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1.
Elif Erdem Ibrahim Inan Harbiyeli Hazal Boral Macit Ilkit Meltem Yagmur Reha Ersoz 《Mycopathologia》2018,183(3):521-527
Purpose
To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.Design
Retrospective case series in a tertiary university hospital.Participants
CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.Methods
The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.Main Outcome Measures
Grade of the corneal infection.Results
Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).Conclusions
The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.2.
Clare B. O’Donovan Marianne C. Walsh Hannah Forster Clara Woolhead Carlos Celis-Morales Rosalind Fallaize Anna L. Macready Cyril F. M. Marsaux Santiago Navas-Carretero Rodrigo San-Cristobal Silvia Kolossa Christina Mavrogianni Christina P. Lambrinou George Moschonis Magdalena Godlewska Agnieszka Surwillo Jildau Bouwman Keith Grimaldi Iwona Traczyk Christian A. Drevon Hannelore Daniel Yannis Manios J. Alfredo Martinez Wim H. M. Saris Julie A. Lovegrove John C. Mathers Michael J. Gibney Lorraine Brennan Eileen R. Gibney 《Genes & nutrition》2016,11(1):25
Background
It is hypothesised that individuals with knowledge of their genetic risk are more likely to make health-promoting dietary and lifestyle changes. The present study aims to test this hypothesis using data from the Food4Me study. This was a 6-month Internet-based randomised controlled trial conducted across seven centres in Europe where individuals received either general healthy eating advice or varying levels of personalised nutrition advice. Participants who received genotype-based personalised advice were informed whether they had the risk (CT/TT) (n?=?178) or non-risk (CC) (n?=?141) alleles of the methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular health and the importance of a sufficient intake of folate. General linear model analysis was used to assess changes in folate intake between the MTHFR risk, MTHFR non-risk and control groups from baseline to month 6 of the intervention.Results
There were no differences between the groups for age, gender or BMI. However, there was a significant difference in country distribution between the groups (p?=?0.010). Baseline folate intakes were 412?±?172, 391?±?190 and 410?±?186 μg per 10 MJ for the risk, non-risk and control groups, respectively. There were no significant differences between the three groups in terms of changes in folate intakes from baseline to month 6. Similarly, there were no changes in reported intake of food groups high in folate.Conclusions
These results suggest that knowledge of MTHFR 677C?→?T genotype did not improve folate intake in participants with the risk variant compared with those with the non-risk variant.Trial registration
ClinicalTrials.gov NCT015301393.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.4.
John M. Wentworth Naiara G. Bediaga Megan A. S. Penno Esther Bandala-Sanchez Komal N. Kanojia Konstantinos A. Kouremenos Jennifer J. Couper Leonard C. Harrison ENDIA Study Group 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):130
Background
Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.Method
Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.Results
Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.Conclusion
Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.5.
Dorothea Lesche Roland Geyer Daniel Lienhard Christos T. Nakas Gaëlle Diserens Peter Vermathen Alexander B. Leichtle 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):159
Background
Centrifugation is an indispensable procedure for plasma sample preparation, but applied conditions can vary between labs.Aim
Determine whether routinely used plasma centrifugation protocols (1500×g 10 min; 3000×g 5 min) influence non-targeted metabolomic analyses.Methods
Nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS) data were evaluated with sparse partial least squares discriminant analyses and compared with cell count measurements.Results
Besides significant differences in platelet count, we identified substantial alterations in NMR and HRMS data related to the different centrifugation protocols.Conclusion
Already minor differences in plasma centrifugation can significantly influence metabolomic patterns and potentially bias metabolomics studies.6.
Objectives
To evaluate the effects of dexamethasone on the aging of mesenchymal stem cells from human gingiva using next-generation sequencing.Results
Four mRNAs were upregulated and 12 were downregulated when the results of dexamethasone at 24 h were compared with the control at 24 h. Expressions of SIRT1 and IL6 were decreased in dexamethasone at 24 h but expression of EDN1 was increased.Conclusions
Application of dexamethasone reduced the expression of SIRT1 and IL6 but enhanced the expression of EDN1 of stem cells.7.
Andreas Entenmann Miriam Michel Bruno Ismer Roman Gebauer 《Biomedical engineering online》2017,16(1):139
Background
R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP–VS) may be observed during routine clinical practice.Objectives
The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP–VS intervals.Methods
Calculated AP–VS intervals were compared with those predicted by experienced pediatric cardiologist.Results
A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP–VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP–VS interval could not be predicted by experienced observers. In our newly proposed technique the AP–VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (? 0.4 ms/bpm) between the two extreme levels.Conclusions
Adjusting the AP–VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP–VS interval.8.
Masahito Uji Yukihiro Yokoyama Katsuya Ohbuchi Kazuaki Tsuchiya Chiharu Sadakane Chika Shimobori Masahiro Yamamoto Masato Nagino 《Metabolomics : Official journal of the Metabolomic Society》2017,13(12):155
Introduction
In patients with obstructive jaundice, biliary drainage sometimes fails to result in improvement. A pharmaceutical-grade choleretic herbal medicine, Inchinkoto (ICKT), has been proposed to exert auxiliary effects on biliary drainage; however, its effects are variable among patients.Objectives
The aim of this study is to explore serum biomarkers that are associated with pharmaceutical efficacy of ICKT.Methods
Obstructive jaundice patients who underwent external biliary decompression were enrolled (n?=?37). ICKT was given orally 3 times a day at daily dose of 7.5 g. Serum and bile samples were collected before, 3 h after, and 24 h after ICKT administration. The concentrations of total bilirubin, direct bilirubin, and total bile acid in bile specimens were measured. Metabolites in serum samples were comprehensively profiled using LC–MS/MS and GC–MS/MS. Pharmacokinetic analysis of major ICKT components was also performed.Results
ICKT administration significantly decreased serum ALT and increased bile volume after 24 h. The serum concentrations of ICKT components were not well correlated with the efficacy of ICKT. However, the ratio of 2-hydroxyisobutyric acid to arachidonic acid and the ratio of glutaric acid to niacinamide, exhibited good performance as biomarkers for the efficacy of ICKT on bile flow and ALT, respectively. Additionally, comprehensive correlation analysis revealed that serum glucuronic acid was highly correlated with serum total bilirubin, suggesting that this metabolite may be deeply involved in the pathogenesis of jaundice.Conclusions
The present study indicates that ICKT is efficacious and provides candidates for predicting ICKT efficacy. Further validation studies are warranted.9.
Matthew J. Roberts Clement W. K. Chow Martin Lavin Gregory K. Pierens Robert A. Gardiner 《Metabolomics : Official journal of the Metabolomic Society》2016,12(11):162
Introduction
Human seminal fluid (hSF) has been suggested as a biofluid suitable to characterise male reproductive organ pathology with metabolomics. However, various enzymatic processes, including phosphorylcholine hydrolysis mediated by prostatic acid phosphatase (PAP), cause unwanted metabolite variation that may complicate metabolomic analysis of fresh hSF samples.Objectives
To investigate the effects of PAP inhibition with tartrate.Methods
Using NMR spectroscopy, the kinetics of phosphorylcholine to choline hydrolysis was characterized in hSF samples from three subjects at different temperatures and tartrate concentrations. Principal components analysis was used to characterise the effects of tartrate and temperature on personal differences in metabolite profiles. Potential effects of tartrate on RNA quantification were also determined.Results
Metabolite profiles and the kinetics of phosphorylcholine degradation are reproducible in independent samples from three ostensibly normal subjects. Increasing concentrations of tartrate and refrigerated sample storage (279 K) resulted in greatly reduced reaction rates as judged by apparent rate constants. Multivariate statistical analysis showed that personal differences in metabolite profiles are not overshadowed by tartrate addition, which stabilises phosphorylcholine and choline concentrations. The tartrate signal also served as an internal concentration standard in the samples, allowing the determination of absolute metabolite concentrations in hSF. Furthermore, the presence of tartrate did not affect RNA expression analysis by qPCR.Conclusion
Based on these results we recommend as standard protocol for the collection of hSF samples, that 10 mM tartrate are added immediately to samples, followed by sample storage/handling at 277 K until clinical processing within 6 h to remove/inactivate enzymes and isolate metabolite supernatant and other cellular fractions.10.
Maria Isabel Ferreira Steve Green Nuno Conceição José-Enrique Fernández 《Plant and Soil》2018,425(1-2):21-41
Aims
In this study on hydraulic redistribution (HR) in roots, we aimed to use the calibrated average-gradient (CAG) heat-pulse method, the novelty being the use of a much narrower averaging window for the signal analysis, in order to achieve a more linear calibration curve, allowing the HR quantification.Methods
The study was conducted in 12 large roots of a rain-fed olive orchard, for 6 months without significant rain, when the predawn leaf water potential decreased to ?2.4 MPa, and immediately following the first autumn rains.Results
Detailed numerical modelling of the CAG method allowed verification of the response of the measurement system to a range of drivers, improving the linear range of the calibration response function, which has remained stable over the observations period. On average, reverse flow was observed during 30% of the summer nights and, in a conservative estimate, it increased to about 5% of total daily root flow before first autumn rain.Conclusions
Reverse flow accounted on average for 2.6% of the total daily root flow, enabling upper roots to stay active during the very dry late-summer period. In qualitative terms, our results confirm the CAG method as a reliable tool to identify reverse flow and quantify HR when it occurs.11.
Geoffrey A. Mueller Peter M. Thompson Eugene F. DeRose Thomas M. O’Connell Robert E. London 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):187
Background
Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated.Objective
This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine.Methods
An NMR metabolomics approach was used to measure metabolite concentrations in 26 pollen extracts. Pollen count data was analyzed from five cities to model exposure.Results
A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 µM) followed by trees (23 µM) and weeds (19 µM). Pollen count data showed that tree pollen was typically 5–10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to be only 1.1, 0.11, and 0.12 µg, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels.Conclusion
Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization.12.
Tilman Kühn Disorn Sookthai Ulrike Rolle-Kampczyk Wolfgang Otto Martin von Bergen Rudolf Kaaks Theron Johnson 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):184
Introduction
Plasma metabolites measured by metabolomics techniques have been shown to be associated with chronic disease risk in epidemiological studies. However, in most prospective studies metabolomic profiles can only be obtained at a single time point and data on intra-individual variation in metabolite levels over time are sparse.Objectives
Here, we evaluated the intra-individual variation in the concentrations of 177 metabolites over time using repeat blood samples of 104 adults (50% female).Methods
Blood samples were obtained at a baseline visit between 1994 and 1998 and during two further examinations 14 and 15 years later. Plasma metabolite levels were quantified by tandem mass spectrometry with the MetaDisIDQ? p180 Kit. Intra-individual variation was assessed by Spearman’s correlation coefficients (ρ).Results
Mid-term correlations over 1 year were good (ρ ≥ 0.7) for 5.1% and reasonable (ρ ≥ 0.4 < 0.7) for 61.0% of the metabolites, while long-term correlations over 15 years were good for 2.8% and reasonable for 27.1%. The strongest mid-term correlations between metabolite concentrations were observed for the acylcarnitine C3–OH (0.72) and metabolites from the amino acid/biogenic amine groups, i.e. creatinine (0.83), proline (0.79), lysine (0.77), isoleucine (0.76), and ornithine (0.74). C3–OH (0.78) as well as several amino acids/biogenic amines, i.e. ornithine (0.76), sarcosine (0.76), lysine (0.75), spermine (0.73), and glutamine (0.69) showed the strongest long-term correlations.Conclusions
The biological reproducibility of plasma concentrations of a majority of metabolites occurs reasonable over 1 year. In contrast, concentrations of many metabolites seem to be affected by substantial intra-individual variation over 15 years.13.
Objectives
To study the binding of pranlukast to hRKIP and its regulatory role in the Raf1/MEK/ERK signal pathway.Results
NMR and fluorescence experiments demonstrated hRKIP could bind pranlukast with a binding constant of 1016 mM?1. Residues (Y81, S109 and Y181) on the conserved ligand-binding pocket of hRKIP played a crucial role in binding pranlukast, and their mutations reduced the binding affinity more than 85 %. Furthermore, 25 μM pranlukast could up-regulate the ERK phosphorylation by about 17 %.Conclusion
Pranlukast may be used as a potential drug precursor for treating hRKIP involved diseases.14.
Transient expression of recombinant tissue plasminogen activator (rt-PA) gene in cucurbit plants using viral vector 总被引:1,自引:0,他引:1
Vahid Jalali Javaran Alireza Shafeinia Mokhtar Jalali Javaran Esmaeil Ghasemi Gojani Malihe Mirzaee 《Biotechnology letters》2017,39(4):607-612
Objective
To use a transient expression system to express a truncated human tissue plasminogen activator (K2S) gene in cucurbit plants.Results
The recombinant tissue plasminogen activator protein (K2S form) was expressed in active form in cucurbit plants. Its molecular weight was 43 kDa. The plant-derived rt-PA was determined using goat anti-rabbit antibody by western blotting. Among the infected lines, the highest expression of rt-PA was 62 ng/100 mg per leaf tissue as measured by ELISA. The enzymatic activity of the plant-derived rt-PA was 0.8 IU/ml.Conclusions
The K25 form of rt-PA was expressed for the first time using the viral expression system. Plant-derived rt-PA showed similar potency to commercially-available PA.15.
Background
The evidence on the use of the oral dimethyl-fumarate after the discontinuation of treatment with natalizumab in people with Multiple Sclerosis is still little. Natalizumab discontinuation may induce the recurrence or rebound of the clinical and neuroradiological disease activity. Currently no therapeutic approach has been established to abolish disease reactivation and rebound after natalizumab interruption.Case Presentation
We describe a case of a 21-year-old woman affected from a highly active relapsing-remitting Multiple Sclerosis who developed a clinical and radiological rebound 5 months after the last infusion of natalizumab, while she was being treated with dimethyl-fumarate 240 mg twice daily. She had received a bridge “therapy” with Cyclophosphamide before staring dimethyl-fumarate.Conclusion
We report on this case to stimulate further research to establish whether new current and future drugs available for multiple sclerosis are able to halt the disease rebound after the natalizumab interruption.16.
Shayne Mason A. Marceline Tutu van Furth Regan Solomons Ron A. Wevers Mari van Reenen Carolus J. Reinecke 《Metabolomics : Official journal of the Metabolomic Society》2016,12(7):110
Introduction
Tuberculous meningitis (TBM) is a severe manifestation of tuberculosis, presenting with high morbidity and mortality in children. Existing diagnostic methods for TBM are invasive and time-consuming and the need for highly sensitive and selective diagnosis remains high on the TBM agenda.Objective
Our aim was to exploit metabolomics as an approach to identify metabolites as potential diagnostic predictors for children with TBM through a non-invasive means.Methods
Urine samples selected for this study were from three paediatric groups: patients with confirmed TBM (n = 12), patients clinically suspected with TBM but later confirmed to be negative (n = 19) and age-matched controls (n = 29). Metabolomics data were generated through gas chromatography–mass spectrometry analysis and important metabolites were identified according to standard statistical procedures used for metabolomics data.Results
A global metabolite profile that characterized TBM was developed from the data, reflecting the host and microbial responses. Nine different logistic regression models were fitted to selected metabolites for the best combination as predictors for TBM. Four metabolites—methylcitric, 2-ketoglutaric, quinolinic and 4-hydroxyhippuric acids—showed excellent diagnostic ability and provided prognostic insight into our TBM patients.Conclusions
This study is the first to illustrate holistically the metabolic complexity of TBM and provided proof-of-concept that a biosignature of urinary metabolites can be defined for non-invasive diagnosis and prognosis of paediatric TBM patients. The biosignature should be developed and validated through future prospective studies to generate a medical algorithm for diagnosis in the initial stages of the disease and for monitoring of treatment strategies.17.
P. J. P. M. Cuijpers G. Bookelman W. Kicken W. de Vries A. P. M. Gorgels 《Netherlands heart journal》2016,24(7-8):456-461
Background
Integrating cardiopulmonary resuscitation (CPR) training in secondary schools will increase the number of potential CPR providers. However, currently too few certified instructors are available for this purpose. Training medical students and physical education student teachers to become CPR instructors could decrease this shortage.Aim
Examine whether medical students and physical education student teachers can provide CPR training for secondary school pupils as well as (i.?e., non-inferior to) registered nurses.Methods
A total of 144 secondary school pupils were randomly assigned to CPR training by a registered nurse (n = 12), a medical student (n = 17) or a physical education student teacher (n = 15). CPR performance was assessed after training and after eight weeks in a simulated cardiac arrest scenario on a resuscitation manikin, using manikin software and video recordings.Results
No significant differences were found between the groups on the overall Cardiff Test scores and the correctness of the CPR techniques during the post-training and retention test. All pupils showed sufficient CPR competence, even after eight weeks.Conclusion
Training by medical students or physical education student teachers is non-inferior to training by a registered nurse, suggesting that school teachers, student teachers and medical students can be recruited for CPR training in secondary schools.18.
Stephanie Blindenbach Jisca W. F. A. Vrancken Hans van der Zeijden Herre J. Reesink Folkert Brijker Martin Smalbrugge Elizabeth M. Wattel 《Tijdschrift voor gerontologie en geriatrie》2017,48(3):112-120
Introduction
Frail COPD patients are frequently not accepted for regular pulmonary rehabilitation programs due to low physical condition and functional limitations. Rehabilitation programs in nursing homes for geriatric patients with COPD have been developed. The effects of such programs are largely unknown.Aims
To assess the course of COPD-related hospital admissions and exercise tolerance in a cohort of frail COPD patients participating in geriatric COPD rehabilitation.Methods
Retrospective observational study with a follow up of 12 months after discharge from rehabilitation. COPD related hospital admission days were measured in the year before and after participating rehabilitation. Exercise tolerance was measured by the six minute walk test (6MWT) at admission and at discharge from rehabilitation.Results
Fifty-eight participants accomplished the rehabilitation program. Twelve patients died in the first year after discharge. The median number of hospital admission days in the year before participating rehabilitation was 21 (IQR 10–33). The first year after discharge this was decreased to a median of 6 (IQR 0–12). The 6MWT increased from 194 (SD 85) meters at admission to 274 (SD 95) meters at discharge (mean difference 80 m, SD 72; p < 0.05).Conclusions
Geriatric COPD rehabilitation in a nursing home setting seems to reduce hospital admissions in frail COPD patients and to increase exercise tolerance.19.
Liang Guo Ji Chen Eike Luedeling Jin-Sheng He Jimin Cheng Zhongming Wen Changhui Peng 《Plant and Soil》2018,425(1-2):177-188
Aims
The response of vegetation productivity to global warming is becoming a worldwide concern. While most reports on responses to warming trends are based on measured increases in air temperature, few studies have evaluated long-term variation in soil temperature and its impacts on vegetation productivity. Such impacts are especially important for high-latitude or high-altitude regions, where low temperature is recognized as the most critical limitation for plant growth.Methods
We used Partial Least Squares regression to correlate long-term aboveground net primary productivity (ANPP) data of an alpine grassland on the Qinghai-Tibetan Plateau with daily air and soil temperatures during 1997–2011. We also analyzed temporal trends for air temperature and soil temperature at different depths.Results
Soil temperatures have steadily increased at a rate of 0.4–0.9 °C per decade, whereas air temperatures showed no significant trend between 1997 and 2011. While temperature increases during the growing season (May–August) promoted aboveground productivity, warming before the growing season (March–April) had a negative effect on productivity. The negative effect was amplified in the soil layers, especially at 15 cm depth, where variation in aboveground productivity was dominated by early-spring soil warming, rather than by increasing temperature during the growing season.Conclusions
Future warming, especially in winter and spring, may further reduce soil water availability in early spring, which may slow down or even reverse the increases in grassland aboveground productivity that have widely been reported on the Qinghai-Tibetan Plateau.20.
Mark Daley Greg Dekaban Robert Bartha Arthur Brown Tanya Charyk Stewart Timothy Doherty Lisa Fischer Jeff Holmes Ravi S. Menon C. Anthony Rupar J. Kevin Shoemaker Douglas D. Fraser 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):185