou; Launspach, Janice L.; Sheets, Kelsey A.; Rivera, Jade A.; Gansemer, Nicholas D.; Taft, Peter J.; Thorne, Peter S.; Welsh, Michael J.; Stoltz, David A.

2016-01-01

In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3– and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3– increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3–-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID:27390778

Antimicrobial peptides in saliva of children with severe early childhood caries.

PubMed

Colombo, Natália H; Ribas, Laís F F; Pereira, Jesse A; Kreling, Paula F; Kressirer, Christine A; Tanner, Anne C R; Duque, Cristiane

2016-09-01

Controversies exist regarding the relationship between the concentrations of antimicrobial peptides (AMPs) and presence of dental caries in children. Thus, the aim of this study was to examine levels of AMPs in saliva of caries-free (CF), early childhood caries (ECC) and severe early childhood caries (S-ECC) children to determine if the levels of these salivary peptides individually or in combinations were related to caries severity and mutans streptococci levels. 36 to 60 month-old children were selected to participate in this study. Children were grouped into CF group (n=29), ECC group (n=25) and S-ECC group (n=29). Saliva was collected from children for microbiological analysis by culture. Salivary concentrations of cathelicidin LL-37, human β-defensin 2 (hBD-2), human β-defensin 3 (hBD-3) and histatin-5 (HTN-5) were determined by ELISA. Salivary concentrations of AMPs did not differ among CF, ECC and S-ECC groups. Data showed positive correlations between mutans streptococci levels and salivary hBD-2 or HTN-5. Positive correlations were found between hBD-2, hBD-3, LL-37 and HTN-5. Combinations among AMPs, mainly LL-37, were positively associated with caries levels. Salivary concentrations of AMPs individually were not associated with the severity of early childhood caries. The stimulus of caries appears to trigger a biological response, however, with a combination of these peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determination of a brass alloy concentration composition using calibration-free laser-induced breakdown spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Achouri, M.; Baba-Hamed, T.; Beldjilali, S. A., E-mail: sidahmed.beldjilali@univ-usto.dz

2015-09-15

Laser-induced breakdown spectroscopy (LIBS) is a technique that can provide qualitative and quantitative measurements of the characteristics of irradiated metals. In the present work, we have calculated the parameters of the plasma produced from a brass alloy sample under the action of a pulsed Nd: YAG laser operating at 1064 nm. The emission lines of copper atoms (Cu I), zinc atoms (Zn I), and lead atoms (Pb I), which are elements of a brass alloy composition, were used to investigate the parameters of the brass plasma. The spectral profiles of Cu, Zn, and Pb lines have been used to extractmore » the electron temperature and density of the brass alloy plasma. The characteristics of Cu, Zn, and Pb were determined quantatively by the calibration-free LIBS (CF-LIBS) method considering for accurate analysis that the laser-induced ablated plasma is optically thin in local thermodynamic equilibrium conditions and the plasma ablation is stoichiometric. The Boltzmann plot method was used to evaluate the plasma temperature, and the Stark broadened profiles were used to determine the electron density. An algorithm based on the experimentally measured values of the intensity of spectral lines and the basic laws of plasma physics was developed for the determination of Cu, Zn, and Pb concentrations in the brass sample. The concentrations C{sub CF-LIBS} calculated by CF-LIBS and the certified concentrations C{sub certified} were very close.« less

Several siblings with Cystic Fibrosis as a risk factor for poor outcome.

PubMed

Lavie, Moran; Shemer, Ofer; Sarouk, Ifat; Bar Aluma, Bat el; Dagan, Adi; Efrati, Ori; Vilozni, Daphna

2015-01-01

Occurrence of Cystic Fibrosis (CF) in more than one member in a family is not uncommon. The aim of our study was to assess the influence of multiple siblings with CF on disease expression and outcome. Study group consisted of 2-siblings (2-sibs, n = 42) or 3/4 siblings (3/4-sibs, n = 22) with CF in one family. Each sibling was matched by age, mutation, and gender to a single CF patient. 3/4-sibs subgroup compared to singles showed a lower mean FEV1 with a faster decline rate (58.4 ± 27.5 vs. 72.7 ± 25.4 and -5 ± 6.4 vs. -1.7 ± 2.8 %predicted decline/year respectively, p < .05), more airway colonization by Pseudomonas aeruginosa and Mycobacterium abscessus (15 (68%) vs. 8 (36%) and 7 (32%) vs. 4 (18%), respectively, p < .05) and more lung transplants (5 (23%) vs. 2 (9%), respectively, p < .02). Last mean FEV1 within 3/4-sibs was significantly lower for the youngest sib (p < .05). Three or more CF patients in one family may be a risk factor for more severe disease and poor prognosis. In our view this reflects the burden of disease on the patients and families. Copyright © 2014 Elsevier Ltd. All rights reserved.

Risk factors for totally implantable venous access device-associated complications in cystic fibrosis.

PubMed

McCarthy, C; O'Carroll, O; O'Brien, M E; McEnery, T; Franciosi, A; Gunaratnam, C; McElvaney, N G

2018-05-01

Candidaemia is an important nosocomial infection, seen frequently in immunocompromised and critically ill patients and increasingly recognised in cystic fibrosis (CF) patients with totally implantable venous access devices (TIVADs). This study aims to investigate the incidence and risk factors for the development of TIVAD-associated candidaemia and to assess the rate of TIVAD-related complications in CF patients. A 10-year retrospective study was carried out on adult CF patients attending a single centre. Complications were recorded including the incidence of candidaemia and correlated to clinical parameters. Complication rates were calculated based on incidence per 1000 catheter days. Statistical analysis was performed using Mann-Whitney U test and Fisher's exact test. Fourteen cases of candidaemia were observed in the CF cohort, primarily caused by Candida parapsilosis and Candida albicans. Candidaemia was associated with lower FEV1 (p = 0.0117) and higher frequency of pulmonary exacerbation (p < 0.0001). A TIVAD complication rate of 0.337/1000 catheter days was observed in the CF cohort. Complications included venous thrombosis, stenosis, and port extrusion; complications were independently associated with more frequent pulmonary exacerbations (p = 0.04). TIVAD complications are observed more commonly in those with lower FEV1 and frequent pulmonary exacerbations, suggesting that candidaemia may be related to antibiotic use and furthermore can occur following invasive procedures causing translocation of fungal species allowing transformation from colonisation to pathogenic infection.

Analyzing Fish Condition Factor Index Through Skew-Gaussian Information Theory Quantifiers

NASA Astrophysics Data System (ADS)

Contreras-Reyes, Javier E.

2016-06-01

Biological-fishery indicators have been widely studied. As such the condition factor (CF) index, which interprets the fatness level of a certain species based on length and weight, has been investigated, too. However, CF has been studied without considering its temporal features and distribution. In this paper, we analyze the CF time series via skew-gaussian distributions that consider the asymmetry produced by extreme events. This index is characterized by a threshold autoregressive model and corresponds to a stationary process depending on the shape parameter of the skew-gaussian distribution. Then we use the Jensen-Shannon (JS) distance to compare CF by length classes. This distance has mathematical advantages over other divergences such as Kullback-Leibler and Jeffrey’s, and the triangular inequality property. Our results are applied to a biological catalogue of anchovy (Engraulis ringens) from the northern coast of Chile, for the period 1990-2010 that consider monthly CF time series by length classes and sex. We find that for high values of shape parameter, JS distance tends to be more sensible to detect discrepancies than Jeffrey’s divergence. In addition, the body condition of male anchovies with higher lengths coincides with the ending of the moderate-strong El Niño event 91-92 and for both males and females, the smaller lengths coincide with the beginning of the strong El Niño event 97-98.

Enhanced electro-Fenton Mineralization of Acid Orange 7 Using a Carbon Nanotube Fiber Based Cathode

NASA Astrophysics Data System (ADS)

Huong Le, Thi Xuan; Alemán, Belén; Vilatela, Juan J.; Bechelany, Mikhael; Cretin, Marc

2018-02-01

A new cathodic material for electro-Fenton (EF) process was prepared based on a macroscopic fiber (CNTF) made of mm long carbon nanotubes directly spun from the gas phase by floating catalyst CVD, on a carbon fiber (CF) substrate. CNTF@CF electrode is a highly graphitic material combining a high surface area ( 260 m2/g) with high electrical conductivity and electrochemical stability . One kind of azo dye, acid orange 7 (AO7), was used as model bio-refractory pollutant to be treated at CNTF@CF cathode in acidic aqueous medium (pH 3.0). The experimental results pointed out that AO7 and its organic intermediate compounds were totally mineralized by hydroxyl radical generated from Fenton reaction. In fact, 96.7 % of the initial TOC was eliminated in 8h of electrolysis by applying a current of -25 mA and ferrous ions as catalyst at concentration of 0.2 mM. At the same electrolysis time, only 23.7 % of TOC removal found on CF support which proved the high mineralization efficiency of new material thanks to CNTs deposition. The CNTF@CF cathode maintained stable its activity during five experimental cycles of EF set-up. The results indicated that CNTF@CF material could be a potential choice for wastewater treatment containing bio-refractory by electrochemical advanced oxidation processes (EAOPs).

STELLAR CONTRIBUTION FUNCTIONS IN THE AGE OF CHEMICAL STRATIFICATION

NASA Astrophysics Data System (ADS)

Cowley, Charles; Sheminova, Valya; Castelli, Fiorella; Monier, Richard

2018-01-01

Contribution functions (CF's) were important tools to probe formation depths of features in the early numerical calculations of analytical stellar spectroscopy. In more recent work, CF's have played a minor role. Gray's (2005) text briefly discusses CF's, but CF's are not in Hubeny and Mihalas (2015). Gurtovenko and Sheminova (2015) give an extensive review of contribution functions in a recent preprint (arXiv:1505.00975). The realization that the atmospheres of certain stars are chemically stratified (Ryabchikova, Wade \\& LeBlanc, 2003, in IAU Symp. 210), and much subsequent work makes CF's of current interest. We employ new as well as older methods to compute CF's to find important layers, either for specific intensity or line depth for various points on the line profile. The most important layer is the one that causes the biggest change in the magnitude of the feature when the line absorption coefficient is set equal to zero for successive layers. This is readily done for a stratified or unstratified model. For an equivalent width, W, we calculate $(W-W_i/W) $, where $W_i$ is the equivalent width without absorption from the $i^th$ layer. We concentrate on cases where stratification is most obvious, for example, the Ca II K-line profile in the roAp stars and HR 6000 (Castelli, et al. 2017, A\\&A, 601, A119).

Serum Phospholipid Fatty Acid Composition in Cystic Fibrosis Patients with and without Liver Cirrhosis.

PubMed

Drzymała-Czyż, Sławomira; Szczepanik, Mariusz; Krzyżanowska, Patrycja; Duś-Żuchowska, Monika; Pogorzelski, Andrzej; Sapiejka, Ewa; Juszczak, Paweł; Lisowska, Aleksandra; Koletzko, Berthold; Walkowiak, Jarosław

2017-01-01

Cystic fibrosis (CF) liver disease is the third most frequent cause of death in CF patients. Although it alters fatty acid (FA) metabolism, data concerning the profile of FA in CF patients with liver cirrhosis is lacking. This study aimed to assess the FA composition of serum phospholipids in CF patients with and without liver cirrhosis. The study comprised 25 CF patients with liver cirrhosis and 25 without it. We assessed Z-scores for body height and weight, lung function, exocrine pancreatic sufficiency and colonization with Pseudomonas aeruginosa. FAs' profile of serum glycerophospholipids was quantified by gas chromatography mass spectrometry. In CF patients with liver cirrhosis, the levels of C16:0 were higher and the amounts of C20:2n-6, C20:3n-6, C20:4n-6, and all the n-3 polyunsaturated FAs (PUFAs) (C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3) were lower than those in CF subjects without liver cirrhosis. The n-6/n-3, C20:4n-6/C18:2n-6, total n-6/C18:2n-6, C20:5n-3/C18:3n-3 and total n-3/C18:3n-3 ratios did not differ between the 2 groups. Liver cirrhosis may associate with profound abnormalities in the composition of serum glycerophospholipids FAs in CF patients. None of the analyzed clinical factors could explain the greater prevalence of low levels of PUFAs in this CF subgroup. © 2017 S. Karger AG, Basel.

Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.

PubMed

Jain, Subheet K; Utreja, Puneet; Tiwary, Ashok K; Mahajan, Mohit; Kumar, Nikhil; Roy, Partha

2014-01-01

The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.

Developing new products in cystic fibrosis: needs and obstacles for activities of small and middle-sized companies.

PubMed

Schlangen, Miriam; Reimann, Andreas L G

2011-06-01

Small and middle-sized enterprises (SMEs) can make important contributions to medical progress through the development of new safe and effective drugs that address the greatest unmet needs of patients. Regulatory inconsistencies across agencies in various countries, however, remain major challenges in cystic fibrosis (CF) drug development. Clear and consistent treatment guidelines, well educated clinical trial sites, a patient registry and grant funding for early development programs are important success-factors for an efficient development process. SMEs developing products for CF need partners in the CF community to assist with disease education and awareness for ongoing clinical trials. SMEs should collaborate and communicate with the CF community in a legally compliant way to take a patient-centric approach to drug design, development and administration. Furthermore, they can help to develop educational tools and fund medical education activities to increase the understanding of the underlying defects and mechanisms of CF disease. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Effects of dietary exposure to herbicide and of the nutritive quality of contaminated food on the reproductive output of Daphnia magna.

PubMed

Bessa da Silva, M; Abrantes, N; Rocha-Santos, T A P; Duarte, A C; Freitas, A C; Gomes, A M; Carvalho, A P; Marques, J C; Gonçalves, F; Pereira, R

2016-10-01

Risk assessment of pesticides has been based on direct toxic effects on aquatic organisms. Indirect effects data are taken into account but with limitations, as it is frequently difficult to predict their real impacts in the ecosystems. In this context the main aim of this work was to assess how the exposure to the herbicide pendimethalin (Prowl(®)), under environmentally relevant concentrations, may compromise the nutritional composition of food for a relevant group of primary consumers of freshwater food webs-the daphnids, thus affecting their reproduction performance and subsequently the long-term sustainability of active populations of this grazer. Therefore, Daphnia magna individuals were chronically exposed in a clean medium to a control diet (NCF - i.e., non-contaminated green algae Raphidocelis subcapitata) and to a contaminated diet (CF - i.e., the same monoalgal culture grown in a medium enriched with pendimethalin in a concentration equivalent to the EC20 for growth inhibition of algae), during which reproductive endpoints were assessed. The algae were analysed for protein, carbohydrate and fatty acid content. The chemical composition of R. subcapitata in the CF revealed a slight decrease on total fatty acid levels, with a particular decrease of essential ω9 monounsaturated fatty acids. In contrast, the protein content was high in the CF. D. magna exposed to CF experienced a 16% reduction in reproduction, measured as the total number of offspring produced per female. Additionally, an internal pendimethalin body burden of 4.226μgg(-1) was accumulated by daphnids fed with CF. Hence, although it is difficult to discriminate the contribution of the pesticide (as a toxic agent transferred through the food web) from that of the food with a poor quality-compromised by the same pesticide, there are no doubts that, under environmentally relevant concentrations of pesticides, both pathways may compromise the populations of freshwater grazers in the long term, with consequences in the control of the primary productivity of these systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Oral bacteria--the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis.

PubMed

Zetterquist, Wilhelm; Marteus, Helena; Kalm-Stephens, Pia; Näs, Elisabeth; Nordvall, Lennart; Johannesson, Marie; Alving, Kjell

2009-02-01

Nitrite in exhaled breath condensate (EBC) has been shown to be elevated in cystic fibrosis (CF), while exhaled nitric oxide (FENO) is paradoxically low. This has been argued to reflect increased metabolism of NO while its diffusion is obstructed by mucus. However, we wanted to study the possible influence of salivary nitrite and bacterial nitrate reduction on these parameters in CF patients by the intervention of an anti-bacterial mouthwash. EBC and saliva were collected from 15 CF patients (10-43 years) and 15 controls (9-44 years) before and 5 min after a 30s chlorhexidine mouthwash, in parallel with measurements of FENO. Nitrite and nitrate concentrations were measured fluorometrically. EBC nitrite, but not nitrate, was significantly higher in the CF patients (median 3.6 vs 1.3 microM in controls, p<0.05) and decreased after mouthwash in both groups (3.6-1.4 microM, p<0.01; 1.3-0.5 microM, p<0.01). Salivary nitrite correlated significantly to EBC nitrite (r=0.60, p<0.001) and decreased correspondingly after chlorhexidine, whereas salivary nitrate increased. FENO was lower in CF and the difference between patients and controls was accentuated after mouthwash (5.4 vs 8.4 ppb in controls, p<0.05). EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.

Empirical Leucine-to-Carbon Conversion Factors for Estimating Heterotrophic Bacterial Production: Seasonality and Predictability in a Temperate Coastal Ecosystem▿

PubMed Central

Calvo-Díaz, Alejandra; Morán, Xosé Anxelu G.

2009-01-01

Leucine-to-carbon conversion factors (CFs) are needed for converting substrate incorporation into biomass production of heterotrophic bacteria. During 2006 we performed 20 dilution experiments for determining the spatiotemporal variability of empirical CFs in temperate Atlantic coastal waters. Values (0.49 to 1.92 kg C mol Leu−1) showed maxima in autumn to early winter and minima in summer. Spatially averaged CFs were significantly negatively correlated with in situ leucine incorporation rates (r = −0.91) and positively correlated with phosphate concentrations (r = 0.76). These relationships, together with a strong positive covariation between cell-specific leucine incorporation rates and carbon contents (r = 0.85), were interpreted as a strategy to maximize survival through protein synthesis and low growth rates under nutrient limitation (low CFs) until favorable conditions stimulate cell division relative to protein synthesis (high CFs). A multiple regression with in situ leucine incorporation rates and cellular carbon contents explained 96% of CF variance in our ecosystem, suggesting their potential prediction from more easily measurable routine variables. The use of the theoretical CF of 1.55 kg C mol Leu−1 would have resulted in a serious overestimation (73%) of annual bacterial production rates. Our results emphasize the need for considering the temporal scale in CFs for bacterial production studies. PMID:19304821

Neonatal Injury at Cephalic Vaginal Delivery: A Retrospective Analysis of Extent of Association with Shoulder Dystocia

PubMed Central

Iskender, Cantekin; Kaymak, Oktay; Erkenekli, Kudret; Ustunyurt, Emin; Uygur, Dilek; Yakut, Halil Ibrahim; Danisman, Nuri

2014-01-01

Purpose To describe the risk factors and labor characteristics of Clavicular fracture (CF) and brachial plexus injury (BPI); and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. Methods This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300) was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. Results During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2%) sustained permanent injury, whereas one neonate (4.5%) with BPI following shoulder dystocia sustained permanent injury (p = 0.34). Conclusion BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae. PMID:25144234

Macrophage Migration Inhibitory Factor Enzymatic Activity, Lung Inflammation, and Cystic Fibrosis

PubMed Central

Adamali, Huzaifa; Armstrong, Michelle E.; McLaughlin, Anne Marie; Cooke, Gordon; McKone, Edward; Costello, Christine M.; Gallagher, Charles G.; Leng, Lin; Baugh, John A.; Fingerle-Rowson, Günter; Bucala, Richard J.; McLoughlin, Paul

2012-01-01

Rationale: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury. Objectives: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF’s tautomerase activity in a murine model of Pseudomonas aeruginosa infection. Methods: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif+/+) and in tautomerase-null, MIF gene knockin mice (mif P1G/P1G). Measurements and Main Results: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mifP1G/P1G compared with mif+/+ mice. Conclusions: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine. PMID:22592805

GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

PubMed Central

Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

2013-01-01

Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

Fish pollution with anthropogenic 137Cs in the southern Baltic Sea.

PubMed

Zalewska, Tamara; Suplińska, Maria

2013-02-01

This paper presents the results of a study on changes in (137)Cs activity concentrations in three fish species from the southern Baltic Sea: cod (Gadus morhua), herring (Clupea harengus) and flounder (Platichtys flesus), in the period 2000-2010. During the study period a marked decline in cesium activity concentration in fish muscle tissue was observed, which reflected changes in radionuclide activity concentration in seawater. No statistically significant temporal trends were determined in changes of concentration factors (CF(fish/seawater)) calculated for the examined fish species. The analysis of (137)Cs activity as a function of ichthyological parameters revealed the lack of a relationship between radionuclide activity concentrations in herring muscle tissue and the fish age in an narrow age range (2-4 years). However, a reverse proportionality of total fish mass, as well as body length, against (137)Cs activity concentrations in muscles was well documented. The latter observation can be the direct result of the dilution effect related to the increase of fish body weight. (137)Cs activity concentration in muscle tissue of the five fish species forms a declining sequence: Gadus morhua, Platichthys flesus, Clupea harengus, Perca fluviatilis and Neogobius melanostomus. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Unimolecular Reactions of CF3CHF2 Studied by Chemical Activation: Assignment of Rate Constants and Threshold Energies to the 1,2-H Atom Transfer, 1,1-HF and 1,2-HF Elimination Reactions, and the Dependence of Threshold Energies on the Number of F-Atom Substituents in the Fluoroethane Molecules.

PubMed

Smith, Caleb A; Gillespie, Blanton R; Heard, George L; Setser, D W; Holmes, Bert E

2017-11-22

The recombination of CF 3 and CHF 2 radicals in a room-temperature bath gas was used to prepare vibrationally excited CF 3 CHF 2 * molecules with 101 kcal mol -1 of vibrational energy. The subsequent 1,2-H atom transfer and 1,1-HF and 1,2-HF elimination reactions were observed as a function of bath gas pressure by following the CHF 3 , CF 3 (F)C: and C 2 F 4 product concentrations by gas chromatography using a mass spectrometer as the detector. The singlet CF 3 (F)C: concentration was measured by trapping the carbene with trans-2-butene. The experimental rate constants are 3.6 × 10 4 , 4.7 × 10 4 , and 1.1 × 10 4 s -1 for the 1,2-H atom transfer and 1,1-HF and 1,2-HF elimination reactions, respectively. These experimental rate constants were matched to statistical RRKM calculated rate constants to assign threshold energies (E 0 ) of 88 ± 2, 88 ± 2, and 87 ± 2 kcal mol -1 to the three reactions. Pentafluoroethane is the only fluoroethane that has a competitive H atom transfer decomposition reaction, and it is the only example with 1,1-HF elimination being more important than 1,2-HF elimination. The trend of increasing threshold energies for both 1,1-HF and 1,2-HF processes with the number of F atoms in the fluoroethane molecule is summarized and investigated with electronic-structure calculations. Examination of the intrinsic reaction coordinate associated with the 1,1-HF elimination reaction found an adduct between CF 3 (F)C: and HF in the exit channel with a dissociation energy of ∼5 kcal mol -1 . Hydrogen-bonded complexes between HF and the H atom migration transition state of CH 3 (F)C: and the F atom migration transition state of CF 3 (F)C: also were found by the calculations. The role that these carbene-HF complexes could play in 1,1-HF elimination reactions is discussed.

Magnetic evidence for heavy metal pollution of topsoil in Shanghai, China

NASA Astrophysics Data System (ADS)

Wang, Guan; Liu, Yuan; Chen, Jiao; Ren, Feifan; Chen, Yuying; Ye, Fangzhou; Zhang, Weiguo

2018-03-01

This study presents the results obtained from magnetic susceptibility and heavy metal (Cu, Zn, Pb, and Cr) concentration measurements of soil profiles collected from arable land and urban parks in Baoshan District, an industrial district of Shanghai, China. The study focuses on the investigation of vertical variations in magnetic susceptibilities and heavy metal concentrations and on correlations between magnetic susceptibilities and heavy metal concentrations in soil profiles. The results demonstrate that magnetic enhancement in the surface layer of the soil profile is associated with increased heavy metal pollution. The enrichment factors (EF) and the Tomlinson Pollution Load Index (PLI-EF) are calculated for estimating the level of heavy metal pollution of soil profiles in the study. The significant positive correlations between heavy metal contents, enrichment factors (EF), Tomlinson pollution load index (PLI-CF), modified Tomlinson pollution load index (PLI-EF), and magnetic susceptibility (c) indicate that much of the heavy metal contamination in the study area is linked to combustion derived particulate emissions. The results confirm that the combined magnetic measurement and heavy metal concentration analysis could provide useful information for soil monitoring in urban environments. However, the use of magnetic technique to locate the heavy metal pollution boundary in the soil profile of this studied area should be confirmed by further geochemical analysis.

Confronting Compassion Fatigue: Assessment and Intervention in Inpatient Oncology
.

PubMed

Zajac, Lisa M; Moran, Katherine J; Groh, Carla J

2017-08-01

A notable variation among patient satisfaction scores with nursing care was identified. Contributing factors were examined and revealed significant negative correlations between the unit death rate and surviving patients' satisfaction scores. Compassion fatigue (CF) was hypothesized to be a major contributing factor.
. The objective was to address CF in RNs and oncology care associates (assistive personnel) by developing an intervention to provide bereavement support to staff after patient deaths.
. A mixed-methods sequential design was used. Instruments included the Professional Quality of Life scale and Press Ganey survey results. Univariate descriptive statistics, frequencies, an independent t test, and an analysis of covariance were used for data analysis.
. The preintervention results revealed average compassion satisfaction and secondary traumatic stress scores and low burnout scores. No significant difference was noted between pre- and postintervention CF scores. Patients' perception of nurses' skills improved significantly in the second quarter of 2015.

Accumulation and transport behaviour of 241americium, 60cobalt and 134cesium by eggs of the spotted dogfish Scyliorhinus canicula.

PubMed

Jeffree, Ross A; Oberhansli, Francois; Teyssie, Jean-Louis

2007-07-01

An experimental study examined the 96-h net influx from seawater of the anthropogenic radionuclides (241)Am, (60)Co and (134)Cs through the egg-case of the spotted dogfish Scyliorhinus canicula. Net influx directly through the wall of the egg-case was greatest for (134)Cs, then (241)Am and lastly (60)Co. Within the egg-case wall itself the measured concentration factors (CFs) and their gradients in the external, median and internal layers showed that for both (241)Am and (60)Co they were >10(3) in the external layer and declined by an order of magnitude in the interior layer. In contrast (134)Cs had a CF of only about three in the external layer which declined by a factor of 2 towards the two more internal layers of the egg-case. The egg-case apertures, that open within the prehatching stage of embryological development, significantly (P<0.05) increased the net influx of (241)Am and (60)Co to the interior of the egg-case, although their water concentrations were still lower than those in the labelled seawater bath. In contrast, the aperture did not increase the net influx of (134)Cs whose water concentrations equilibrated with those in seawater. Together these results indicate that the egg-case wall is very permeable to (134)Cs, representing little barrier to its movement, and hence consistent with the lack of importance of the aperture in determining its internal water concentrations in the egg-case. In contrast, (241)Am and (60)Co show much higher rates of accumulation by the egg-case, consistent with the measured reduced permeability of its wall, and therefore giving greater prominence to its aperture in the net transfer of these two radionuclides to the egg case's interior. The presence of the embryo within its egg-case did not significantly (P>0.05) affect the rates of influx of radioisotopes, with the exception of an interactive effect for (60)Co with the egg-case aperture (P<0.05). The CF of only (241)Am in the embryo itself relative to the external seawater concentration was significantly (P<0.05) enhanced by the presence of the aperture.

Choline supplementation alters some amino acid concentrations with no change in homocysteine in children with cystic fibrosis and pancreatic insufficiency.

PubMed

Alshaikh, Belal; Schall, Joan I; Maqbool, Asim; Mascarenhas, Maria; Bennett, Michael J; Stallings, Virginia A

2016-05-01

The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children aged 5 to 18 years with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB) or placebo with similar energy and fat content. Plasma amino acids were measured at baseline and 3 and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most participants. Alanine and cysteine were elevated in 24% and 36% of participants, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared with placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine, and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LYM-X-SORB did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI. Copyright © 2016 Elsevier Inc. All rights reserved.

Choline Supplementation Alters Some Amino Acid Concentrations with No Change in Homocysteine in Children with Cystic Fibrosis and Pancreatic Insufficiency

PubMed Central

Alshaikh, Belal; Schall, Joan I.; Maqbool, Asim; Mascarenhas, Maria; Bennett, Michael J.; Stallings, Virginia A.

2016-01-01

The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children, ages 5 to 18 years, with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB™, LXS) or placebo with similar calorie and fat content. Plasma amino acids were measured at baseline, 3, and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most subjects. Alanine and cysteine were elevated in 24% and 36% of subjects, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared to placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LXS did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI. PMID:27101760

Rare earth crystal field spectra as a probe of librational motions in BaY2F8 solid state laser crystals

NASA Astrophysics Data System (ADS)

Capelletti, R.; Baraldi, A.; Buffagni, E.; Magnani, N.; Mazzera, M.

2010-11-01

The fine structure (FS) accompanying a few lines, originated by crystal field (CF) transitions of rare earths (RE), as Er3+ and Tm3+, in BaY2F8 single crystals, is analyzed as a function of the RE3+ concentration (0.5÷20 at%) and temperature (9-300 K), by using high resolution (as fine as 0.02 cm-1) Fourier transform spectroscopy and linear dichroism measurements. The 9 K absorption spectra show that FS includes weak, narrow, and closely spaced (0.4÷0.8 cm-1) lines, covering a few cm-1 range on both sides of the narrowest among the CF lines. The FS increases by increasing the RE3+ concentration and vanishes at rather low temperature (40 and 60 K for Er3+ and Tm3+, respectively). The polarized light spectra confirm the association of a given set of FS lines to a specific CF line. The FS is ascribed to the simultaneous excitation of an electronic CF transition and of a local librational (or hindered rotation) mode of the RE3+-F- group. The attribution is supported 1) by specific features of the host matrix and guest rare earths, which allow some mobility of F- ions, and 2) by the spacing of the FS lines, which is in excellent agreement with the calculated RE3+-F- group rotational constant.

Measurements of concentrations of chlorofluoromethanes (CFMs) carbon dioxide and carbon isotope ratio in stratospheric and tropospheric air by grab-sampling systems

NASA Technical Reports Server (NTRS)

Itoh, T.; Kubo, H.; Honda, H.; Tominaga, T.; Makide, Y.; Yakohata, A.; Sakai, H.

1985-01-01

Measurements of concentrations of chlorofluoromethanes (CFMs), carbon dioxide and carbon isotope ratio in stratospheric and tropospheric air by grab-sampling systems are reported. The balloon-borne grab-sampling system has been launched from Sanriku Balloon Center three times since 1981. It consists of: (1) six sampling cylinders, (2) eight motor driven values, (3) control and monitor circuits, and (4) pressurized housing. Particular consideration is paid to the problem of contamination. Strict requirements are placed on the choice of materials and components, construction methods, cleaning techniques, vacuum integrity, and sampling procedures. An aluminum pressurized housing and a 4-m long inlet line are employed to prevent the sampling air from contamination by outgassing of sampling and control devices. The sampling is performed during the descent of the system. Vertical profiles of mixing ratios of CF2Cl2, CFCl3 and CH4 are given. Mixing ratios of CF2Cl2 and CFCl3 in the stratosphere do not show the discernible effect of the increase of those in the ground level background, and decrease with altitude. Decreasing rate of CFCl3 is larger than that of CF2Cl2. CH4 mixing ratio, on the other hand, shows diffusive equilibrium, as the photodissociation cross section of CH4 is small and concentrations of OH radical and 0(sup I D) are low.

Purification of the bacteriocin bavaricin MN and characterization of its mode of action against Listeria monocytogenes Scott A cells and lipid vesicles.

PubMed

Kaiser, A L; Montville, T J

1996-12-01

Bavaricin MN was purified from Lactobacillus sake culture supernatant 135-fold with a final yield of 11%. Sequence analysis revealed bavaricin MN to be a 42-amino-acid peptide having a molecular weight of 4,769 and a calculated pI of 10.0. Computer analysis indicated that the C-terminal region may form an alpha-helical structure with an amphipathic nature deemed important in the interaction of bacteriocins with biological membranes. Bavaricin MN rapidly depleted the membrane potential (delta p) of energized Listeria monocytogenes cells in a concentration-dependent fashion. At a bavaricin MN concentration of 9.0 micrograms/ml, the delta p decreased by 85%. Both the electrical potential (delta psi) and Z delta pH components of the delta p were depleted, and this depletion was not dependent on a threshold level of proton motive force. In addition to studying the effect of bavaricin MN on the delta p of vegetative cells, bavaricin MN-induced carboxyfluorescein (CF) efflux from L. monocytogenes-derived lipid vesicles was also characterized. Bavaricin MN-induced CF leakage was also concentration dependent with an optimum of pH 6.0. The rate of CF efflux was 63% greater in lipid vesicles in which a delta psi was generated compared with that in lipid vesicles in the absence of a delta psi.

Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot.

PubMed

Pasquier, Jennifer; Ramachandran, Vimal; Abu-Qaoud, Moh'd Rasheed; Thomas, Binitha; Benurwar, Manasi J; Chidiac, Omar; Hoarau-Véchot, Jessica; Robay, Amal; Fakhro, Khalid; Menzies, Robert A; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Malik, Rayaz A; Talal, Talal K; Najafi-Shoushtari, Seyed Hani; Rafii, Arash; Abi Khalil, Charbel

2018-06-05

Charcot foot (CF) is a rare complication of Type 2 diabetes (T2D). We assessed circulating miRNAs in 17 patients with T2D and acute CF (G1), 17 patients with T2D (G2) and equivalent neuropathy and 17 patients with T2D without neuropathy (G3) using the high-throughput miRNA expression profiling. 51 significantly deregulated miRNAs were identified in G1 versus G2, 37 in G1 versus G3 and 64 in G2 versus G3. Furthermore, we demonstrated that 16 miRNAs differentially expressed between G1 versus G2 could be involved in osteoclastic differentiation. Among them, eight are key factors involved in CF pathophysiology. Our data reveal that CF patients exhibit an altered expression profile of circulating miRNAs.

Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

PubMed

Kolpen, Mette; Kühl, Michael; Bjarnsholt, Thomas; Moser, Claus; Hansen, Christine Rønne; Liengaard, Lars; Kharazmi, Arsalan; Pressler, Tanja; Høiby, Niels; Jensen, Peter Østrup

2014-01-01

Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(-) and NO2(-) in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(-) decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.

A Survival Strategy for Pseudomonas aeruginosa That Uses Exopolysaccharides To Sequester and Store Iron To Stimulate Psl-Dependent Biofilm Formation

PubMed Central

Yu, Shan; Wei, Qing; Zhao, Tianhu; Guo, Yuan

2016-01-01

ABSTRACT Exopolysaccharide Psl is a critical biofilm matrix component in Pseudomonas aeruginosa, which forms a fiber-like matrix to enmesh bacterial communities. Iron is important for P. aeruginosa biofilm development, yet it is not clearly understood how iron contributes to biofilm development. Here, we showed that iron promoted biofilm formation via elevating Psl production in P. aeruginosa. The high level of iron stimulated the synthesis of Psl by reducing rhamnolipid biosynthesis and inhibiting the expression of AmrZ, a repressor of psl genes. Iron-stimulated Psl biosynthesis and biofilm formation held true in mucoid P. aeruginosa strains. Subsequent experiments indicated that iron bound with Psl in vitro and in biofilms, which suggested that Psl fibers functioned as an iron storage channel in P. aeruginosa biofilms. Moreover, among three matrix exopolysaccharides of P. aeruginosa, Psl is the only exopolysaccharide that can bind with both ferrous and ferric ion, yet with higher affinity for ferrous iron. Our data suggest a survival strategy of P. aeruginosa that uses exopolysaccharide to sequester and store iron to stimulate Psl-dependent biofilm formation. IMPORTANCE Pseudomonas aeruginosa is an environmental microorganism which is also an opportunistic pathogen that can cause severe infections in immunocompromised individuals. It is the predominant airway pathogen causing morbidity and mortality in individuals affected by the genetic disease cystic fibrosis (CF). Increased airway iron and biofilm formation have been proposed to be the potential factors involved in the persistence of P. aeruginosa in CF patients. Here, we showed that a high level of iron enhanced the production of the key biofilm matrix exopolysaccharide Psl to stimulate Psl-dependent biofilm formation. Our results not only make the link between biofilm formation and iron concentration in CF, but also could guide the administration or use of iron chelators to interfere with biofilm formation in P. aeruginosa in CF patients. Furthermore, our data also imply a survival strategy of P. aeruginosa under high-iron environmental conditions. PMID:27565622

Freshwater Sediment Characterization Factors of Copper Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Pu, Yubing; Laratte, Bertrand; Ionescu, Rodica Elena

2017-01-01

Wide use of engineered nanoparticles (ENPs) is likely to result in the eventually accumulation of ENPs in sediment. The benthic organisms living in sediments may suffer relatively high toxic effects of ENPs. This study has selected copper oxide nanoparticles (nano-CuO) as a research object. To consider the impacts of spatial heterogeneity on ENPs toxicity, the characterization factor (CF) derived from life cycle assessment (LCA) methodology is used as an indicator in this study. A nano-specific fate model has been used to calculate the freshwater sediment fate factor (FF) of nano-CuO. A literature survey of the nano-CuO toxicology values has been performed to calculate the effect factor (EF). Seventeen freshwater sediment CFs of nano-CuO are proposed as recommended values for subcontinental regions. The region most likely to be affected by nano-CuO is northern Australia (CF of 21.01·103 CTUe, comparative toxic units) and the least likely is northern Europe and northern Canada (CF of 8.55·103 CTUe). These sediment CFs for nano-CuO could be used in the future when evaluating the ecosystem impacts of products containing nano-CuO by LCA method.

Effects of the toxic benthic dinoflagellate Ostreopsis cf. ovata on fertilization and early development of the sea urchin Lytechinus variegatus.

PubMed

Neves, Raquel A F; Contins, Mariana; Nascimento, Silvia M

2018-04-01

Blooms of the benthic dinoflagellate Ostreopsis cf. ovata have been recorded with increasing frequency, intensity and geographic distribution. This dinoflagellate produces potent toxins that may cause mortality of marine invertebrates. Adults of sea urchins are commonly affected by O. cf. ovata exposure with evidence of spines loss and high mortality during periods of high dinoflagellate abundances. Here, we report on the effects of the toxic dinoflagellate O. cf. ovata on fertilization and early development of the sea urchin Lytechinus variegatus, a key ecological herbivore. Lytechinus variegatus eggs and sperm were experimentally exposed to different concentrations of Ostreopsis cf. ovata (4, 40, 400, and 4000 cells ml -1 ) to test the hypothesis that fertilization success, embryonic and larval development of the sea urchin are negatively affected by the toxic dinoflagellate even at low abundances. Reduced fertilization, developmental failures, embryo and larval mortality, and occurrence of abnormal offspring were evident after exposure to O. cf. ovata. Fertilization decreased when gametes were exposed to high O. cf. ovata abundances (400 and 4000 cells ml -1 ), but just the exposure to the highest abundance significantly reduced fertilization success. Sea urchin early development was affected by O. cf. ovata in a dose-dependent way, high dinoflagellate abundances fully inhibited the early development of L. variegatus. Ostreopsis cf. ovata significantly increased the mortality of sea urchin eggs and embryos in the first hours of exposure (∼1-3 h), regardless of dinoflagellate abundance. Abundances of 400 and 4000 O. cf. ovata cells ml -1 induced significantly higher mortality on sea urchin initial stages in the first hours, and no egg or embryo was found in these treatments after 18 h of incubation. The early echinopluteus larva was only reached in the control and in treatments with low Ostreopsis cf. ovata abundances (4 and 40 cells ml -1 ). The exposure to O. cf. ovata led to significantly higher occurrence of skeletal anomalies in the early larva of L. variegatus. Interactions of sea urchin gametes and Ostreopsis cells may naturally occur in coastal areas due to the match between O. cf. ovata blooms and L. variegatus reproductive period. Reduced larval density and increased larval abnormalities were observed even at low abundances (4 and 40 cells ml -1 ) frequently found in tropical environments all year round. The chronic exposure to O. cf. ovata could significantly impact larval fitness, thus compromising recruitment success, and highlight the negative effects of benthic HABs on sea urchin populations and its possible broader ecological implications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reference intervals and percentiles for carotid-femoral pulse wave velocity in a healthy population aged between 9 and 87 years.

PubMed

Diaz, Alejandro; Zócalo, Yanina; Bia, Daniel; Wray, Sandra; Fischer, Edmundo Cabrera

2018-04-01

There is little information regarding age-related reference intervals (RIs) of carotid-femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year-to-year percentile curves and body-height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9-87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age-related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age-specific (year-to-year) percentile curves that were defined using the standard normal distribution. Age-specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height-related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years. ©2018 Wiley Periodicals, Inc.

Exosome and Microvesicle-Enriched Fractions Isolated from Mesenchymal Stem Cells by Gradient Separation Showed Different Molecular Signatures and Functions on Renal Tubular Epithelial Cells.

PubMed

Collino, Federica; Pomatto, Margherita; Bruno, Stefania; Lindoso, Rafael Soares; Tapparo, Marta; Sicheng, Wen; Quesenberry, Peter; Camussi, Giovanni

2017-04-01

Several studies have suggested that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) may mediate MSC paracrine action on kidney regeneration. This activity has been, at least in part, ascribed to the transfer of proteins/transcription factors and different RNA species. Information on the RNA/protein content of different MSC EV subpopulations and the correlation with their biological activity is currently incomplete. The aim of this study was to evaluate the molecular composition and the functional properties on renal target cells of MSC EV sub-populations separated by gradient floatation. The results demonstrated heterogeneity in quantity and composition of MSC EVs. Two peaks of diameter were observed (90-110 and 170-190 nm). The distribution of exosomal markers and miRNAs evaluated in the twelve gradient fractions showed an enrichment in fractions with a flotation density of 1.08-1.14 g/mL. Based on this observation, we evaluated the biological activity on renal cell proliferation and apoptosis resistance of low (CF1), medium (CF2) and high (CF3) floatation density fractions. EVs derived from all fractions, were internalized by renal cells, CF1 and CF2 but not CF3 fraction stimulated significant cell proliferation. CF2 also inhibited apoptosis on renal tubular cells submitted to ischemia-reperfusion injury. Comparative miRNomic and proteomic profiles reveal a cluster of miRNAs and proteins common to all three fractions and an enrichment of selected molecules related to renal regeneration in CF2 fraction. In conclusion, the CF2 fraction enriched in exosomal markers was the most active on renal tubular cell proliferation and protection from apoptosis.

Dams, floodplain land use, and riparian forest conservation in the semiarid Upper Colorado River Basin, USA

USGS Publications Warehouse

Andersen, D.C.; Cooper, D.J.; Northcott, K.

2007-01-01

Land and water resource development can independently eliminate riparian plant communities, including Fremont cottonwood forest (CF), a major contributor to ecosystem structure and functioning in semiarid portions of the American Southwest. We tested whether floodplain development was linked to river regulation in the Upper Colorado River Basin (UCRB) by relating the extent of five developed land-cover categories as well as CF and other natural vegetation to catchment reservoir capacity, changes in total annual and annual peak discharge, and overall level of mainstem hydrologic alteration (small, moderate, or large) in 26 fourth-order subbasins. We also asked whether CF appeared to be in jeopardy at a regional level. We classified 51% of the 57,000 ha of alluvial floodplain examined along >2600 km of mainstem rivers as CF and 36% as developed. The proportion developed was unrelated to the level of mainstem hydrologic alteration. The proportion classified as CF was also independent of the level of hydrologic alteration, a result we attribute to confounding effects from development, the presence of time lags, and contrasting effects from flow alteration in different subbasins. Most CF (68% by area) had a sparse canopy (???5% cover), and stands with >50% canopy cover occupied <1% of the floodplain in 15 subbasins. We suggest that CF extent in the UCRB will decline markedly in the future, when the old trees on floodplains now disconnected from the river die and large areas change from CF to non-CF categories. Attention at a basinwide scale to the multiple factors affecting cottonwood patch dynamics is needed to assure conservation of these riparian forests. ?? 2007 Springer Science+Business Media, LLC.

Compressive force induces osteoclast differentiation via prostaglandin E(2) production in MC3T3-E1 cells.

PubMed

Sanuki, Rina; Shionome, Chieko; Kuwabara, Akiko; Mitsui, Narihiro; Koyama, Yuki; Suzuki, Naoto; Zhang, Fan; Shimizu, Noriyoshi; Maeno, Masao

2010-04-01

In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We previously showed that compressive force (CF) controls bone formation by stimulating the production of PGE(2) and Ep2 and/or Ep4 receptors in osteoblasts. The present study was undertaken to examine the effect of CF on the production of PGE(2), cyclooxygenase-2 (COX-2), macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) using osteoblastic MC3T3-E1 cells and to examine the indirect effect of CF on osteoclast differentiation using RAW264.7 cells as osteoclast precursors. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 3.0 g/cm(2)) for 24 hr, and PGE(2) production was determined using ELISA. The expression of COX-2, M-CSF, RANKL, and OPG genes and proteins was determined using real-time PCR and ELISA, respectively. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of RAW 264.7 cells cultured for 10 days with conditioned medium from CF-treated MC3T3-E1 cells and soluble RANKL. As CF increased, PGE(2) production and the expression of COX-2, M-CSF, and RANKL increased, whereas OPG expression decreased. The number of TRAP-positive cells increased as CF increased. Celecoxib, a specific inhibitor of COX-2, blocked the stimulatory effect of CF on TRAP staining and the production of PGE(2), M-CSF, RANKL, and OPG. These results suggest that CF induces osteoclast differentiation by increasing M-CSF production and decreasing OPG production via PGE(2) in osteoblasts.

Developing a model for cystic fibrosis sociomicrobiology based on antibiotic and environmental stress.

PubMed

Lopes, Susana Patrícia; Azevedo, Nuno Filipe; Pereira, Maria Olívia

2017-12-01

Cystic fibrosis (CF) infections are invariably biofilm-mediated and polymicrobial, being safe to assume that a myriad of factors affects the sociomicrobiology within the CF infection site and modulate the CF community dynamics, by shaping their social activities, overall functions, virulence, ultimately affecting disease outcome. This work aimed to assess changes in the dynamics (particularly on the microbial composition) of dual-/three-species biofilms involving CF-classical (Pseudomonas aeruginosa) and unusual species (Inquilinus limosus and Dolosigranulum pigrum), according to variable oxygen conditions and antibiotic exposure. Low fluctuations in biofilm compositions were observed across distinct oxygen environments, with dual-species biofilms exhibiting similar relative proportions and P. aeruginosa and/or D. pigrum populations dominating three-species consortia. Once exposed to antibiotics, biofilms displayed high resistance profiles, and microbial compositions, distributions, and microbial interactions significantly challenged. The antibiotic/oxygen environment supported such fluctuations, which enhanced for three-species communities. In conclusion, antibiotic therapy hugely disturbed CF communities' dynamics, inducing significant compositional changes on multispecies consortia. Clearly, multiple perturbations may disturb this dynamic, giving rise to various microbiological scenarios in vivo, and affecting disease phenotype. Therefore, an appreciation of the ecological/evolutionary nature within CF communities will be useful for the optimal use of current therapies and for newer breakthroughs on CF antibiotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Ultra-accurate collaborative information filtering via directed user similarity

NASA Astrophysics Data System (ADS)

Guo, Q.; Song, W.-J.; Liu, J.-G.

2014-07-01

A key challenge of the collaborative filtering (CF) information filtering is how to obtain the reliable and accurate results with the help of peers' recommendation. Since the similarities from small-degree users to large-degree users would be larger than the ones in opposite direction, the large-degree users' selections are recommended extensively by the traditional second-order CF algorithms. By considering the users' similarity direction and the second-order correlations to depress the influence of mainstream preferences, we present the directed second-order CF (HDCF) algorithm specifically to address the challenge of accuracy and diversity of the CF algorithm. The numerical results for two benchmark data sets, MovieLens and Netflix, show that the accuracy of the new algorithm outperforms the state-of-the-art CF algorithms. Comparing with the CF algorithm based on random walks proposed by Liu et al. (Int. J. Mod. Phys. C, 20 (2009) 285) the average ranking score could reach 0.0767 and 0.0402, which is enhanced by 27.3% and 19.1% for MovieLens and Netflix, respectively. In addition, the diversity, precision and recall are also enhanced greatly. Without relying on any context-specific information, tuning the similarity direction of CF algorithms could obtain accurate and diverse recommendations. This work suggests that the user similarity direction is an important factor to improve the personalized recommendation performance.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease.

PubMed

Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

2018-01-27

To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) ( P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Cracking process of Fe-26Cr-1Mo during low cycle corrosion fatigue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J.Q.; Li, J.; Wang, Z.F.

1994-12-01

The corrosion fatigue (CF) life has been divided classically into the initiation'' and propagation'' periods. Usually, the crack initiation process dominates the component lifetime under the low cycle CF condition because the crack propagates rapidly one initiated. Despite much work done on the research of the CF crack initiation mechanisms, however, a full understanding of crack initiation is still lacking. There are some limitations in explaining the CF crack initiation in an aqueous solution using the above four mechanisms individually. And, it is difficult to conduct experiments in which one mechanism along can be examined. Although CF is complicated, itmore » is possible to reproduce a specific experiment condition which will have the dominant factor affecting the CF crack initiation. Once the cracks initiate on the smooth metal surface, their coalescence, micropropagation and macropropagation will take place successively. The initiated cracks propagate first in the range of several grains, and the behavior of the microcrack propagation is different from that of macrocrack propagation. For Fe-26Cr-1Mo ferritic stainless steel, the fundamental research work of straining electrode has been done by many investigators, but the observation of the material surface at different deformation processes has not been reported. In the present study, the detailed observation of the cracking process of the material has been carried out in low cycle CF.« less

FOXO1 content is reduced in cystic fibrosis and increases with IGF-I treatment.

PubMed

Smerieri, Arianna; Montanini, Luisa; Maiuri, Luigi; Bernasconi, Sergio; Street, Maria E

2014-10-08

Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

Epidemiology of nontuberculous mycobacteria (NTM) amongst individuals with cystic fibrosis (CF).

PubMed

Viviani, Laura; Harrison, Michael J; Zolin, Anna; Haworth, Charles S; Floto, R Andres

2016-09-01

Infection by nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF) is often associated with significant morbidity. Limited, conflicting results are published regarding risk factors for pulmonary NTM disease. We analysed factors potentially associated with NTM in a large population of European patients with CF. We investigated associations between presence of NTM and various factors for patients registered in the European Cystic Fibrosis Society Patient Registry. 374 (2.75%) of 13,593 patients studied had at least one positive NTM culture within the study year. Age- and FEV1-adjusted odds of NTM infection was more than 2.5 times higher (95%CI: 1.79; 3.60) in patients infected by Stenotrophomonas maltophilia than in patients not infected (p<0.0001), 2.36 times higher (95%CI: 1.80;3.08) in patients with ABPA than without (p<0.0001), 1.79 times higher (95%CI: 1.34; 2.38) in patients who use bronchodilators than in patients who don't (p<0.0001), 1.49 times higher (95%CI: 1.18; 1.89) in patients who use inhaled antibiotics than in patients who don't (p=0.001), and 1.30 times higher (95%CI: 1.02; 1.66) in patients who use rhDNase than in patients who don't (p=0.032). NTM-positive cultures in individuals with CF are associated with distinct clinical variables. Improved data collection identifying risk factors for NTM infection will allow more focused screening strategies, and influence therapeutic choices and infection control measures in high-risk patients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Sample dilution and bacterial community composition influence empirical leucine-to-carbon conversion factors in surface waters of the world's oceans.

PubMed

Teira, Eva; Hernando-Morales, Víctor; Cornejo-Castillo, Francisco M; Alonso-Sáez, Laura; Sarmento, Hugo; Valencia-Vila, Joaquín; Serrano Catalá, Teresa; Hernández-Ruiz, Marta; Varela, Marta M; Ferrera, Isabel; Gutiérrez Morán, Xosé Anxelu; Gasol, Josep M

2015-12-01

The transformation of leucine incorporation rates to prokaryotic carbon production rates requires the use of either theoretical or empirically determined conversion factors. Empirical leucine-to-carbon conversion factors (eCFs) vary widely across environments, and little is known about their potential controlling factors. We conducted 10 surface seawater manipulation experiments across the world's oceans, where the growth of the natural prokaryotic assemblages was promoted by filtration (i.e., removal of grazers [F treatment]) or filtration combined with dilution (i.e., also relieving resource competition [FD treatment]). The impact of sunlight exposure was also evaluated in the FD treatments, and we did not find a significant effect on the eCFs. The eCFs varied from 0.09 to 1.47 kg C mol Leu(-1) and were significantly lower in the FD than in the F samples. Also, changes in bacterial community composition during the incubations, as assessed by automated ribosomal intergenic spacer analysis (ARISA), were more pronounced in the FD than in the F treatments, compared to unmanipulated controls. Thus, we discourage the common procedure of diluting samples (in addition to filtration) for eCF determination. The eCFs in the filtered treatment were negatively correlated with the initial chlorophyll a concentration, picocyanobacterial abundance (mostly Prochlorococcus), and the percentage of heterotrophic prokaryotes with high nucleic acid content (%HNA). The latter two variables explained 80% of the eCF variability in the F treatment, supporting the view that both Prochlorococcus and HNA prokaryotes incorporate leucine in substantial amounts, although this results in relatively low carbon production rates in the oligotrophic ocean. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Sample Dilution and Bacterial Community Composition Influence Empirical Leucine-to-Carbon Conversion Factors in Surface Waters of the World's Oceans

PubMed Central

Hernando-Morales, Víctor; Cornejo-Castillo, Francisco M.; Alonso-Sáez, Laura; Sarmento, Hugo; Valencia-Vila, Joaquín; Serrano Catalá, Teresa; Hernández-Ruiz, Marta; Varela, Marta M.; Ferrera, Isabel; Gutiérrez Morán, Xosé Anxelu; Gasol, Josep M.

2015-01-01

The transformation of leucine incorporation rates to prokaryotic carbon production rates requires the use of either theoretical or empirically determined conversion factors. Empirical leucine-to-carbon conversion factors (eCFs) vary widely across environments, and little is known about their potential controlling factors. We conducted 10 surface seawater manipulation experiments across the world's oceans, where the growth of the natural prokaryotic assemblages was promoted by filtration (i.e., removal of grazers [F treatment]) or filtration combined with dilution (i.e., also relieving resource competition [FD treatment]). The impact of sunlight exposure was also evaluated in the FD treatments, and we did not find a significant effect on the eCFs. The eCFs varied from 0.09 to 1.47 kg C mol Leu−1 and were significantly lower in the FD than in the F samples. Also, changes in bacterial community composition during the incubations, as assessed by automated ribosomal intergenic spacer analysis (ARISA), were more pronounced in the FD than in the F treatments, compared to unmanipulated controls. Thus, we discourage the common procedure of diluting samples (in addition to filtration) for eCF determination. The eCFs in the filtered treatment were negatively correlated with the initial chlorophyll a concentration, picocyanobacterial abundance (mostly Prochlorococcus), and the percentage of heterotrophic prokaryotes with high nucleic acid content (%HNA). The latter two variables explained 80% of the eCF variability in the F treatment, supporting the view that both Prochlorococcus and HNA prokaryotes incorporate leucine in substantial amounts, although this results in relatively low carbon production rates in the oligotrophic ocean. PMID:26407885

Dual core quantum dots for highly quantitative ratiometric detection of trypsin activity in cystic fibrosis patients

NASA Astrophysics Data System (ADS)

Castelló Serrano, Iván; Stoica, Georgiana; Matas Adams, Alba; Palomares, Emilio

2014-10-01

We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for recessive genetic diseases like human cystic fibrosis. In a screening program in which the goal is to detect disease and also the carrier status, early diagnosis could be of great help.We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for recessive genetic diseases like human cystic fibrosis. In a screening program in which the goal is to detect disease and also the carrier status, early diagnosis could be of great help. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03952a

Enterococcus faecalis Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer In Vivo.

PubMed

Hirt, Helmut; Greenwood-Quaintance, Kerryl E; Karau, Melissa J; Till, Lisa M; Kashyap, Purna C; Patel, Robin; Dunny, Gary M

2018-02-13

Cell-cell communication mediated by peptide pheromones (cCF10 [CF]) is essential for high-frequency plasmid transfer in vitro in Enterococcus faecalis To examine the role of pheromone signaling in vivo , we established either a CF-producing (CF+) recipient or a recipient producing a biologically inactive variant of CF (CF- recipient) in a germfree mouse model 3 days before donor inoculation and determined transfer frequencies of the pheromone-inducible plasmid pCF10. Plasmid transfer was detected in the upper and middle sections of the intestinal tract 5 h after donor inoculation and was highly efficient in the absence of antibiotic selection. The transconjugant/donor ratio reached a maximum level approaching 1 on day 4 in the upper intestinal tract. Plasmid transfer was significantly lower with the CF- recipient. While rescue of the CF- mating defect by coculture with CF+ recipients is easily accomplished in vitro , no extracellular complementation occurred in vivo This suggests that most pheromone signaling in the gut occurs between recipient and donor cells in very close proximity. Plasmid-bearing cells (donors plus transconjugants) steadily increased in the population from 0.1% after donor inoculation to about 10% at the conclusion of the experiments. This suggests a selective advantage of pCF10 carriage distinct from antibiotic resistance or bacteriocin production. Our results demonstrate that pheromone signaling is required for efficient pCF10 transfer in vivo In the absence of CF+ recipients, a low level of transfer to CF- recipients occurred in the gut. This may result from low-level host-mediated induction of the donors in the gastrointestinal (GI) tract, similar to that previously observed in serum. IMPORTANCE Horizontal gene transfer is a major factor in the biology of Enterococcus faecalis , an important nosocomial pathogen. Previous studies showing efficient conjugative plasmid transfer in the gastrointestinal (GI) tracts of experimental animals did not examine how the enterococcal sex pheromone response impacts the efficiency of transfer. Our study demonstrates for the first time pheromone-enhanced, high-frequency plasmid transfer of E. faecalis plasmid pCF10 in a mouse model in the absence of antibiotic or bacteriocin selection. Pheromone production by recipients dramatically increased plasmid transfer in germfree mice colonized initially with recipients, followed by donors. The presence of a coresident community of common gut microbes did not significantly reduce in vivo plasmid transfer between enterococcal donors and recipients. In mice colonized with enterococcal recipients, we detected plasmid transfer in the intestinal tract within 5 h of addition of donors, before transconjugants could be cultured from feces. Surprisingly, pCF10 carriage provided a competitive fitness advantage unrelated to antibiotic resistance or bacteriocin production. Copyright © 2018 Hirt et al.

Interaction Between Short-Term Heat Pretreatment and Avermectin On 2nd Instar Larvae of Diamondback Moth, Plutella Xylostella (Linn)

PubMed Central

Gu, Xiaojun; Tian, Sufen; Wang, Dehui; Gao, Fei

2009-01-01

Based on the cooperative virulence index (c.f.), the interaction effect between short-term heat pretreatment and avermectin on 2nd instar larvae of diamondback moth (DBM), Plutella xylostella (Linnaeus), was assessed. The results suggested that the interaction results between short-term heat pretreatment and avermectin on the tested insects varied with temperature level as well as its duration and avermectin concentration. Interaction between heat pretreatment at 30°C and avermectin mainly resulted in addition. Meanwhile, pretreatment at 35°C for 2 or 4 h could antagonize the toxicity of avermectin at lower concentrations, which indicated a hormetic effect occurred. The results indicate that cooperative virulence index (c.f.) may be adopted in hormetic effect assessment. PMID:19809544

Luminosity and redshift dependence of the covering factor of active galactic nuclei viewed with WISE and Sloan digital sky survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toba, Y.; Matsuhara, H.; Oyabu, S.

2014-06-10

In this work, we investigate the dependence of the covering factor (CF) of active galactic nuclei (AGNs) on the mid-infrared (MIR) luminosity and the redshift. We constructed 12 and 22 μm luminosity functions (LFs) at 0.006 ≤z ≤ 0.3 using Wide-field Infrared Survey Explorer (WISE) data. Combining the WISE catalog with Sloan Digital Sky Survey (SDSS) spectroscopic data, we selected 223,982 galaxies at 12 μm and 25,721 galaxies at 22 μm for spectroscopic classification. We then identified 16,355 AGNs at 12 μm and 4683 AGNs at 22 μm by their optical emission lines and cataloged classifications in the SDSS. Followingmore » that, we estimated the CF as the fraction of Type 2 AGN in all AGNs whose MIR emissions are dominated by the active nucleus (not their host galaxies) based on their MIR colors. We found that the CF decreased with increasing MIR luminosity, regardless of the choice of Type 2 AGN classification criteria, and the CF did not change significantly with redshift for z ≤ 0.2. Furthermore, we carried out various tests to determine the influence of selection bias and confirmed that similar dependences exist, even when taking these uncertainties into account. The luminosity dependence of the CF can be explained by the receding torus model, but the 'modified' receding torus model gives a slightly better fit, as suggested by Simpson.« less

Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

PubMed

Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

2018-03-10

Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

IMPACT OF PSEUDOMONAS AND STAPHYLOCOCCAL INFECTION ON INFLAMMATION AND CLINICAL STATUS IN YOUNG CHILDREN WITH CYSTIC FIBROSIS

PubMed Central

Sagel, Scott D.; Gibson, Ronald L.; Emerson, Julia; McNamara, Sharon; Burns, Jane L.; Wagener, Jeffrey S.; Ramsey, Bonnie W.

2009-01-01

Objectives To assess the effects of Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) infection on lower airway inflammation and clinical status in young children with cystic fibrosis (CF). Study design We studied 111 children < 6 years of age who had two Pa positive oropharyngeal cultures within 12 months. We examined bronchoalveolar lavage fluid (BALF) inflammatory markers (cell count, differential, IL-8, IL-6, neutrophil elastase), CF-related bacterial pathogens, exotoxin A serology, and clinical indicators of disease severity. Results Young children with CF with both upper and lower airway Pa infection had higher neutrophil counts, IL-8 and free neutrophil elastase levels, increased likelihood of positive exotoxin A titers, and lower Shwachman scores compared with those with positive upper airway cultures only. Sa was associated with increased lower airway inflammation and the presence of both Pa and Sa had an additive effect on concentrations of lower airway inflammatory markers. BALF markers of inflammation increased with numbers of different bacterial pathogens detected. Conclusions Young children with CF with upper and lower airway Pa infection have heightened endobronchial inflammation and poorer clinical status compared with children with only upper airway Pa infection. The independent and additive effects of Sa on inflammation support the importance of polymicrobial infection in early CF lung disease. PMID:18822427

Altered binding of /sup 125/I-labeled calmodulin to a 46. 5-kilodalton protein in skin fibroblasts cultured from patients with cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tallant, E.A.; Wallace, R.W.

1987-02-01

The levels of calmodulin and calmodulin-binding proteins have been determined in cultured skin fibroblasts from patients with cystic fibrosis (CF) and age- and sex-matched controls. Calmodulin ranged from 0.20 to 0.76 microgram/mg protein; there was no difference between calmodulin concentration in fibroblasts from CF patients and controls. Calmodulin-binding proteins of 230, 212, 204, 164, 139, 70, 59, 46.5, and 41 kD were identified. A protein with a mobility identical to the 59-kD calmodulin-binding protein was labeled by antiserum against calmodulin-dependent phosphatase. Although Ca/sup 2 +//calmodulin-dependent phosphatase activity was detected, there was no different in activity between control and CF fibroblastsmore » or in the level of phosphatase protein as determined by radioimmunoassay. Lower amounts of /sup 125/I-calmodulin were bound to the 46.5-kD calmodulin-binding protein in CF fibroblasts as compared with controls. The 46.5-kD calmodulin-binding protein may be reduced in CF fibroblasts or its structure may be altered resulting in a reduced binding capacity and/or affinity for calmodulin and perhaps reflecting, either directly or indirectly, the genetic defect responsible for cystic fibrosis.« less

Inhibitory effect of hot-water extract from dried fruit of Crataegus pinnatifida on low-density lipoprotein (LDL) oxidation in cell and cell-free systems.

PubMed

Chu, Chia-Yih; Lee, Miao-Jane; Liao, Chuen-Lan; Lin, Wea-Lung; Yin, Yu-Fang; Tseng, Tsui-Hwa

2003-12-17

The dried fruit of Crataegus pinnatifida, a local soft drink material and medical herb, was found to possess potential against oxidative stress. In the preliminary study, the antioxidant potential of a hot-water extract obtained from the dried fruit of C. pinnatifida (CF-H) was evaluated in terms of its capacity of quenching 1,1-diphenyl-2-picrylhydrazyl free radicals (EC(50) = 0.118 mg/mL). After content analysis, it was found that CF-H is mainly composed of polyphenols including flavonoids (6.9%), procyanidins (2.2%), (+)-catechin (0.5%), and (-)-epicatechin (0.2%). The antioxidative bioactivity of CF-H had been assess previously using the models of CuSO(4) as cell-free system and sodium nitroprusside (SNP) plus macrophage RAW 264.7 cells as cell system to induce human low-density lipoprotein oxidation. CF-H was found to inhibit relative electrophoretic mobility and thiobarbituric acid reactive substances at the concentration of 0.5-1.0 mg/mL in the cell-free system and at 0.01-0.10 mg/mL in the cell system. Furthermore, it was found that CF-H decreased the SNP-induced cell lipid peroxidation and reduced glutathione depletion.

Monitoring liver damage using hepatocyte-specific methylation markers in cell-free circulating DNA.

PubMed

Lehmann-Werman, Roni; Magenheim, Judith; Moss, Joshua; Neiman, Daniel; Abraham, Ofri; Piyanzin, Sheina; Zemmour, Hai; Fox, Ilana; Dor, Talya; Grompe, Markus; Landesberg, Giora; Loza, Bao-Li; Shaked, Abraham; Olthoff, Kim; Glaser, Benjamin; Shemer, Ruth; Dor, Yuval

2018-06-21

Liver damage is typically inferred from serum measurements of cytoplasmic liver enzymes. DNA molecules released from dying hepatocytes are an alternative biomarker, unexplored so far, potentially allowing for quantitative assessment of liver cell death. Here we describe a method for detecting acute hepatocyte death, based on quantification of circulating, cell-free DNA (cfDNA) fragments carrying hepatocyte-specific methylation patterns. We identified 3 genomic loci that are unmethylated specifically in hepatocytes, and used bisulfite conversion, PCR, and massively parallel sequencing to quantify the concentration of hepatocyte-derived DNA in mixed samples. Healthy donors had, on average, 30 hepatocyte genomes/ml plasma, reflective of basal cell turnover in the liver. We identified elevations of hepatocyte cfDNA in patients shortly after liver transplantation, during acute rejection of an established liver transplant, and also in healthy individuals after partial hepatectomy. Furthermore, patients with sepsis had high levels of hepatocyte cfDNA, which correlated with levels of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Duchenne muscular dystrophy patients, in which elevated AST and ALT derive from damaged muscle rather than liver, did not have elevated hepatocyte cfDNA. We conclude that measurements of hepatocyte-derived cfDNA can provide specific and sensitive information on hepatocyte death, for monitoring human liver dynamics, disease, and toxicity.

Physico-Chemical and Heavy Metal Profiles of Top Soils Sourced from Abandoned Lead-Zinc Mines at Enyigba, Ameri and Ameka Villages, Abakaliki District, Ebonyi State, South Eastern Nigeria

NASA Astrophysics Data System (ADS)

Osayande, D. A.; Azi, E. D.; Obayagbona, N.; Ovwasa, O. M.; Anegbe, B.

2016-12-01

Twenty (20) soil samples were collected from several abandoned old Pb - Zn mines located in Enyigba, Ameri, Ameka villages in the Abakaliki district of Ebonyi State, South-Eastern Nigeria. The soils were analyzed for Fe, Mn, Cu, Zn, Pb, Cd, Ni, Cr, V, pH, organic carbon and Electrical Conductivity using routine procedures. The physic-chemical analyses showed that pH values were generally low. The Electrical conductivity of the soils were high while organic carbon content in the soil was generally low. The heavy metal mean trend indicated that Pb (86) > Zn (64) > Cu (20) > Cd (15) > Ni (7) > Cr (6) > V (1). Fe and Mn values were also high. The variations observed for the heavy metal suggested both geogenic and anthropogenic activities were responsible for their distribution. Soil contamination was assessed on the basis of contamination factor (CF) and enrichment factor (EF). The CF values for the soil revealed moderate contamination for Ni, Cr, V, Zn and Mn, while Pb and Cd showed high contamination. The results of enrichment factor (EF) showed that using Fe concentration in the background value, Ni, Cr, V and Mn had moderate enrichment, Pb and Zn showed significant enrichment while Cd indicated high enrichment. The results of the principal component and cluster analyses showed that Zn, Cu, Cd, Pb metal originated from similar source but may have been significantly influenced by anthropogenic activities, while Ni, Cr, V were attributable to geogenic sources.

Analysis of linear energy transfers and quality factors of charged particles produced by spontaneous fission neutrons from 252Cf and 244Pu in the human body.

PubMed

Endo, Akira; Sato, Tatsuhiko

2013-04-01

Absorbed doses, linear energy transfers (LETs) and quality factors of secondary charged particles in organs and tissues, generated via the interactions of the spontaneous fission neutrons from (252)Cf and (244)Pu within the human body, were studied using the Particle and Heavy Ion Transport Code System (PHITS) coupled with the ICRP Reference Phantom. Both the absorbed doses and the quality factors in target organs generally decrease with increasing distance from the source organ. The analysis of LET distributions of secondary charged particles led to the identification of the relationship between LET spectra and target-source organ locations. A comparison between human body-averaged mean quality factors and fluence-averaged radiation weighting factors showed that the current numerical conventions for the radiation weighting factors of neutrons, updated in ICRP103, and the quality factors for internal exposure are valid.

Effects of Cloud Properties on PM2.5 Levels in the Southeastern United States

NASA Astrophysics Data System (ADS)

Yu, C.; Zhang, X.; Liu, Y.

2012-12-01

The spatial and temporal characteristics of fine particulate matter (PM2.5) are increasingly being derived from satellite aerosol remote sensing data. A major concern of satellite-derived PM2.5 information is cloud cover, i.e., PM2.5 mass concentrations cannot be estimated from satellite observations under cloudy conditions. There has been little research on the effects of cloud properties on PM2.5 levels. In this study, we performed a statistical analysis of relationships between various cloud parameters and PM2.5 concentrations. We used 2005-2010 PM2.5 observations from 8 sites in the Southeastern Aerosol Research and Characterization (SEARCH) Network, and cloud parameters from MODIS cloud product retrievals from Terra and Aqua satellites. We find that cloud fraction (CF) is generally negatively correlated with the mean value of PM2.5 mass concentration. However, the largest mean value occurs when the cloud fraction is between 10% and 30% instead of lower cloud cover (CF < 10%). The mean value of PM2.5 decreased from 14.3μg/m3 during 10%~30% cloud fraction to 9.3μg/m3 in cloudy days (CF=100%), and the negative correlation is more significant during the summer and fall than spring and winter. In addition, Cloud top pressure (CTP) and cloud optical thickness (COT) also influence PM2.5 mass concentration, with CTP being positively correlated with PM2.5 while COT being negatively correlated. These results suggest that cloud parameters may be used as predictor variables in satellite models of PM2.5.

A baseline study on the concentration of trace elements in the surface sediments off Southwest coast of Tamil Nadu, India.

PubMed

Godson, Prince S; Magesh, N S; Peter, T Simon; Chandrasekar, N; Krishnakumar, S; Vincent, Salom Gnana Thanga

2018-01-01

Forty two surface sediment samples were collected in order to document baseline elemental concentration along the Southwest coast of Tamil Nadu, India. The elements detected were Manganese (Mn), Zinc (Zn), Iron (Fe), Copper (Cu), Nickel (Ni) and Lead (Pb). The concentration of Fe and Mn was primarily controlled by the riverine input. The source of Pb and Zn is attributed to leaded petrol and anti-biofouling paints. The calculated index (EF, Igeo and CF) suggests that the sediments of the study area are significantly enriched with all elements except Pb. The contamination factor showed the order of Mn>Zn>Fe>Cu>Ni>Pb. The sediment pollution index (SPI) revealed that the sediments belonged to low polluted to dangerous category. The correlation matrix and dendrogram showed that the elemental distribution was chiefly controlled by riverine input as well as anthropogenic activity in the coast. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lysobacter chengduensis sp. nov. Isolated from the Air of Captive Ailuropoda melanoleuca Enclosures in Chengdu, China.

PubMed

Wen, Caifang; Xi, Lixin; She, Rong; Zhao, Shan; Hao, Zhongxiang; Luo, Lu; Liao, Hong; Chen, Zhenrong; Han, Guoquan; Cao, Sanjie; Wu, Rui; Yan, Qigui; Hou, Rong

2016-01-01

A novel bacterial strain, designated as CF21(T), was isolated from the air of Ailuropoda melanoleuca enclosures in China. Cells were gram-negative, aerobic, non-motile, and rod shaped. Strain CF21(T) grew at 10-40 °C (optimum 28-30 °C) and pH 6.0-9.0 (optimum pH 7.0-8.0) and in the presence of NaCl concentrations ranging from 0.0% (w/v) to 2.0 % (optimum 0.0-1.0%). 16SrRNA gene sequence analysis indicated that strain CF21(T) belonged to genus Lysobacter within class Gammaproteobacteria and was most closely related to Luteimonas dalianensi OB44-3(T) (95.8% similarity), Lysobacter ruishenii CTN-1(T) (95.1%), Lysobacter spongiicola KMM329(T) (94.8 %), and Lysobacter daejeonensis GH1-9T (94.6%). The genomic G+C DNA content was 68.72 mol%. Major cellular fatty acids of CF21(T) were iso-C16:0 (30.22%), iso-C15:0 (25.70%), and the sum of 10-methyl C16 : 0 and/or iso-C17 : 1ω9c (21.94%). The prominent isoprenoid quinone was ubiquinone 8 (Q-8). Primary polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and an unknown phospholipid. DNA sequence relatedness between strain CF21(T) and L. ruishenii CTN-1(T) was 56%, which was clearly below the 70% threshold for prokaryotic species delineation. These analyses indicated that CF21(T) is a novel member of genus Lysobacter, for which the name Lysobacter chengduensis sp. nov. is proposed. The type strain is CF21(T) (=CGMCC1.15145(T) = DSM 100306(T)).

Cobalt Ferrite Bearing Nitrogen-Doped Reduced Graphene Oxide Layers Spatially Separated with Microporous Carbon as Efficient Oxygen Reduction Electrocatalyst.

PubMed

Kashyap, Varchaswal; Singh, Santosh K; Kurungot, Sreekumar

2016-08-17

The present work discloses how high-quality dispersion of fine particles of cobalt ferrite (CF) could be attained on nitrogen-doped reduced graphene oxide (CF/N-rGO) and how this material in association with a microporous carbon phase could deliver significantly enhanced activity toward electrochemical oxygen reduction reaction (ORR). Our study indicates that the microporous carbon phase plays a critical role in spatially separating the layers of CF/N-rGO and in creating a favorable atmosphere to ensure the seamless distribution of the reactants to the active sites located on CF/N-rGO. In terms of the ORR current density, the heat-treated hybrid catalyst at 150 °C (CF/N-rGO-150) is found to be clearly outperforming (7.4 ± 0.5 mA/cm(2)) the state-of-the-art 20 wt % Pt-supported carbon catalyst (PtC) (5.4 ± 0.5 mA/cm(2)). The mass activity and stability of CF-N-rGO-150 are distinctly superior to PtC even after 5000 electrochemical cycles. As a realistic system level exploration of the catalyst, testing of a primary zinc-air battery could be demonstrated using CF/N-rGO-150 as the cathode catalyst. The battery is giving a galvanostatic discharge time of 15 h at a discharge current density of 20 mA/cm(2) and a specific capacity of ∼630 mAh g(-1) in 6 M KOH by using a Zn foil as the anode. Distinctly, the battery performance of this system is found to be superior to that of PtC in less concentrated KOH solution as the electrolyte.

Invited Article: In situ comparison of passive radon-thoron discriminative monitors at subsurface workplaces in Hungary

NASA Astrophysics Data System (ADS)

Kávási, Norbert; Vigh, Tamás; Németh, Csaba; Ishikawa, Tetsuo; Omori, Yasutaka; Janik, Miroslaw; Yonehara, Hidenori

2014-02-01

During a one-year long measurement period, radon and thoron data obtained by two different passive radon-thoron discriminative monitors were compared at subsurface workplaces in Hungary, such as mines (bauxite and manganese ore) and caves (medical and touristic). These workplaces have special environmental conditions, such as, stable and high relative humidity (100%), relatively stable temperature (12°C-21°C), low or high wind speed (max. 2.4 m s-1) and low or elevated aerosol concentration (130-60 000 particles m-3). The measured radon and thoron concentrations fluctuated in a wide range among the different workplaces. The respective annual average radon concentrations and their standard deviations (in brackets) measured by the passive radon-thoron discriminative monitor with cellulose filter (CF) and the passive radon-thoron discriminative monitor with sponge filter (SF) were: 350(321) Bq m-3 and 550(497) Bq m-3 in the bauxite mine; 887(604) Bq m-3 and 1258(788) Bq m-3 in the manganese ore mine; 2510(2341) Bq m-3 and 3403(3075) Bq m-3 in the medical cave (Hospital Cave of Tapolca); and 6239(2057) Bq m-3 and 8512(1955) Bq m-3 in the touristic cave (Lake Cave of Tapolca). The respective average thoron concentrations and their standard deviation (in brackets) measured by CF and SF monitors were: 154(210) Bq m-3 and 161(148) Bq m-3 in the bauxite mine; 187(191) Bq m-3 and 117(147) Bq m-3 in the manganese-ore mine; 360(524) Bq m-3 and 371(789) Bq m-3 in the medical cave (Hospital Cave of Tapolca); and 1420(1184) Bq m-3 and 1462(3655) Bq m-3 in the touristic cave (Lake Cave of Tapolca). Under these circumstances, comparison of the radon data for the SF and CF monitors showed the former were consistently 51% higher in the bauxite mine, 38% higher in the manganese ore mine, and 34% higher in the caves. Consequently, correction is required on previously obtained radon data acquired by CF monitors at subsurface workplaces to gain comparable data for SF monitors. In the case of thoron, the data were unreliable and no significant tendency was seen during the comparison therefore comparison of previously obtained thoron data acquired by either CF or SF is doubtful. There was probable influence by relative humidity on the detection response; however, the effects of the high wind speed and elevated aerosol concentration could not be excluded. The results of this study call attention to the importance of calibration under extreme environmental conditions and the need for using reliable radon-thoron monitors for subsurface workplaces.

Heavy metal assessment in surface sediments off Coromandel Coast of India: Implication on marine pollution.

PubMed

N, Anbuselvan; D, Senthil Nathan; M, Sridharan

2018-06-01

The present study investigates the distribution of heavy metals (Fe, Cd, Co, Cr, Cu, Ni, Zn and Pb) in the surface sediments along the Coromandel Coast of Bay of Bengal as an indicator of marine pollution. Pollution indices such as Contamination factor (CF), Enrichment factor (EF) and Geo-accumulation index (I) were performed to assess the spatial distribution and pollution status of the study area. The heavy metal concentration in the study area is closely associated with grain size and organic matter. Both geoaccumulation index and metal contamination factor indicate that the sediments are free from contamination with regards to the metals Cr and Ni, followed by uncontamination to moderate contamination of Co, Cu and Zn. However, sediments are found to be extremely polluted with respect to Cd and Pb. Factor analysis reveals that the accumulation of these heavy metals in the shelf sediments are due to anthropogenic inputs from the adjacent land area. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diabetes in Cystic Fibrosis: Multicenter Screening Results Based on Current Guidelines

PubMed Central

Scheuing, Nicole; Holl, Reinhard W.; Dockter, Gerd; Fink, Katharina; Junge, Sibylle; Naehrlich, Lutz; Smaczny, Christina; Staab, Doris; Thalhammer, Gabriela; van Koningsbruggen-Rietschel, Silke; Ballmann, Manfred

2013-01-01

Background Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT). Methods Between 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight. Results At baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23–10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22–3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11–1.71]) and IFG+IGT (1.43 [1.11–1.83]), and in males also for DGT (1.49 [1.09–2.04]). Conclusions/Significance If confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD. PMID:24324701

Ammonia volatilization from a Chinese cabbage field under different nitrogen treatments in the Taihu Lake Basin, China.

PubMed

Shan, Linan; He, Yunfeng; Chen, Jie; Huang, Qian; Wang, Hongcai

2015-12-01

Ammonia (NH3) volatilization is a major pathway of nitrogen (N) loss from soil-crop systems. As vegetable cultivation is one of the most important agricultural land uses worldwide, a deeper understanding of NH3 volatilization is necessary in vegetable production systems. We therefore conducted a 3-year (2010-2012) field experiment to characterize NH3 volatilization and evaluate the effect of different N fertilizer treatments on this process during the growth period of Chinese cabbage. Ammonia volatilization rate, rainfall, soil water content, pH, and soil NH4(+) were measured during the growth period. The results showed that NH3 volatilization was significantly and positively correlated to topsoil pH and NH4(+) concentration. Climate factors and fertilization method also significantly affected NH3 volatilization. Specifically, organic fertilizer (OF) increased NH3 volatilization by 11.77%-18.46%, compared to conventional fertilizer (CF, urea), while organic-inorganic compound fertilizer (OIF) reduced NH3 volatilization by 8.82%-12.67% compared to CF. Furthermore, slow-release fertilizers had significantly positive effects on controlling NH3 volatilization, with a 60.73%-68.80% reduction for sulfur-coated urea (SCU), a 71.85%-78.97% reduction for biological Carbon Power® urea (BCU), and a 77.66%-83.12% reduction for bulk-blend controlled-release fertilizer (BBCRF) relative to CF. This study provides much needed baseline information, which will help in fertilizer choice and management practices to reduce NH3 volatilization and encourage the development of new strategies for vegetable planting. Copyright © 2015. Published by Elsevier B.V.

An adaptive beamforming method for ultrasound imaging based on the mean-to-standard-deviation factor.

PubMed

Wang, Yuanguo; Zheng, Chichao; Peng, Hu; Chen, Qiang

2018-06-12

The beamforming performance has a large impact on image quality in ultrasound imaging. Previously, several adaptive weighting factors including coherence factor (CF) and generalized coherence factor (GCF) have been proposed to improved image resolution and contrast. In this paper, we propose a new adaptive weighting factor for ultrasound imaging, which is called signal mean-to-standard-deviation factor (SMSF). SMSF is defined as the mean-to-standard-deviation of the aperture data and is used to weight the output of delay-and-sum (DAS) beamformer before image formation. Moreover, we develop a robust SMSF (RSMSF) by extending the SMSF to the spatial frequency domain using an altered spectrum of the aperture data. In addition, a square neighborhood average is applied on the RSMSF to offer a more smoothed square neighborhood RSMSF (SN-RSMSF) value. We compared our methods with DAS, CF, and GCF using simulated and experimental synthetic aperture data sets. The quantitative results show that SMSF results in an 82% lower full width at half-maximum (FWHM) but a 12% lower contrast ratio (CR) compared with CF. Moreover, the SN-RSMSF leads to 15% and 10% improvement, on average, in FWHM and CR compared with GCF while maintaining the speckle quality. This demonstrates that the proposed methods can effectively improve the image resolution and contrast. Copyright © 2018 Elsevier B.V. All rights reserved.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

PubMed Central

Maselli, Diego J.; Keyt, Holly; Restrepo, Marcos I.

2017-01-01

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases. PMID:28509852

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

PubMed

Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

2013-01-01

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. © 2013 Published by Elsevier Ltd.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.

PubMed

Maselli, Diego J; Keyt, Holly; Restrepo, Marcos I

2017-05-16

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa , Methicillin-resistant Staphylococcus aureus , Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

Stimulated Raman spectroscopy of 13CF4

NASA Astrophysics Data System (ADS)

Martínez, R. Z.; Bermejo, D.; Boudon, V.

2018-06-01

CF4 is a powerful greenhouse gas, mostly released in the atmosphere by industries. A careful modeling of its absorption spectrum is required in order to allow accurate atmospheric concentration measurements. For this aim, high resolution Raman spectroscopy is of great help, since it gives access to rovibrational levels that are not directly reachable through dipolar absorption, although they are involved in hot band generation. Following our previous work on 12CF4, we present here a similar investigation of the second isotopologue, 13CF4. The spectra of the ν1 (909.21 cm-1), 2ν1 -ν1 (906.77 cm-1), ν1 +ν2 -ν2 (909.33 cm-1), ν2 (435.47 cm-1), 2ν2 (868.10 cm-1) and 3ν2 -ν2 (865.73 cm-1) bands were obtained with a quasi-continuous wave stimulated Raman spectrometer. These six bands were studied at temperatures of 140 and 298 K (for the hot bands). These spectra could be assigned and modeled thanks to the XTDS and SPVIEW software developed in the Dijon group.

Slurry Erosive Wear Evaluation of HVOF-Spray Cr2O3 Coating on Some Turbine Steels

NASA Astrophysics Data System (ADS)

Goyal, Deepak Kumar; Singh, Harpreet; Kumar, Harmesh; Sahni, Varinder

2012-09-01

In this study, Cr2O3 coatings were deposited on CF8M and CA6NM turbine steels by high-velocity oxy-fuel (HVOF)-spray process and analyzed with regard to their performance under slurry erosion conditions. High Speed Erosion Test Rig was used for slurry erosion tests, and the effects of three parameters, namely, average particle size, speed (rpm), and slurry concentration on slurry erosion of these materials were investigated. SEM micrographs on the surface of samples, before and after slurry erosion tests, were taken to study the erosion mechanism. For the uncoated steels, CA6NM steel showed better erosion resistance in comparison with CF8M steel. The HVOF-sprayed Cr2O3-coated CF8M and CA6NM steels showed better slurry erosion resistance in comparison with their uncoated counterparts. It may be due to the higher hardness as a result of HVOF-sprayed Cr2O3 coating in comparison with the uncoated CF8M and CA6NM steels.

Cystic fibrosis Δf508 mutation screening in Brazilian women with altered fertility.

PubMed

Brunoro, G V F; Wolfgramm, E V; Louro, I D; Degasperi, I I; Busatto, V C W; Perrone, A M S; Batitucci, M C P

2011-10-01

Cystic Fibrosis (CF) is an autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator gene (CFTR). The most frequent mutation in CF is ΔF508. The disease is clinically characterized by elevated concentrations of sweat chlorides and abnormally thick mucus. It affects organs such as lung, pancreas, gastrointestinal and reproductive tract. Women with CF commonly present delayed puberty and amenorrhea due to malnutrition. Our objective was to screen the presence of ΔF508 mutation in 24 women with altered fertility. Nine of these women presented reduced fertility without a known cause, four showed polycystic ovaries and two had early menopause. One woman with early menopause was a carrier of the ΔF508 mutation. Our study demonstrates that it is possible that the frequency of CF mutations among patients with altered fertility may be higher than expected. Previous data showed that fibrocystic women can show reduced fertility, maternal mortality associated with pregnancy and increased incidence of spontaneous abortion. We therefore recommend that women with reduced fertility undertake genetic tests for a better evaluation of pregnancy risks and clinical monitoring.

Culture growth of testate amoebae under different silicon concentrations.

PubMed

Wanner, Manfred; Seidl-Lampa, Barbara; Höhn, Axel; Puppe, Daniel; Meisterfeld, Ralf; Sommer, Michael

2016-10-01

Testate amoebae with self-secreted siliceous shell platelets ("idiosomes") play an important role in terrestrial silicon (Si) cycles. In this context, Si-dependent culture growth dynamics of idiosomic testate amoebae are of interest. Clonal cultures of idiosomic testate amoebae were analyzed under three different Si concentrations: low (50μmolL -1 ), moderate/site-specific (150μmolL -1 ) and high Si supply (500μmolL -1 ). Food (Saccharomyces cerevisiae) was provided in surplus. (i) Shell size of four different clones of idiosomic testate amoebae either decreased (Trinema galeata, Euglypha filifera cf.), increased (E. rotunda cf.), or did not change (E. rotunda) under the lowest Si concentration (50μmolSiL -1 ). (ii) Culture growth of idiosomic Euglypha rotunda was dependent on Si concentration. The more Si available in the culture medium, the earlier the entry into exponential growth phase. (iii) Culture growth of idiosomic Euglypha rotunda was dependent on origin of inoculum. Amoebae previously cultured under a moderate Si concentration revealed highest sustainability in consecutive cultures. Amoebae derived from cultures with high Si concentrations showed rapid culture growth which finished early in consecutive cultures. (iv) Si (diluted in the culture medium) was absorbed by amoebae and fixed in the amoeba shells resulting in decreased Si concentrations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Glutamate transporter EAAT4 in Purkinje cells controls intersynaptic diffusion of climbing fiber transmitter mediating inhibition of GABA release from interneurons.

PubMed

Satake, Shin'ichiro; Song, Si-Young; Konishi, Shiro; Imoto, Keiji

2010-12-01

Neurotransmitters diffuse out of the synaptic cleft and act on adjacent synapses to exert concerted control of the synaptic strength within neural pathways that converge on single target neurons. The excitatory transmitter released from climbing fibers (CFs), presumably glutamate, is shown to inhibit γ-aminobutyric acid (GABA) release at basket cell (BC)-Purkinje cell (PC) synapses in the rat cerebellar cortex through its extrasynaptic diffusion and activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on BC axon terminals. This study aimed at examining how the CF transmitter-diffusion-mediated presynaptic inhibition is controlled by glutamate transporters. Pharmacological blockade of the PC-selective neuronal transporter EAAT4 markedly enhanced CF-induced inhibition of GABAergic transmission. Tetanic CF-stimulation elicited long-term potentiation of glutamate transporters in PCs, and thereby attenuated the CF-induced inhibition. Combined use of electrophysiology and immunohistochemistry revealed a significant inverse relationship between the level of EAAT4 expression and the inhibitory action of CF-stimulation on the GABA release at different cerebellar lobules - the CF-induced inhibition was profound in lobule III, where the EAAT4 expression level was low, whereas it was minimal in lobule X, where EAAT4 was abundant. The findings clearly demonstrate that the neuronal glutamate transporter EAAT4 in PCs plays a critical role in the extrasynaptic diffusion of CF transmitter - it appears not only to retrogradely determine the degree of CF-mediated inhibition of GABAergic inputs to the PC by controlling the glutamate concentration for intersynaptic diffusion, but also regulate synaptic information processing in the cerebellar cortex depending on its differential regional distribution as well as use-dependent plasticity of uptake efficacy. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Elevated Incidence of Dental Caries in a Mouse Model of Cystic Fibrosis

PubMed Central

Catalán, Marcelo A.; Scott-Anne, Kathleen; Klein, Marlise I.; Koo, Hyun; Bowen, William H.; Melvin, James E.

2011-01-01

Background Dental caries is the single most prevalent and costly infectious disease worldwide, affecting more than 90% of the population in the U.S. The development of dental cavities requires the colonization of the tooth surface by acid-producing bacteria, such as Streptococcus mutans. Saliva bicarbonate constitutes the main buffering system which neutralizes the pH fall generated by the plaque bacteria during sugar metabolism. We found that the saliva pH is severely decreased in a mouse model of cystic fibrosis disease (CF). Given the close relationship between pH and caries development, we hypothesized that caries incidence might be elevated in the mouse CF model. Methodology/Principal Findings We induced carious lesions in CF and wildtype mice by infecting their oral cavity with S. mutans, a well-studied cariogenic bacterium. After infection, the mice were fed a high-sucrose diet for 5 weeks (diet 2000). The mice were then euthanized and their jaws removed for caries scoring and bacterial counting. A dramatic increase in caries and severity of lesions scores were apparent in CF mice compared to their wildtype littermates. The elevated incidence of carious lesions correlated with a striking increase in the S. mutans viable population in dental plaque (20-fold increase in CF vs. wildtype mice; p value<0.003; t test). We also found that the pilocarpine-stimulated saliva bicarbonate concentration was significantly reduced in CF mice (16±2 mM vs. 31±2 mM, CF and wildtype mice, respectively; p value<0.01; t test). Conclusions/Significance Considering that bicarbonate is the most important pH buffering system in saliva, and the adherence and survival of aciduric bacteria such as S. mutans are enhanced at low pH values, we speculate that the decrease in the bicarbonate content and pH buffering of the saliva is at least partially responsible for the increased severity of lesions observed in the CF mouse. PMID:21304986

Enhancement of ionization efficiency of mass spectrometric analysis from non-electrospray ionization friendly solvents with conventional and novel ionization techniques.

PubMed

Jiang, Ping; Lucy, Charles A

2015-10-15

Electrospray ionization mass spectrometry (ESI-MS) has significantly impacted the analysis of complex biological and petroleum samples. However ESI-MS has limited ionization efficiency for samples in low dielectric and low polarity solvents. Addition of a make-up solvent through a T union or electrospray solvent through continuous flow extractive desorption electrospray ionization (CF-EDESI) enable ionization of analytes in non-ESI friendly solvents. A conventional make-up solvent addition setup was used and a CF-EDESI source was built for ionization of nitrogen-containing standards in hexane or hexane/isopropanol. Factors affecting the performance of both sources have been investigated and optimized. Both the make-up solvent addition and CF-EDESI improve the ionization efficiency for heteroatom compounds in non-ESI friendly solvents. Make-up solvent addition provides higher ionization efficiency than CF-EDESI. Neither the make-up solvent addition nor the CF-EDESI eliminates ionization suppression of nitrogen-containing compounds caused by compounds of the same chemical class. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of fiber-matrix adhesion on the creep behavior of CF/PPS composites: temperature and physical aging characterization

NASA Astrophysics Data System (ADS)

Motta Dias, M. H.; Jansen, K. M. B.; Luinge, J. W.; Bersee, H. E. N.; Benedictus, R.

2016-06-01

The influence of fiber-matrix adhesion on the linear viscoelastic creep behavior of `as received' and `surface modified' carbon fibers (AR-CF and SM-CF, respectively) reinforced polyphenylene sulfide (PPS) composite materials was investigated. Short-term tensile creep tests were performed on ±45° specimens under six different isothermal conditions, 40, 50, 60, 65, 70 and 75 °C. Physical aging effects were evaluated on both systems using the short-term test method established by Struik. The results showed that the shapes of the curves were affected neither by physical aging nor by the test temperature, allowing then superposition to be made. A unified model was proposed with a single physical aging and temperature-dependent shift factor, a_{T,te}. It was suggested that the surface treatment carried out in SM-CF/PPS had two major effects on the creep response of CF/PPS composites at a reference temperature of 40 °C: a lowering of the initial compliance of about 25 % and a slowing down of the creep response of about 1.1 decade.

Measurements of intracellular calcium signals in polarized primary cultures of normal and cystic fibrosis human airway epithelia.

PubMed

Ribeiro, Carla M P

2011-01-01

The airways are continuously challenged by a variety of stimuli including bacteria, viruses, allergens, and inflammatory factors that act as agonists for G protein-coupled receptors (GPCR). Intracellular calcium (Ca(2+) (i)) mobilization in airway epithelia in response to extracellular stimuli regulates key airway innate defense functions, e.g., Ca(2+)-activated Cl(-) secretion, ciliary beating, mucin secretion, and inflammatory responses. Because Ca(2+) (i) mobilization in response to luminal stimuli is larger in CF vs. normal human airway epithelia, alterations in Ca(2+) (i) signals have been associated with the pathogenesis of CF airway disease. Hence, assessment of Ca(2+) (i) signaling has become an important area of CF research. This chapter will focus on measurements of cytoplasmic and mitochondrial Ca(2+) signals resulting from GPCR activation in polarized primary cultures of normal and CF human bronchial epithelia (HBE).

Ecological Risk Assessment of Metals Contamination in the Sediments of Natural Urban Wetlands in Dry Tropical Climate.

PubMed

Rana, Vivek; Maiti, Subodh Kumar; Jagadevan, Sheeja

2016-09-01

The pollution load due to metal contamination in the sediments of urban wetlands (Dhanbad, India) due to illegal release of domestic and industrial wastewater was studied by using various geochemical indices, such as contamination factor (Cf), degree of contamination (Cd), modified degree of contamination (mCd), pollution load index (PLI) and geoaccumulation index (Igeo) for Cu, Co, Cd, Cr and Mn. Cluster analysis (CA) and Principal component analysis (PCA) of metals present in wetland sediments were carried out to assess their origin and relationship with each other. The Cf values for different metals in the wetlands under investigation indicated low to very high level of pollution (Cf ranged between 0.02 and 14.15) with highest Cf (14.15) for Cd. The wetland receiving both domestic and industrial wastewater had the highest values of Cd, mCd and PLI as 17.48, 3.49 and 1.03 respectively.

Infection in cystic fibrosis: impact of the environment and climate.

PubMed

Ramsay, K A; Stockwell, R E; Bell, S C; Kidd, T J

2016-01-01

In many countries numbers of adults with cystic fibrosis (CF) exceed that of children, with median survival predicted to surpass 50 years. Increasing longevity is, in part, due to intensive therapies including eradication of early infection and suppressive therapies and pulmonary exacerbations. Initial infections with common CF pathogens are thought to arise from the natural environment. We review the impact of climate and environment on infection in CF. Specifically, several studies indicate that higher ambient temperatures, proximity to the equator and the summer season may be linked to the increased prevalence of Pseudomonas aeruginosa in people with CF. The environment may also play an important role in the acquisition of Gram negative organisms other than P. aeruginosa. There is emerging data suggesting that climatic and environmental factors are likely to impact on the risk of infection with NTM and fungi in people which are found extensively throughout the natural environment.

Methodological Variables in the Analysis of Cell-Free DNA.

PubMed

Bronkhorst, Abel Jacobus; Aucamp, Janine; Pretorius, Piet J

2016-01-01

In recent years, cell-free DNA (cfDNA) analysis has received increasing amounts of attention as a potential non-invasive screening tool for the early detection of genetic aberrations and a wide variety of diseases, especially cancer. However, except for some prenatal tests and BEAMing, a technique used to detect mutations in various genes of cancer patients, cfDNA analysis is not yet routinely applied in clinical practice. Although some confusing biological factors inherent to the in vivo setting play a key part, it is becoming increasingly clear that this struggle is mainly due to the lack of an analytical consensus, especially as regards quantitative analyses of cfDNA. In order to use quantitative analysis of cfDNA with confidence, process optimization and standardization are crucial. In this work we aim to elucidate the most confounding variables of each preanalytical step that must be considered for process optimization and equivalence of procedures.

The essential oil qualitative and quantitative composition in the needles of Pinus sylvestris L. growing along industrial transects.

PubMed

Kupcinskiene, Eugenija; Stikliene, Aida; Judzentiene, Asta

2008-10-01

The aim of this study was to evaluate composition of the essential oils in the needles of Pinus sylvestris growing in the areas affected by a cement factory (CF), and an oil refinery (OR). Volatile components of the needles were analyzed by GC and GC/MS. The most heavily polluted CF stand had significantly higher concentration of gamma-Terpinene, Caryophyllene oxide in the current-year needles, while higher concentration of delta-3-Carene, alpha-Terpinene, gamma-Terpinene and Terpinolene was documented for 1-year-old needles. The most heavily polluted OR stand had a significantly higher concentration of Sabinene+beta-Pinene, 1-epi-Cubenol in the current-year needles and a significantly higher concentration of Camphene, Sabinene+beta-Pinene, Myrcene, alpha-Cadinene, 1-epi-Cubenol in the 1-year-old needles than the least polluted site. Along transects an increase in the amount of some diterpenes and a decrease in the components of the shorter chain essential oils was observed. These effects could be at least partially attributed to SO(2).

Lung Infections Associated with Cystic Fibrosis

PubMed Central

Lyczak, Jeffrey B.; Cannon, Carolyn L.; Pier, Gerald B.

2002-01-01

While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host. PMID:11932230

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Fungal infections and treatment in cystic fibrosis.

PubMed

Middleton, Peter G; Chen, Sharon C-A; Meyer, Wieland

2013-11-01

This review summarizes some of the important recent findings concerning fungal airway infections in patients with cystic fibrosis (CF). For many years, both researchers and clinicians have focused on the problems in CF caused by chronic bacterial airway infection with organisms such as Haemophilus, Staphylococcus and Pseudomonas. However, until recently, the lack of sensitive culture techniques to isolate fungi in sputum, bronchoalveolar lavage fluid and other respiratory tract samples has limited the recognition of fungal species and their possible role in CF airway infections. Recent studies using fungal-selective culture media and molecular techniques have shown a plethora of different fungal species in the sputum expectorated from CF patients. Cross-sectional studies have shown associations between Aspergillus and Candida in the sputum and worse lung function. The presence of allergic bronchopulmonary aspergillosis is likely to be a negative prognostic factor, but whether simple fungal colonization itself indicates future problems is not clear. Current research is now examining these epidemiological associations to try to determine the clinical implications. This will help determine whether fungal colonization/infection is associated with worse outcome in CF patients. At present, there is no conclusive evidence that fungal organisms cause respiratory decline. Recent studies of antifungal therapy in CF patients have reported differing results, so further investigations in this area are needed.

An assessment of potential impact of alternative fluorocarbons on tropospheric ozone

NASA Technical Reports Server (NTRS)

Niki, Hiromi

1990-01-01

While the chlorofuorocarbons (CFCs) such as CFC-11 (CFCl3) and CFC-12 (CF2Cl2) are chemically inert in the troposphere, the hydrogen-containing halocarbons being considered as their replacements can, to a large extent, be removed in the troposphere by the HO radical. These alternative halocarbons include the hydrochlorofluorocarbons (HCFCs) 123 (CF3CHCl2), 141b (CFCl2CH3), 142b (CF2ClCH3), 22 (CHF2Cl), and 124 (CF3CHFCl) and the hydrofluorocarbons (HCFs) 134a (CF3CH2F), 152a (CHF2CH3) and 125 (CF3CHF2). Listed are the rate constants (k) for the HO radical reaction of these compounds and their estimated chemical lifetimes in the troposphere. In this table, values of the lifetimes of these selected HCFCs and HCFs are seen to vary by more than a factor of more than ten ranging from 1.6 years for HFC 152a and HCFC 125 to as long as 28 years for HFC 125. Clearly, from the standpoint of avoiding or minimizing impact on stratospheric O3, those halocarbons with short tropospheric lifetimes are the desirable alternates. However, potential environmental consequences of their degradation in the troposphere should be assessed and taken into account in the selection process.

What follows newborn screening? An evaluation of a residential education program for parents of infants with newly diagnosed cystic fibrosis.

PubMed

Sawyer, Susan M; Glazner, Judith A

2004-08-01

The diagnosis of a severe life-limiting condition, such as cystic fibrosis (CF), is generally followed by assessment and treatment of the child and education and counseling for parents. The introduction of newborn screening for CF provides an opportunity for standardized assessment and education. The aim of this study was to evaluate a 5-day residential assessment and education program for parents of infants who receive a diagnosis of CF after newborn screening. Eligible parents had a 6- to 30-month-old infant with CF diagnosed by newborn screening. Parents were interviewed by telephone using a structured questionnaire that addressed 3 main themes: 1) initial communication of the diagnosis of CF, 2) the perceived value of the 5-day assessment and education program, and 3) the perceived advantages and disadvantages of the residential component (Care-By-Parent unit) of the program. Fifteen of 17 eligible families took part in the 5-day assessment and education program, 12 of whom used the residential Care-By-Parent unit. At the end of the program, parents believed that they had the knowledge and skills required to manage their child's CF at home. One hundred percent endorsed the timing of the assessment and education program immediately after the child's diagnosis and would recommend it to other families in the same situation. Perceived advantages of the residential program were not having to travel (89%), being able to concentrate on CF (50%), and the benefit of a "home base" at the hospital (39%). Twenty-two percent reported that financial costs related to participation (paternal time off work) were a disadvantage, 17% reported additional strain on family members caring for siblings, and 17% mentioned lack of comfort within the unit. This time-intensive residential program was evaluated positively by parents of children with newly diagnosed CF. It provides a model for education programs after the diagnosis of CF by newborn screening, as well as for other pediatric conditions that require intensive parent education.

Improved urban stormwater treatment and pollutant removal pathways in amended wet detention ponds.

PubMed

Istenič, Darja; Arias, Carlos A; Vollertsen, Jes; Nielsen, Asbjørn H; Wium-Andersen, Tove; Hvitved-Jacobsen, Thorkild; Brix, Hans

2012-01-01

Dissolved and colloidal bound pollutants are generally poorly removed from stormwater in wet detention ponds. These fractions are, however, the most bio-available, and therefore three wet detention ponds were amended with planted sand filters, sorption filters and addition of precipitation chemicals to enhance the removal of dissolved pollutants and pollutants associated with fine particles and colloids. The three systems treated runoff from industrial, residential and combined (residential and highway) catchments and had permanent volumes of 1,990, 6,900 and 2,680 m(3), respectively. The treatment performance of the ponds for elimination of total suspended solids (TSS), total nitrogen (Tot-N), total phosphorous (Tot-P), PO(4)-P, Pb, Zn, Cd, Ni, Cr, Cu, Hg were within the range typically reported for wet detention ponds, but the concentrations of most of the pollutants were efficiently reduced by the planted sand filters at the outlets. The sorption filters contributed to further decrease the concentration of PO(4)-P from 0.04 ± 0.05 to 0.01 ± 0.01 mg L(-1) and were also efficient in removing heavy metals. Dosing of iron sulphate to enrich the bottom sediment with iron and dosing of aluminium salts to the inlet water resulted in less growth of phytoplankton, but treatment performance was not significantly affected. Heavy metals (Pb, Zn, Cd, Ni, Cr and Cu) accumulated in the sediment of the ponds. The concentrations of Zn, Ni, Cu and Pb in the roots of the wetland plants were generally correlated to the concentrations in the sediments. Among 13 plant species investigated, Rumex hydrolapathum accumulated the highest concentrations of heavy metals in the roots (Concentration Factor (CF) of 4.5 and 5.9 for Zn and Ni, respectively) and Iris pseudacorus the lowest (CF < 1). The translocation of heavy metals from roots to the aboveground tissues of plants was low. Therefore the potential transfer of heavy metals from the metal-enriched sediment to the surrounding ecosystem via plant uptake and translocation is negligible.

Quantitative analysis of titanium concentration using calibration-free laser-induced breakdown spectroscopy (LIBS)

NASA Astrophysics Data System (ADS)

Zaitun; Prasetyo, S.; Suliyanti, M. M.; Isnaeni; Herbani, Y.

2018-03-01

Laser-induced breakdown spectroscopy (LIBS) can be used for quantitative and qualitative analysis. Calibration-free LIBS (CF-LIBS) is a method to quantitatively analyze concentration of elements in a sample in local thermodynamic equilibrium conditions without using available matrix-matched calibration. In this study, we apply CF-LIBS for quantitative analysis of Ti in TiO2 sample. TiO2 powder sample was mixed with polyvinyl alcohol and formed into pellets. An Nd:YAG pulsed laser at a wavelength of 1064 nm was focused onto the sample to generate plasma. The spectrum of plasma was recorded using spectrophotometer then compared to NIST spectral line to determine energy levels and other parameters. The value of plasma temperature obtained using Boltzmann plot is 8127.29 K and electron density from calculation is 2.49×1016 cm-3. Finally, the concentration of Ti in TiO2 sample from this study is 97% that is in proximity with the sample certificate.

Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial.

PubMed

Mansour, Anthony G; Hariri, Essa; Daaboul, Yazan; Korjian, Serge; El Alam, Andrew; Protogerou, Athanase D; Kilany, Hala; Karam, Albert; Stephan, Antoine; Bahous, Sola Aoun

2017-09-01

Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 μg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P < .001). Mean dp-ucMGP concentrations were also significantly reduced by 55.1% following menaquinone-7 supplementation with a reduction in the prevalence of subclinical deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis and transplantation, and the change in 24-hour mean arterial pressure, the improvement in arterial stiffness was independently associated with the reduction in dp-ucMGP concentration (P = .014).Among renal transplant recipients with stable graft function, vitamin K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580). Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

PubMed Central

Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

2018-01-01

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) (P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis. PMID:29399276

Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

PubMed

MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

2017-05-01

The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Factors influencing the production of cellulase by Aspergillus fumigatus (Fresenius).

PubMed

Stewart, J C; Parry, J B

1981-07-01

During growth in liquid culture containing a single cellulosic or non-cellulosic carbon source, a newly isolated strain of Aspergillus fumigatus released cellulases into the medium; the amounts produced depended on the nitrogen source, the type and concentration of the carbon source, pH and temperature. Extracellular cellulolytic activity was still increasing after incubation for 60 d with 1% (W/V) CF11 cellulose, (NH4)2SO4 as nitrogen source and a starting pH of 7. The activities of the new isolate were compared with those of A. fumigatus IMI 143864 and Trichoderma reesei QM6a (ATCC 13631) and it was shown to be a good producer of beta-glucosidase.

[Insights into cystic fibrosis-related bone disease].

PubMed

Braun, C; Bacchetta, J; Reix, P

2016-08-01

With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Modifier genes in Mendelian disorders: the example of cystic fibrosis

PubMed Central

Cutting, Garry R.

2011-01-01

In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention. PMID:21175684

Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin.

PubMed

Liu, Feng-Cheng; Lu, Jeng-Wei; Chien, Chiao-Yun; Huang, Hsu-Shan; Lee, Chia-Chung; Lien, Shiu-Bii; Lin, Leou-Chyr; Chen, Liv Weichien; Ho, Yi-Jung; Shen, Min-Chung; Ho, Ling-Jun; Lai, Jenn-Haung

2018-05-14

In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory flavonoid present in many different fruits and vegetables. We investigated the immunomodulatory effects of this compound, namely 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2 H -benzo[ e ][1,3]oxazine-2,4(3 H )-dione (Cf-02), in a side-by-side comparison with quercetin. Chondrocytes were isolated from pig joints or the joints of patients with osteoarthritis that had undergone total knee replacement surgery. Several measures were used to assess the immunomodulatory potency of these compounds in tumor necrosis factor (TNF-α)-stimulated chondrocytes. Characterization included the protein and mRNA levels of molecules associated with arthritis pathogenesis as well as the inducible nitric oxide synthase (iNOS)⁻nitric oxide (NO) system and matrix metalloproteinases (MMPs) in cultured chondrocytes and proteoglycan, and aggrecan degradation in cartilage explants. We also examined the activation of several important transcription factors, including nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription-3 (STAT-3), and activator protein-1 (AP-1). Our overall results indicate that the immunomodulatory potency of Cf-02 is fifty-fold more efficient than that of quercetin without any indication of cytotoxicity. When tested in vivo using the induced edema method, Cf-02 was shown to suppress inflammation and cartilage damage. The proposed method shows considerable promise for the identification of candidate disease-modifying immunomodulatory drugs and leads compounds for arthritis therapeutics.

Dissociative electron attachment and vibrational excitation of CF{sub 3}Cl: Effect of two vibrational modes revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tarana, Michal; JILA, University of Colorado and NIST, Boulder, Colorado 80309-0440; Houfek, Karel

We present a study of dissociative electron attachment and vibrational excitation processes in electron collisions with the CF{sub 3}Cl molecule. The calculations are based on the two-dimensional nuclear dynamics including the C-Cl symmetric stretch coordinate and the CF{sub 3} symmetric deformation (umbrella) coordinate. The complex potential energy surfaces are calculated using the ab initio R-matrix method. The results for dissociative attachment and vibrational excitation of the umbrella mode agree quite well with experiment whereas the cross section for excitation of the C-Cl symmetric stretch vibrations is about a factor-of-three too low in comparison with experimental data.

Cross-Fostering Implications for Pig Mortality, Welfare and Performance.

PubMed

Calderón Díaz, Julia A; García Manzanilla, Edgar; Diana, Alessia; Boyle, Laura A

2018-01-01

This study aimed to (1) identify cross-fostering (CF) practices employed on a commercial farm; (2) characterize CF pigs according to litter of origin traits, and (3) investigate the implications of CF practices on pig mortality, performance and welfare. This was an observational study whereby pigs were managed according to normal farming practice. Pigs ( n = 1,016) born within 1 week were classified as non-CF (NCF); CF during the first (CFW1) and second or third (CFW2+) weeks of lactation. Pigs were individually weighed and inspected for the presence of tail (TL), ear (EL) and body lesions (BL) at weaning (7.03 ± 1.61 kg) and at the end of the first (12.9 ± 3.03 kg) and second (31.9 ± 5.50 kg) weaner and grower (66.3 ± 9.12 kg) stages. Mortality was recorded through to slaughter (c. 115 kg). At slaughter, TL were scored and carcass characteristics, presence of pleurisy, enzootic pneumonia, pericarditis and heart condemnations were recorded. 40.8% of CF pigs were CFW1; ANOVA tests revealed these were born to sows with a higher number of piglets born alive than NCF pigs (14.6 ± 2.61 and 12.8 ± 2.68, respectively). The remaining 59.2% of CF pigs were CFW2+; these were, on average, 0.14 kg lighter at birth than NCF pigs. Therefore, a nested case control design was retrospectively applied whereby pigs with complete records to slaughter, were matched for these variables to investigate associations between CF weeks, welfare and performance traits. Growth performance did not differ between CF week ( P > 0.05); however, CFW2+ carcasses were 4.9 kg lighter ( P < 0.05) compared with NCF and CFW1 pigs. EL were more likely in CFW1 compared to NCF and CFW2+ ( P < 0.05) pigs. To investigate the effect of CF week on the risk of mortality, all 1,016 pigs were used. CF pigs were at higher risk of death ( P < 0.05) with similar odds in CFW1 and CFW2+ pigs compared with NCF pigs, although other underlying factors could contribute to this result. Performance and health traits were similar between CF weeks. Early cross-fostering appeared to influence the presence of ear lesions but the mechanism is likely indirect and difficult to explain.

Transformation of carbon tetrachloride and chloroform by trichloroethene respiring anaerobic mixed cultures and supernatant.

PubMed

Vickstrom, Kyle E; Azizian, Mohammad F; Semprini, Lewis

2017-09-01

Carbon tetrachloride (CT) and chloroform (CF) were transformed in batch reactor experiments conducted with anaerobic dechlorinating cultures and supernatant (ADC + S) harvested from continuous flow reactors. The Evanite (EV) and Victoria/Stanford (VS) cultures, capable of respiring trichloroethene (TCE), 1,2-cis-dichloroethene (cDCE), and vinyl chloride (VC) to ethene (ETH), were grown in continuous flow reactors receiving an influent feed of saturated TCE (10 mM; 60 mEq) and formate (45 mM; 90 mEq) but no CT or CF. Cells and supernatant were harvested from the chemostats and inoculated into batch reactors at the onset of each experiment. CT transformation was complete following first order kinetics with CF, DCM and CS 2 as the measurable transformation products, representing 20-40% of the original mass of CT, with CO 2 likely the unknown transformation product. CF was transformed to DCM and likely CO 2 at an order of magnitude rate lower than CT, while DCM was not further transformed. An analytical first order model including multiple key reactions effectively simulated CT transformation, product formation and transformation, and provided reasonable estimates of transformation rate coefficients. Biotic and abiotic treatments indicated that CT was mainly transformed via abiotic processes. However, the presence of live cells was associated with the transformation of CF to DCM. In biotic tests both TCE and CT were simultaneously transformed, with TCE transformed to ETH and approximately 15-53% less CF formed via CT transformation. A 14-day exposure to CF (CF max  = 1.4 μM) reduced all rates of chlorinated ethene respiration by a factor of 10 or greater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cystic Fibrosis Revisited - a Review Study.

PubMed

Klimova, Blanka; Kuca, Kamil; Novotny, Michal; Maresova, Petra

2017-01-01

Cystic fibrosis (CF) is an incurable, chronic disease, which causes severe damages to respiratory and digestive tracts. It is the most common genetically inherited disease among caucasians. This disease is caused by defects in CF genes, the so-called mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene population. At present over 100,000 people suffer from this disease worldwide. The purpose of this review study is to describe the pathophysiology of CF and provide the latest information on its diagnosis and treatment therapies with respect to the improvement of patient's quality of life and emphasis on targeted specialized care. The methodological approaches include a method of literature review of available sources exploring the issue of cystic fibrosis both from a global and specific perspective point of view. A search was performed in the databases PubMed, MEDLINE, Web of Science, Scopus, Springer and ScienceDirect. Furthermore, other sources cited in the analyzed studies were also examined. On the basis of evaluation of these literature sources, the research issue was explored. The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted. CF requires an integrated treatment approach in specialized CF centers, involving various factors contributing to a better patient's state of health in the form of relevant and well-balanced non-pharmacological and pharmacological therapies. In addition, further large scale clinical trials are needed in order to develop compounds that are aimed at the most common classes of CFTR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Environmental allergies and respiratory morbidities in cystic fibrosis.

PubMed

Collaco, Joseph M; Morrow, Christopher B; Green, Deanna M; Cutting, Garry R; Mogayzel, Peter J

2013-09-01

Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Although environmental factors account for 50% of the variation in CF lung function, few specific exposures have been identified. Studies using small study samples focusing on environmental allergies in CF have had inconsistent results. Our objective was to examine the role of environmental allergies in upper and lower respiratory tract morbidities in CF. A total of 1,321 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of environmental allergies. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Within the study sample 14% reported environmental allergies. Environmental allergies were associated with a higher risk of sinus disease (adjusted OR: 2.68; P < 0.001) and nasal polyps (adjusted OR: 1.74; P = 0.003). Environmental allergies were also associated with a more rapid decline in lung function (additional -1.1%/year; P = 0.001). However, allergies were associated with a later median age of acquisition of Pseudomonas aeruginosa (6.6 years vs. 4.4 years; log rank P = 0.027). The reported use of common allergy medications, anti-histamines and leukotriene inhibitors, did not alter the frequency of respiratory morbidities. Environmental allergies are associated with an increased risk of sinus disease and nasal polyps and a more rapid decline in CF lung function, but may have a protective effect against the acquisition of P. aeruginosa. Prospective studies are needed to confirm these associations which have implications for more aggressive management of allergies. Copyright © 2012 Wiley Periodicals, Inc.

Environmental Allergies and Respiratory Morbidities in Cystic Fibrosis

PubMed Central

Collaco, Joseph M.; Morrow, Christopher B.; Green, Deanna M.; Cutting, Garry R.; Mogayzel, Peter J.

2012-01-01

SUMMARY Background Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Although environmental factors account for 50% of the variation in CF lung function, few specific exposures have been identified. Studies using small study samples focusing on environmental allergies in CF have had inconsistent results. Our objective was to examine the role of environmental allergies in upper and lower respiratory tract morbidities in CF. Methods A total of 1321 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of environmental allergies. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Results Within the study sample 14% reported environmental allergies. Environmental allergies were associated with a higher risk of sinus disease (adjusted OR: 2.68; p<0.001) and nasal polyps (adjusted OR: 1.74; p=0.003). Environmental allergies were also associated with a more rapid decline in lung function (additional −1.1%/year; p=0.001). However, allergies were associated with a later median age of acquisition of Pseudomonas aeruginosa (6.6 yo vs. 4.4 yo; log rank p=0.027). The reported use of common allergy medications, anti-histamines and leukotriene inhibitors, did not alter the frequency of respiratory morbidities. Conclusions Environmental allergies are associated with an increased risk of sinus disease and nasal polyps and a more rapid decline in CF lung function, but may have a protective effect against the acquisition of P. aeruginosa. Prospective studies are needed to confirm these associations which have implications for more aggressive management of allergies. PMID:23143815

Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study.

PubMed

Efrati, Ori; Nir, Judith; Fraser, Drora; Cohen-Cymberknoh, Malena; Shoseyov, David; Vilozni, Daphna; Modan-Moses, Dalit; Levy, Ran; Szeinberg, Amir; Kerem, Eitan; Rivlin, Joseph

2010-02-01

Patients with cystic fibrosis (CF) presenting with meconium ileus (MI) tend to have worse outcomes than those without MI. We evaluated the clinical characteristics and survival rates among Israeli patients with CF with and without MI after a prolonged follow-up (15-30 years). A multicenter retrospective study. Forty-nine patients with CF, representing 13.8% of all patients with CF in Israel, presented with MI (current age 17.4 +/- 7.9 years) between 1975 and 2006. They were compared with 38 patients with CF (current age 19.3 +/- 6.5 years) without MI matched by sex and CF transmembrane conductance regulator mutation. A total of 66.2% of patients with MI and 73.6% without MI were followed for a prolonged period (24.9 +/- 2.7 years). Of the patients with MI, 31 were managed operatively, whereas 18 were treated successfully with gastrograffin enema, with similar clinical outcomes. Five patients in the MI group and 3 in the control group died during the study period. Bacterial colonization, z score of body mass index, and pulmonary function tests were similar in patients with and without MI in the long term. In younger patients, many clinical parameters were more prevalent in patients with MI (P = 0.004). However, these differences disappeared after the long-term follow-up (up to 31-years). Patients with CF presenting with MI had similar pulmonary function and nutritional status, as well as survival rates as did the control patients without MI. The distinct genetic mutation found in our population may explain in part the favorable results compared with other studies. In addition, it seems that early diagnosis and treatment of MI in patients with CF may be beneficial, subsequently lowering morbidity, and increasing survival.

Pretransplant Aspergillus colonization of cystic fibrosis patients and the incidence of post-lung transplant invasive aspergillosis.

PubMed

Luong, Me-Linh; Chaparro, Cecilia; Stephenson, Anne; Rotstein, Coleman; Singer, Lianne G; Waters, Valerie; Azad, Sassan; Keshavjee, Shaf; Tullis, Elizabeth; Husain, Shahid

2014-02-15

Invasive aspergillosis (IA) is an important cause of morbidity and mortality among patients undergoing lung transplant. Cystic fibrosis-lung transplant recipients (CF-LTRs) may be at greater risk of IA following lung transplantation because of the presence of Aspergillus in their airways before transplantation. This study evaluated the impact of pretransplant Aspergillus colonization on the risk for IA among CF-LTRs. A single-center retrospective cohort study of CF-LTRs was conducted between 2006 and 2010. Respiratory tract cultures before transplantation were reviewed to identify patients with pretransplant Aspergillus colonization. Patients with positive Aspergillus sputum culture or positive bronchoalvelolar lavage (BAL) galactomannan after transplantation were classified as having colonization or disease according to the International Society of Heart and Lung Transplantation criteria. A total of 93 CF patients underwent lung transplantation. Seventy percent (65/93) of CF-LTRs had pretransplant Aspergillus colonization. Thirty-six patients had positive intraoperative Aspergillus culture from the native lung BAL. Overall, 22.5% (20/93) of CF-LTRs developed IA. Median time to IA was 42 days following transplantation. Positive intraoperative Aspergillus culture (OR 4.36, 95% CI 1.35-14.05, P=0.01) and treatment for acute cellular rejection within 90 days after transplantation (OR 3.53, 95% CI 1.03-12.15, P=0.05) were independent risk factors for IA. Antifungal prophylaxis was administered to 61% (57/93) of CF-LTRs. One-year mortality rate was 16% (15/93). IA was not associated with increased risk of death (OR 2.10, 95% CI 0.62-7.06, P=0.23). Pretransplant Aspergillus colonization is frequent among CF-LTRs and a positive intraoperative Aspergillus culture produced a fourfold higher risk of developing IA.

In Vitro Analysis of Pseudomonas aeruginosa Virulence Using Conditions That Mimic the Environment at Specific Infection Sites.

PubMed

Colmer-Hamood, J A; Dzvova, N; Kruczek, C; Hamood, A N

2016-01-01

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes chronic lung infection in patients with cystic fibrosis (CF) and acute systemic infections in severely burned patients and immunocompromised patients including cancer patients undergoing chemotherapy and HIV infected individuals. In response to the environmental conditions at specific infection sites, P. aeruginosa expresses certain sets of cell-associated and extracellular virulence factors that produce tissue damage. Analyzing the mechanisms that govern the production of these virulence factors in vitro requires media that closely mimic the environmental conditions within the infection sites. In this chapter, we review studies based on media that closely resemble three in vivo conditions, the thick mucus accumulated within the lung alveoli of CF patients, the serum-rich wound bed and the bloodstream. Media resembling the CF alveolar mucus include standard laboratory media supplemented with sputum obtained from CF patients as well as prepared synthetic mucus media formulated to contain the individual components of CF sputum. Media supplemented with serum or individual serum components have served as surrogates for the soluble host components of wound infections, while whole blood has been used to investigate the adaptation of pathogens to the bloodstream. Studies using these media have provided valuable information regarding P. aeruginosa gene expression in different host environments as varying sets of genes were differentially regulated during growth in each medium. The unique effects observed indicate the essential role of these in vitro media that closely mimic the in vivo conditions in providing accurate information regarding the pathogenesis of P. aeruginosa infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.

PubMed

Esposito, Speranza; Tosco, Antonella; Villella, Valeria R; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

2016-12-01

Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.

Employment and work disability in adults with cystic fibrosis.

PubMed

Laborde-Castérot, Hervé; Donnay, Carole; Chapron, Jeanne; Burgel, Pierre-Régis; Kanaan, Reem; Honoré, Isabelle; Dusser, Daniel; Choudat, Dominique; Hubert, Dominique

2012-03-01

As a result of prolonged survival, more patients with cystic fibrosis (CF) participate in the labour force. The aim of this study was to evaluate their education, occupation levels and risk factors for work disability. 207 patients answered a self-administered questionnaire about their educational level and work status. Independently, medical records were reviewed for illness severity indicators. 39 patients (19%) were students, 117 (57%) were in the labour force, 13 (6%) were seeking employment and 38 (18%) were inactive. CF patients had a higher educational level and were more likely to hold skilled jobs and to work part time than the general population. FEV1 and educational level were the strongest predictive factors of disability. Many CF patients have access to professional life. Their higher educational levels improve the chances of attaining employment, which highlights the need for career counselling. Working part time helps to maintain employment despite declining health. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.

PubMed

Saussereau, Emilie Lyne; Roussel, Delphine; Diallo, Siradiou; Debarbieux, Laurent; Edelman, Aleksander; Sermet-Gaudelus, Isabelle

2013-01-01

Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR) defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF). Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE)) to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE) in CF mice must be well characterized for correct interpretation. We performed V(TE) measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT) littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice. We determined the typical V(TE) values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(-) solution was considered to indicate a normal response. These data will make it possible to interpret changes in nasal V(TE) in mouse models of CF, in future preclinical studies.

A paradox resolved: Sulfide acquisition by roots of seep tubeworms sustains net chemoautotrophy

PubMed Central

Freytag, John K.; Girguis, Peter R.; Bergquist, Derk C.; Andras, Jason P.; Childress, James J.; Fisher, Charles R.

2001-01-01

Vestimentiferan tubeworms, symbiotic with sulfur-oxidizing chemoautotrophic bacteria, dominate many cold-seep sites in the Gulf of Mexico. The most abundant vestimentiferan species at these sites, Lamellibrachia cf. luymesi, grows quite slowly to lengths exceeding 2 meters and lives in excess of 170–250 years. L. cf. luymesi can grow a posterior extension of its tube and tissue, termed a “root,” down into sulfidic sediments below its point of original attachment. This extension can be longer than the anterior portion of the animal. Here we show, using methods optimized for detection of hydrogen sulfide down to 0.1 μM in seawater, that hydrogen sulfide was never detected around the plumes of large cold-seep vestimentiferans and rarely detectable only around the bases of mature aggregations. Respiration experiments, which exposed the root portions of L. cf. luymesi to sulfide concentrations between 51–561 μM, demonstrate that L. cf. luymesi use their roots as a respiratory surface to acquire sulfide at an average rate of 4.1 μmol⋅g−1⋅h−1. Net dissolved inorganic carbon uptake across the plume of the tubeworms was shown to occur in response to exposure of the posterior (root) portion of the worms to sulfide, demonstrating that sulfide acquisition by roots of the seep vestimentiferan L. cf. luymesi can be sufficient to fuel net autotrophic total dissolved inorganic carbon uptake. PMID:11687647

The L441P mutation of cystic fibrosis transmembrane conductance regulator and its molecular pathogenic mechanisms in a Korean patient with cystic fibrosis.

PubMed

Gee, Heon Yung; Kim, Chang Keun; Kim, So Won; Lee, Ji Hyun; Kim, Jeong-Ho; Kim, Kyung Hwan; Lee, Min Goo

2010-01-01

Cystic fibrosis (CF) is an autosomal recessive disorder usually found in populations of white Caucasian descent. CF is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. A 5-yr-old Korean girl was admitted complaining of coughing and greenish sputum. Chest radiographs and computed tomographic (CT) scan revealed diffuse bronchiectasis in both lungs. The patient had chronic diarrhea and poor weight gain, and the abdominal pancreaticobiliary CT scan revealed atrophy of the pancreas. Finally, CF was confirmed by the repeated analysis of the quantitative pilocarpine iontophoresis test. The chloride concentration of sweat samples taken from both forearms of the pateint was an average of 88.7 mM/L (normal value <40 mM/L). After a comprehensive search for mutations in the CFTR gene, the patient was found to carry the non-synonymous L441P mutation in one allele. Molecular physiologic analysis of the L441P mutation of CFTR revealed that the L441P mutation completely abolished the CFTR Cl(-) channel activity by disrupting proper protein folding and membrane trafficking of CFTR protein. These results confirmed the pathogenicity of the L441P mutation of CFTR circulating in the Korean population. The possibility of CF should be suspected in patients with chronic bronchiectasis, although the frequency of CF is relatively rare in East Asia.

Atmospheric lifetime of SF5CF3

NASA Astrophysics Data System (ADS)

Takahashi, K.; Nakayama, T.; Matsumi, Y.; Solomon, S.; Gejo, T.; Shigemasa, E.; Wallington, T. J.

2002-08-01

The vacuum ultraviolet (VUV) absorption spectrum of SF5CF3 was measured over the range 106-200 nm. At 121.6 nm, σ(base e) = (7.8 +/- 0.6) × 10-18 cm2 molecule-1, in which quoted uncertainty includes two standard deviation from the least-square fit in the Beer-Lambert plot and our estimate of potential systematic errors associated with measurements of the reactant concentrations. The VUV spectrum and literature data for electron attachment and ion-molecule reactions were incorporated into a model of the stratosphere, mesosphere, and lower thermosphere. This information provides better constraints on the atmospheric lifetime and hence on the potential of this highly radiatively-active trace gas to influence the climate system. The atmospheric lifetime of SF5CF3 is dominated by dissociative electron attachment and is estimated to be approximately 950 years. Solar proton events could reduce this to a lower limit of 650 years.

Cystic fibrosis transmembrane regulator gene (CFTR) is associated with abnormal enamel formation.

PubMed

Arquitt, C K; Boyd, C; Wright, J T

2002-07-01

Cystic fibrosis (CF), a chloride ion transport disorder, is caused by mutations of the cftr gene and is the most common autosomal-recessive heritable disease in Caucasians. CFTR knockout mice have enamel with crystallite defects, retained protein, and hypomineralization, suggesting a role for CFTR in enamel formation and mineralization. This investigation examined CFTR expression and elemental composition in developing murine incisor teeth. RT-PCR showed cftr mRNA expression in the normal mouse apical incisor tissue but not in the CFTR knockout tissue. Elemental analysis by energy-dispersive x-ray spectroscopy showed relatively decreased chloride in secretory-stage CF enamel. Iron and potassium were significantly increased, and calcium was significantly decreased (p value = 0.05) in the CF mature enamel. Abnormal enamel mineralization, ion concentrations, and molecular evidence of cftr mRNA expression by odontogenic cells strongly suggest that CFTR plays an important role in enamel formation.

A comparison of biomarker responses in juvenile diploid and ...

EPA Pesticide Factsheets

Influence of waterborne butachlor (BUC), a commonly used pesticide, on morphometric, biochemical, and molecular biomarkers was evaluated in juvenile, full sibling, diploid and triploid African catfish (Clarias gariepinus). Fish were exposed for 21 days to one of three concentrations of BUC [mean measured µg/L: 22, 44 or 60]. Unexposed (control) triploids were heavier and longer and had higher visceral-somatic index (VSI) than diploids. Also, they had lighter liver weight (HSI) and showed lower transcript levels of brain gonadotropin-releasing hormone (GnRH), aromatase (cyp191b) and fushi tarazu-factor (ftz-f1), and plasma testosterone levels than diploids. Butachlor treatments had no effects, in either diploid or triploid fish, on VSI, HSI, weight or length changes, condition factor (CF), levels of plasma testosterone, 17-β estradiol (E2), cortisol, cholesterol, or mRNA levels of brain tryptophan hydroxylase (tph2), forkhead box L2 (foxl2), and 11 β-hydroxysteroid dehydrogenase type 2 (11β-hsd2). Expressions of cyp191b and ftz-f1 in triploids were upregulated by the two highest concentrations of BUC. In diploid fish, however, exposures to all BUC concentrations decreased GnRH transcription and the medium BUC concentration decreased ftz-f1 transcription. Substantial differences between ploidies in basal biomarker responses are consistent with the reported impaired reproductive axis in triploid C. gariepinus. Furthermore, the present study showed the low impac

Comprehensive vacuum ultraviolet photoionization study of the CF3• trifluoromethyl radical using synchrotron radiation

NASA Astrophysics Data System (ADS)

Dossmann (Soldi-Lose), Héloïse; Garcia, Gustavo A.; Nahon, Laurent; de Miranda, Barbara K. C.; Alcaraz, Christian

2012-05-01

The trifluoromethyl radical, CF3•, is studied for the first time by means of threshold photoelectron spectroscopy (TPES). The radical is produced in the gas phase using the flash-pyrolysis technique from hexafluoroethane as a precursor. CF3+ total ion yield and mass-selected TPES of the radical are recorded using a spectrometer based upon velocity map imaging and Wiley-McLaren time-of-flight coupled to the synchrotron radiation. The high resolution of the instrument and of the photons allows the observation of rich vibrational progressions in the TPES of CF3•. By using Franck-Condon factors computed by Bowman and coworkers, we have been able to simulate the TPES. The initial vibrational temperature of the radical beam has been evaluated at 350 ± 70 K. The structures have been identified as transitions between (n1,n2) and (n1+,n2+) vibrational levels of CF3 and CF3+ with small excitation of the breathing mode, ν1+, and large excitation (n2+ = 10-26) of the umbrella mode, ν2+, in the cation. From the energy separation between the two resolved peaks of each band, a value of 994 ± 16 cm-1 has been derived for the ν1+ breathing frequency of CF3+. For the high-lying n2+ levels, the apparent ν2+ umbrella spacing, 820 ± 14 cm-1, is fairly constant. Taking into account the ν2+ anharmonicity calculated by Bowman and coworkers, we have deduced ν2+ = 809 ± 14 cm-1, and semi-empirical estimations of the adiabatic ionization energy IEad.(CF3•) are proposed in good agreement with most of previous works. A value of the vertical ionization potential, IEvert.(CF3•) = 11.02 eV, has been derived from the observation of a photoelectron spectrum recorded at a fixed photon energy of 12 eV.

The luminosity function for different morphological types in the CfA Redshift Survey

NASA Technical Reports Server (NTRS)

Marzke, Ronald O.; Geller, Margaret J.; Huchra, John P.; Corwin, Harold G., Jr.

1994-01-01

We derive the luminosity function for different morphological types in the original CfA Redshift Survey (CfA1) and in the first two slices of the CfA Redshift Survey Extension (CfA2). CfA1 is a complete sample containing 2397 galaxies distributed over 2.7 steradians with m(sub z) less than or equal 14.5. The first two complete slices of CfA2 contain 1862 galaxies distributed over 0.42 steradians with m(sub z)=15.5. The shapes of the E-S0 and spiral luminosity functions (LF) are indistinguishable. We do not confirm the steeply decreasing faint end in the E-S0 luminosity function found by Loveday et al. for an independent sample in the southern hemisphere. We demonstrate that incomplete classification in deep redshift surveys can lead to underestimates of the faint end of the elliptical luminosity function and could be partially responsible for the difference between the CfA survey and other local field surveys. The faint end of the LF for the Magellanic spirals and irregulars is very steep. The Sm-Im luminosity function is well fit by a Schechter function with M*=-18.79, alpha=-1.87, and phi*=0.6x10(exp -3) for M(sub z) less than or equal to -13. These galaxies are largely responsible for the excess at the faint end of the general CfA luminosity function. The abundance of intrinsically faint, blue galaxies nearby affects the interpretation of deep number counts. The dwarf population increases the expected counts at B=25 in a no-evolution, q(sub 0)=0.05 model by a factor of two over standard no-evolution estimates. These dwarfs change the expected median redshift in deep redshift surveys by less than 10 percent . Thus the steep Sm-Im LF may contribute to the reconciliation of deep number counts with deep redshift surveys.

Cystic fibrosis liver disease - from diagnosis to risk factors.

PubMed

Ciucă, Ioana Mihaiela; Pop, Liviu; Tămaş, Liviu; Tăban, Sorina

2014-01-01

Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency, meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases. Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer.

PubMed

Guttery, David S; Page, Karen; Hills, Allison; Woodley, Laura; Marchese, Stephanie D; Rghebi, Basma; Hastings, Robert K; Luo, Jinli; Pringle, J Howard; Stebbing, Justin; Coombes, R Charles; Ali, Simak; Shaw, Jacqueline A

2015-07-01

Activating mutations in the estrogen receptor 1 (ESR1) gene are acquired on treatment and can drive resistance to endocrine therapy. Because of the spatial and temporal limitations of needle core biopsies, our goal was to develop a highly sensitive, less invasive method of detecting activating ESR1 mutations via circulating cell-free DNA (cfDNA) and tumor cells as a "liquid biopsy." We developed a targeted 23-amplicon next-generation sequencing (NGS) panel for detection of hot-spot mutations in ESR1, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tumor protein p53 (TP53), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 2 (FGFR2) in 48 patients with estrogen receptor-α-positive metastatic breast cancer who were receiving systemic therapy. Selected mutations were validated using droplet digital PCR (ddPCR). Nine baseline cfDNA samples had an ESR1 mutation. NGS detected 3 activating mutations in ESR1, and 3 hot-spot mutations in PIK3CA, and 3 in TP53 in baseline cfDNA, and the ESR1 p.D538G mutation in 1 matched circulating tumor cell sample. ddPCR analysis was more sensitive than NGS and identified 6 additional baseline cfDNA samples with the ESR1 p.D538G mutation at a frequency of <1%. In serial blood samples from 11 patients, 4 showed changes in cfDNA, 2 with emergence of a mutation in ESR1. We also detected a low frequency ESR1 mutation (1.3%) in cfDNA of 1 primary patient who was thought to have metastatic disease but was clear by scans. Early identification of ESR1 mutations by liquid biopsy might allow for cessation of ineffective endocrine therapies and switching to other treatments, without the need for tissue biopsy and before the emergence of metastatic disease. © 2015 American Association for Clinical Chemistry.

Continuous alternating inhaled antibiotic therapy in CF: A single center retrospective analysis.

PubMed

Van de Kerkhove, C; Goeminne, P C; Kicinski, M; Nawrot, T S; Lorent, N; Van Bleyenbergh, P; De Boeck, K; Dupont, L J

2016-11-01

The efficacy of inhaled antibiotics to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been well established. Few data are available on the value of continuous alternating inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management of CF. To investigate the effect of CAIT on clinical outcome in adult CF patients treated at the University Hospital Leuven. Patients with a documented CF diagnosis who received inhaled antibiotics between March 2010 and January 2015 were retrospectively evaluated. In patients receiving CAIT patient characteristics, recorded spirometry data and number of IV antibiotic days were collected retrospectively at fixed time intervals, from 6months before to one year after the start of the 2nd inhaled antibiotic. For patients on inhaled antibiotic monotherapy (IAMT), the same data were obtained at similar intervals during the study period. A total of 49 of 89 patients using chronic inhaled antibiotic therapy received CAIT. Patients receiving CAIT had a lower baseline FEV 1 and were more likely to be homozygous for F508del compared to patients receiving IAMT. FEV 1 deteriorated on average by a factor of 0.904 per year (95% CI: 0.851-0.960) prior to the start of CAIT. The initiation of CAIT was associated with an average improvement in FEV 1 by a factor of 1.148 per year (95% CI: 1.068-1.236, p=0.0002). The analysis of specific types of antibiotics revealed evidence of positive effects of adding COLI to TOBI and COLI to AZLI. We found no effect of the initiation of CAIT on the number of IV antibiotic days (p=0.80). CF patients with more advanced lung disease are more likely to receive CAIT. In this patient group, CAIT was associated with a significant improvement in FEV 1 . Further data are warranted to identify the value of CAIT. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Rapid point-of-care testing for epidermal growth factor receptor gene mutations in patients with lung cancer using cell-free DNA from cytology specimen supernatants.

PubMed

Asaka, Shiho; Yoshizawa, Akihiko; Saito, Kazusa; Kobayashi, Yukihiro; Yamamoto, Hiroshi; Negishi, Tatsuya; Nakata, Rie; Matsuda, Kazuyuki; Yamaguchi, Akemi; Honda, Takayuki

2018-06-01

Epidermal growth factor receptor (EGFR) mutations are associated with responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). Our previous study revealed a rapid point-of-care system for detecting EGFR mutations. This system analyzes cell pellets from cytology specimens using droplet-polymerase chain reaction (d-PCR), and has a reaction time of 10 min. The present study aimed to validate the performance of the EGFR d-PCR assay using cell-free DNA (cfDNA) from supernatants obtained from cytology specimens. Assay results from cfDNA supernatant analyses were compared with those from cell pellets for 90 patients who were clinically diagnosed with, or suspected of having, lung cancer (80 bronchial lavage fluid samples, nine pleural effusion samples and one spinal fluid sample). EGFR mutations were identified in 12 and 15 cases using cfDNA supernatants and cell pellets, respectively. The concordance rates between cfDNA-supernatant and cell‑pellet assay results were 96.7% [kappa coefficient (K)=0.87], 98.9% (K=0.94), 98.9% (K=0.79) and 98.9% (K=0.79) for total EGFR mutations, L858R, E746_A750del and T790M, respectively. All 15 patients with EGFR mutation-positive results, as determined by EGFR d-PCR assay using cfDNA supernatants or cell pellets, also displayed positive results by conventional EGFR assays using tumor tissue or cytology specimens. Notably, EGFR mutations were even detected in five cfDNA supernatants for which the cytological diagnoses of the corresponding cell pellets were 'suspicious for malignancy', 'atypical' or 'negative for malignancy.' In conclusion, this rapid point-of-care system may be considered a promising novel screening method that may enable patients with NSCLC to receive EGFR-TKI therapy more rapidly, whilst also reserving cell pellets for additional morphological and molecular analyses.

Factors Affecting Parent-Child Relationships One Year After Positive Newborn Screening for Cystic Fibrosis or Congenital Hypothyroidism

PubMed Central

Tluczek, Audrey; Clark, Roseanne; McKechnie, Anne Chevalier; Brown, Roger L.

2014-01-01

Objective Examine factors that mediate parent-infant relationships 12 months after positive newborn screening (NBS). Method We examined effects of infant diagnosis, parents’ perceptions of child vulnerability and child attachment, parental depression and anxiety on parent-infant feeding interactions for 131 mothers and 118 fathers of 131 infants whose NBS and diagnostics confirmed cystic fibrosis (CF, n=23), congenital hypothyroidism (CH, n=35), CF carrier status (CF-C, n=38), or healthy, normal NBS (H, n=35). Results Separate composite indicator structural equation models for mothers and fathers showed neonatal diagnosis was not associated with increased anxiety or depression. In comparison to the H group, CF group parents reported higher perceptions of child vulnerability (p< 0.001, p=0.002); and CF-C group fathers viewed their children as more attached (p=0.021). High maternal perception of child vulnerability was associated with low perceptions of child attachment (p=0.001) which was associated with task-oriented feeding behavior (p=0.016, p=0.029). Parental task-oriented feeding behavior was associated with less positive (p< 0.001, p< 0.001) and more negative interactions (p< 0.001, p= 0.001) with their infants. High paternal perception of child vulnerability was associated with negative parent interactions (p< 0.001). High parental affective involvement and verbalization was associated with high infant affective expressiveness, communicative skills, and social responsiveness (mothers’ p< 0.001, fathers’ p< 0.001). High parental negative affect and/or inconsistent and intrusive behavior was associated with infant dysregulation and irritability (mothers’ p< 0.001, fathers’ p< 0.001). Conclusion The severity of conditions identified through NBS can affect parents’ perceptions of their child’s vulnerability and attachment. Infant feeding problems in the context of chronic health conditions, like CF, could represent signs of more deeply rooted concerns regarding the parent-child relationship that merit additional clinical evaluation. PMID:25493463

Multivariate statistical analysis of heavy metal concentration in soils of Yelagiri Hills, Tamilnadu, India--spectroscopical approach.

PubMed

Chandrasekaran, A; Ravisankar, R; Harikrishnan, N; Satapathy, K K; Prasad, M V R; Kanagasabapathy, K V

2015-02-25

Anthropogenic activities increase the accumulation of heavy metals in the soil environment. Soil pollution significantly reduces environmental quality and affects the human health. In the present study soil samples were collected at different locations of Yelagiri Hills, Tamilnadu, India for heavy metal analysis. The samples were analyzed for twelve selected heavy metals (Mg, Al, K, Ca, Ti, Fe, V, Cr, Mn, Co, Ni and Zn) using energy dispersive X-ray fluorescence (EDXRF) spectroscopy. Heavy metals concentration in soil were investigated using enrichment factor (EF), geo-accumulation index (Igeo), contamination factor (CF) and pollution load index (PLI) to determine metal accumulation, distribution and its pollution status. Heavy metal toxicity risk was assessed using soil quality guidelines (SQGs) given by target and intervention values of Dutch soil standards. The concentration of Ni, Co, Zn, Cr, Mn, Fe, Ti, K, Al, Mg were mainly controlled by natural sources. Multivariate statistical methods such as correlation matrix, principal component analysis and cluster analysis were applied for the identification of heavy metal sources (anthropogenic/natural origin). Geo-statistical methods such as kirging identified hot spots of metal contamination in road areas influenced mainly by presence of natural rocks. Copyright © 2014 Elsevier B.V. All rights reserved.

Improved yield and Zn accumulation for rice grain by Zn fertilization and optimized water management.

PubMed

Wang, Yu-yan; Wei, Yan-yan; Dong, Lan-xue; Lu, Ling-li; Feng, Ying; Zhang, Jie; Pan, Feng-shan; Yang, Xiao-e

2014-04-01

Zinc (Zn) deficiency and water scarcity are major challenges in rice (Oryza sativa L.) under an intensive rice production system. This study aims to investigate the impact of water-saving management and different Zn fertilization source (ZnSO4 and Zn-EDTA) regimes on grain yield and Zn accumulation in rice grain. Different water managements, continuous flooding (CF), and alternate wetting and drying (AWD) were applied during the rice growing season. Compared with CF, the AWD regime significantly increased grain yield and Zn concentrations in both brown rice and polished rice. Grain yield of genotypes (Nipponbare and Jiaxing27), on the average, was increased by 11.4%, and grain Zn concentration by 3.9% when compared with those under a CF regime. Zn fertilization significantly increased Zn density in polished rice, with a more pronounced effect of ZnSO4 being observed as compared with Zn-EDTA, especially under an AWD regime. Decreased phytic acid content and molar ratio of phytic acid to Zn were also noted in rice grains with Zn fertilization. The above results demonstrated that water management of AWD combined with ZnSO4 fertilization was an effective agricultural practice to elevate grain yield and increase Zn accumulation and bioavailability in rice grains.

A novel strategy for highly efficient isolation and analysis of circulating tumor-specific cell-free DNA from lung cancer patients using a reusable conducting polymer nanostructure.

PubMed

Lee, HyungJae; Jeon, SeungHyun; Seo, Jin-Suck; Goh, Sung-Ho; Han, Ji-Youn; Cho, Youngnam

2016-09-01

We have developed a reusable nanostructured polypyrrole nanochip and demonstrated its use in the electric field-mediated recovery of circulating cell-free DNA (cfDNA) from the plasma of lung cancer patients. Although cfDNA has been recognized and widely studied as a versatile and promising biomarker for the diagnosis and prognosis of cancers, the lack of efficient strategies to directly isolate cfDNA from the plasma has become a great hindrance to its potential clinical use. As a proof-of-concept study, we demonstrated a technique for the rapid and efficient isolation of cfDNA with high yield and purity. In particular, the synergistic effects of the electro-activity and the nanostructured features of the polypyrrole polymer enabled repeated retrieval of cfDNA using a single platform. Moreover, polypyrrole nanochip facilitated the amplification of tumor-specific DNA fragments from the plasma samples of patients with lung cancer characterized by mutations in exons 21 of the epidermal growth factor receptor gene (EGFR). Overall, the proposed polypyrrole nanochip has enormous potential for industrial and clinical applications with significantly enhanced efficiency in the recovery of tumor-associated circulating cfDNA. This may ultimately contribute to more robust and reliable evaluation of gene mutations in peripheral blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets.

PubMed

Pabari, Ritesh M; Ramtoola, Zebunnissa

2012-07-01

A two factor, three level (3(2)) face centred, central composite design (CCD) was applied to investigate the main and interaction effects of tablet diameter and compression force (CF) on hardness, disintegration time (DT) and porosity of mannitol based orodispersible tablets (ODTs). Tablet diameters of 10, 13 and 15 mm, and CF of 10, 15 and 20 kN were studied. Results of multiple linear regression analysis show that both the tablet diameter and CF influence tablet characteristics. A negative value of regression coefficient for tablet diameter showed an inverse relationship with hardness and DT. A positive value of regression coefficient for CF indicated an increase in hardness and DT with increasing CF as a result of the decrease in tablet porosity. Interestingly, at the larger tablet diameter of 15 mm, while hardness increased and porosity decreased with an increase in CF, the DT was resistant to change. The optimised combination was a tablet of 15 mm diameter compressed at 15 kN showing a rapid DT of 37.7s and high hardness of 71.4N. Using these parameters, ODTs containing ibuprofen showed no significant change in DT (ANOVA; p>0.05) irrespective of the hydrophobicity of the ibuprofen. Copyright © 2012 Elsevier B.V. All rights reserved.

Joint carbon footprint assessment and data envelopment analysis for the reduction of greenhouse gas emissions in agriculture production.

PubMed

Rebolledo-Leiva, Ricardo; Angulo-Meza, Lidia; Iriarte, Alfredo; González-Araya, Marcela C

2017-09-01

Operations management tools are critical in the process of evaluating and implementing action towards a low carbon production. Currently, a sustainable production implies both an efficient resource use and the obligation to meet targets for reducing greenhouse gas (GHG) emissions. The carbon footprint (CF) tool allows estimating the overall amount of GHG emissions associated with a product or activity throughout its life cycle. In this paper, we propose a four-step method for a joint use of CF assessment and Data Envelopment Analysis (DEA). Following the eco-efficiency definition, which is the delivery of goods using fewer resources and with decreasing environmental impact, we use an output oriented DEA model to maximize production and reduce CF, taking into account simultaneously the economic and ecological perspectives. In another step, we stablish targets for the contributing CF factors in order to achieve CF reduction. The proposed method was applied to assess the eco-efficiency of five organic blueberry orchards throughout three growing seasons. The results show that this method is a practical tool for determining eco-efficiency and reducing GHG emissions. Copyright © 2017 Elsevier B.V. All rights reserved.

CF60 Concrete Composition Design and Application on Fudiankou Xijiang Super Large Bridge

NASA Astrophysics Data System (ADS)

Qiu, Yi Mei; Wen, Sen Yuan; Chen, Jun Xiang

2018-06-01

Guangxi Wuzhou City Ring Road Fudiankou Xijiang super large bridge CF60 concrete is a new multi-phase composite high-performance concrete, this paper for the Fudiankou Xijiang bridge structure and characteristics of the project, in accordance with the principle of local materials and technical specification requirements, combined with the site conditions of CF60 engineering high performance concrete component materials, proportion and the technical performance, quantify the main physical and mechanical performance index. Analysis main influencing factors of the technical indicators, reasonable adjustment of concrete mix design parameters, and the use of technical means of admixture and multi-function composite admixture of concrete, obtain the optimal proportion of good work, process, mechanical properties stability and durability of engineering properties, recommend and verification of concrete mix; to explore the CF60 high performance concrete Soil in the Fudiankou Xijiang bridge application technology, detection and tracking the quality of concrete construction, concrete structure during the construction of the key technology and control points is proposed, evaluation of CF60 high performance concrete in the actual engineering application effect and benefit to ensure engineering quality of bridge structure and service life, and super long span bridge engineering construction to provide basis and reference.

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

PubMed

Fernandez Fernandez, Elena; de Santi, Chiara; De Rose, Virginia; Greene, Catherine M

2018-05-11

Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert Commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

Altered Sputum Microstructure as a Marker of Airway Obstruction in Cystic Fibrosis Patients

NASA Astrophysics Data System (ADS)

Duncan, Gregg; Jung, James; West, Natalie; Boyle, Michael; Suk, Jung Soo; Hanes, Justin

In the lungs of cystic fibrosis (CF) patients, highly viscoelastic mucus remains stagnant in the lung leading to obstructed airways prone to recurrent infections. Bulk-fluid rheological measurement is primarily used to assess the pathological features of mucus. However, this approach is limited in detecting microscopic properties on the length scale of pathogens and immune cells. We have shown in prior work based on the transport of muco-inert nanoparticles (MIP) in CF sputum that patients can carry significantly different microstructural properties. In this study, we aimed to determine the factors leading to variations between patients in sputum microstructure and their clinical implications. The microrheological properties of CF sputum were measured using multi-particle tracking experiments of MIP. MIP were made by grafting polyethylene glycol onto the surface of polystyrene nanoparticles which prior work has shown prevents adhesion to CF sputum. Biochemical analyses show that sputum microstructure was significantly altered by elevated mucin and DNA content. Reduction in sputum pore size is characteristic of patients with obstructed airways as indicated by measured pulmonary function tests. Our microstructural read-out may serve as a novel biomarker for CF.

Trends in the epidemiological aspects and mortality of alcoholic liver disease in Korea in the decade between 2000 and 2009.

PubMed

Bang, Hyung-Ae; Kwon, Young-Hwan; Lee, Myeong-Jin; Lee, Won-Chang

2015-02-01

Alcohol consumption and related alcohol liver disease (ALD) have substantially increased in Korea during the last decade. The objective of this study was to evaluate the trends in the epidemiological aspects and mortality rate (MR) of Korea in the decade between 2000 and 2009. The raw data analyzed in this study were obtained from the website of "the ALD" managed by Korea Center for Disease Control and Prevention (KCDC), Korea Public Health Association (KPHA), and statistics website of Statistics Korea. The data analyses were performed using Excel 2007 statistical software (Microsoft Corp., USA). The amount of alcohol-consumption-per-capita-per-year (ACCY) in Korea was 8.38 L in 2000 and 8.54 L in 2009. The most taken alcoholic beverage was soju, followed by beer. There were a total of 1,403 case-fatalities (CF) with an MR of 2.98 per 100,000 populations of ALD in 2000, while a total of 3,588 CF with an MR of 7.21 in 2009 (P < 0.01). The CF and MR of ALD in males were significantly higher than those in females (P < 0.01). In over 40-year-old age groups, the CF and MR were significantly increased (P < 0.01). Moreover, occupational classification revealed that the mistress/students/jobless (MSJ) were the most risky group. The comparison of overall CF and MR of ALD by six key classifications (International Classification of Diseases (ICD)) showed that alcoholic cirrhosis (229 CF and 16.3%) in 2000 tended to be increased in 2009 (2,803 CF and 78.1%), while alcoholic fibrosis and sclerosis (607 CF and 43.3%) in 2000 significantly decreased in 2009 (120 CF and 3.3%), respectively. ALD is one of the most severe diseases in Korea, as indicated by its high CF and MR in this study. As over-consumption of alcoholic beverages is relatively common in Korea, more efforts should be made toward prevention of ALD by raising awareness of the risk factors of ALD by public health education.

Trends in the Epidemiological Aspects and Mortality of Alcoholic Liver Disease in Korea in the Decade Between 2000 and 2009

PubMed Central

Bang, Hyung-Ae; Kwon, Young-Hwan; Lee, Myeong-Jin; Lee, Won-Chang

2015-01-01

Background Alcohol consumption and related alcohol liver disease (ALD) have substantially increased in Korea during the last decade. The objective of this study was to evaluate the trends in the epidemiological aspects and mortality rate (MR) of Korea in the decade between 2000 and 2009. Methods The raw data analyzed in this study were obtained from the website of “the ALD” managed by Korea Center for Disease Control and Prevention (KCDC), Korea Public Health Association (KPHA), and statistics website of Statistics Korea. The data analyses were performed using Excel 2007 statistical software (Microsoft Corp., USA). Results The amount of alcohol-consumption-per-capita-per-year (ACCY) in Korea was 8.38 L in 2000 and 8.54 L in 2009. The most taken alcoholic beverage was soju, followed by beer. There were a total of 1,403 case-fatalities (CF) with an MR of 2.98 per 100,000 populations of ALD in 2000, while a total of 3,588 CF with an MR of 7.21 in 2009 (P < 0.01). The CF and MR of ALD in males were significantly higher than those in females (P < 0.01). In over 40-year-old age groups, the CF and MR were significantly increased (P < 0.01). Moreover, occupational classification revealed that the mistress/students/jobless (MSJ) were the most risky group. The comparison of overall CF and MR of ALD by six key classifications (International Classification of Diseases (ICD)) showed that alcoholic cirrhosis (229 CF and 16.3%) in 2000 tended to be increased in 2009 (2,803 CF and 78.1%), while alcoholic fibrosis and sclerosis (607 CF and 43.3%) in 2000 significantly decreased in 2009 (120 CF and 3.3%), respectively. Conclusion ALD is one of the most severe diseases in Korea, as indicated by its high CF and MR in this study. As over-consumption of alcoholic beverages is relatively common in Korea, more efforts should be made toward prevention of ALD by raising awareness of the risk factors of ALD by public health education. PMID:25436025

Behavior of a Liquid Bridge between Nonparallel Hydrophobic Surfaces.

PubMed

Ataei, Mohammadmehdi; Chen, Huanchen; Amirfazli, Alidad

2017-12-26

When a liquid bridge is formed between two nonparallel identical surfaces, it can move along the surfaces. Literature indicates that the direction of bridge movement is governed by the wettability of surfaces. When the surfaces are hydrophilic, the motion of the bridge is always toward the cusp (intersection of the plane of the two bounding surfaces). On the other hand, the movement is hitherto thought to be always pointing away from the cusp when the surfaces are hydrophobic. In this study, through experiments, numerical simulations, and analytical reasoning, we demonstrate that for hydrophobic surfaces, wettability is not the only factor determining the direction of the motion. A new geometrical parameter, i.e., confinement (cf), was defined as the ratio of the distance of the farthest contact point of the bridge to the cusp, and that of the closest contact point to the cusp. The direction of the motion depends on the amount of confinement (cf). When the distance between the surfaces is large (resulting in a small cf), the bridge tends to move toward the cusp through a pinning/depinning mechanism of contact lines. When the distance between the surfaces is small (large cf), the bridge tends to move away from the cusp. For a specific system, a maximum cf value (cf max ) exists. A sliding behavior (i.e., simultaneous advancing on the wider side and receding on the narrower side) can also be seen when a liquid bridge is compressed such that the cf exceeds the cf max . Contact angle hysteresis (CAH) is identified as an underpinning phenomenon that together with cf fundamentally explains the movement of a trapped liquid between two hydrophobic surfaces. If there is no CAH, however, i.e., the case of ideal hydrophobic surfaces, the cf will be a constant; we show that the bridge slides toward the cusp when it is stretched, while it slides away from the cusp when it is compressed (note sliding motion is different from motion due to pinning/depinning mechanism of contact lines). As such, the displacement is only related to geometrical parameters such as the amount of compression (or stretching) and the dihedral angle between the surfaces.

A Continuous Flow Column Study of the Anaerobic Transformation of a CAH Mixture of Tetrachloroethene and Carbon Tetrachloride Using Formate as an Electron Donor

NASA Astrophysics Data System (ADS)

Semprini, L.; Azizian, M. F.; Kim, Y.

2011-12-01

Many groundwater sites are contaminated with mixtures of chlorinated aliphatic hydrocarbons (CAHs) that represent a challenge when biological remediation processes are being considered. This is especially challenging when high concentrations of CAHs are present.Trichloromethane (CF), for example, has been observed to inhibit and potentially exert toxicity on reductive dehalogenation of tetrachloroethene (PCE) and trichloroethene (TCE). Results will be presented from a continuous flow column study where the simultaneous transformation of PCE and carbon tetrachloride (CT) was achieved. The column was packed with a quartz sand and bioaugmented with the Evanite Culture (EV) that is capable of transforming PCE to ethene. The column was fed a synthetic groundwater that was amended with PCE to achieve an influent concentration near its solubility limit (0.10 mM) and formate (1.5 mM) that reacts to produce hydrogen as the ultimate electron donor. The column was operated for over 1600 days prior to the addition of CT. During this period PCE was transformed mainly to vinyl chloride (VC) and ethene (ETH) and minor amounts of cis-dichloroethene (cis-DCE) and TCE. The transformation extent achieved based on the column effluent concentrations ranged from about 50% ETH, 30% VC, and 20 cis-DCE up to 80% ETH and 20% VC. When the column was fed sulfate, it was completely transformed via sulfate reduction. Ferrous iron production from ferric iron reduction was observed early in the study. Acetate was also formed as a result of homoacetogenesis from hydrogen utilization. CT addition (0.015 mM) was started at 1600 days while PCE addition was continued. During the first 25 days of CT addition, CT concentrations gradually increased to 50% of the injection concentration and chloromethane (CM) and CF were observed as transformation products. CT concentrations then decreased with over 98% transformation achieved.CM was removed to below the detection limit and CF concentration decreases to about 0.003 mM, representing 20% of the CT transformed. Other transformation products have not been identified. Neither methane nor carbon monoxide have been detected as transformation products. The transformation of PCE to ethene actually improved after the addition of CT. Thus, neither CT nor CF are inhibiting the reductive dehalogenation of PCE. The improvement in PCE transformation extent coincided with an increase in the aqueous hydrogen concentration from 5 nM, prior to CT addition, to 150 nM after CT addition. This increase in hydrogen was associated with the inhibition in acetate production and the increase in formate concentrations from below detection to 1.0 mM after CT addition. The results indicate that there are likely benefits in adding formate to produce hydrogen when contaminants are present that can inhibit fermentation. The results from the column study are consistent with our observations in batch reactors using the EV culture.

High-resolution spectroscopy and global analysis of CF4 rovibrational bands to model its atmospheric absorption

NASA Astrophysics Data System (ADS)

Carlos, M.; Gruson, O.; Richard, C.; Boudon, V.; Rotger, M.; Thomas, X.; Maul, C.; Sydow, C.; Domanskaya, A.; Georges, R.; Soulard, P.; Pirali, O.; Goubet, M.; Asselin, P.; Huet, T. R.

2017-11-01

CF4, or tetrafluoromethane, is a chemically inert and strongly absorbing greenhouse gas, mainly of anthropogenic origin. In order to monitor and reduce its atmospheric emissions and concentration, it is thus necessary to obtain an accurate model of its infrared absorption. Such models allow opacity calculations for radiative transfer atmospheric models. In the present work, we perform a global analysis (divided into two distinct fitting schemes) of 17 rovibrational bands of CF4. This gives a reliable model of many of its lower rovibrational levels and allows the calculation of the infrared absorption in the strongly absorbing ν3 region (1283 cm-1 / 7.8 μm), including the main hot band, namely ν3 +ν2 -ν2 as well as ν3 +ν1 -ν1 ; we could also extrapolate the ν3 +ν4 -ν4 absorption. This represents almost 92% of the absorption at room temperature in this spectral region. A new accurate value of the C-F bond length is evaluated to re = 1.314860(21) Å. The present results have been used to update the HITRAN, GEISA and TFMeCaSDa (VAMDC) databases.

Fourier Transform Infrared Spectroscopy of CF4 on the GEC Reference Cell

NASA Technical Reports Server (NTRS)

Rao, M. V. V. S.; Sharma, S. P.; Meyyappan, M.; Cruden, Brett A.; Arnold, Jim (Technical Monitor)

2001-01-01

Fourier Transform Infrared Spectroscopy (FTIR) has been used to characterize inductively coupled CF4 plasmas in a GEC Reference Cell in-situ In examining these FTIR spectra, several assumptions and approximations of FTIR analysis are addressed. This includes the density dependence of cross-sections, non-linear effects in the addition of overlapping bands and the effect of spatial variations in density and temperature, This analysis demonstrates that temperatures extracted from MR spectra may provide a poor estimate of the true neutral plasma temperature. The FTIR spectra are dominated by unreacted CF, accounting for 40-60% of the gas products. The amount of CF4 consumption is found to have a marked dependence on power, and is nearly independent of pressure in the range of 10-50 mtorr. Small amounts of C2F6 are observed at low power. Also observed are etching products from the quartz window SiF4 COF2 and CO which occur in approximately equal ratios and together account for less than 10% of the gas. The concentrations of these species are nearly independent of pressure. CFx radicals are below the detection limit of this apparatus (approx. 1012/cc).

Mechanical property degradation and microstructural evolution of cast austenitic stainless steels under short-term thermal aging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lach, Timothy G.; Byun, Thak Sang; Leonard, Keith J.

Mechanical testing and microstructural characterization were performed on short-term thermally aged cast austenitic stainless steels (CASS) to understand the severity and mechanisms of thermal-aging degradation experienced during extended operation of light water reactor (LWR) coolant systems. Four CASS materials – CF3, CF3M, CF8, and CF8M – were thermally aged for 1500 hours at 290 °C, 330 °C, 360 °C, and 400 °C. All four alloys experienced insignificant change in strength and ductility properties but a significant reduction in absorbed impact energy. The primary microstructural and compositional changes during thermal aging were spinodal decomposition of the δ-ferrite into α/ α`, precipitationmore » of G-phase in the δ-ferrite, segregation of solute to the austenite/ ferrite interphase boundary, and growth of M23C6 carbides on the austenite/ferrite interphase boundary. These changes were shown to be highly dependent on chemical composition, particularly the concentration of C and Mo, and aging temperature. A comprehensive model is being developed to correlate the microstructural evolution with mechanical behavior and simulation for predictive evaluations of LWR coolant system components.« less