We compared the validity of a semiquantitative food-frequency questionnaire in assessing intakes of macronutrients (absolute amounts and percentages of energy) by 19 subjects fed natural-food diets ...of known composition. In small subsets (n = 5 or 6), we also tested 3-d diet records.
The objective of this study was to investigate the efficacy of food-frequency questionnaires and diet records in subjects fed natural-food diets of known composition.
Each subject consumed 3 different diets for >/=6 wk and self-reported his or her food intake by using a food-frequency questionnaire and a diet record. The diets varied in their chemically analyzed contents of fat (15-35% energy), saturated fat (5-14%), monounsaturated fat (5-14.5%), polyunsaturated fat (2.5-10.5%), carbohydrate (49-68%), and cholesterol (108-348 mg/d).
The food-frequency questionnaire significantly underestimated fat, saturated fat, monounsaturated fat, and protein intakes and significantly overestimated carbohydrate intake with the high-fat diet. The percentage of energy from fat was significantly underestimated for the high-fat diet and significantly overestimated for the very-low-fat diet. Estimates from the food-frequency questionnaire differed significantly from actual intakes for fat (absolute and percentage), saturated fat (absolute and percentage), monounsaturated fat (absolute and percentage), and protein (percentage) in the high-fat diet and for polyunsaturated fat (absolute and percentage), saturated fat (percentage), fiber (absolute), and cholesterol (daily absolute; in mg/d) in the lower-fat diet. Estimates from the diet records better agreed with actual intakes than did estimates from the food-frequency questionnaire except for monounsaturated fat (absolute and percentage) in the high-fat diet and polyunsaturated fat (percentage) in the lower-fat diet and the very-low-fat diet.
Our data indicated that the food-frequency questionnaire did not provide reliable estimates of absolute amounts of dietary fats or cholesterol.
We have investigated the potential of asymmetric current injection for polarization switching in GaAs-based intracavity contacted vertical-cavity surface-emitting lasers using two sets of p- and ...n-type contacts per device. When using the contacts aligned along the 11~0 crystal direction, the observed laser polarization is parallel to 110, whereas, using the contacts along the 110 crystal direction, the polarization of the laser emission switches to a direction making an angle of 25/spl deg/-90/spl deg/ towards 110. To overcome this peculiar result, a careful design of the contact layers in the intracavity structure is required.
Abstract
Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation program under the ERA-NET ...co-fund action No. 680969 with ANR (ERA-CVD SICVALVES) and Agence Nationale de la Recherche
Background
Extracellular volume (ECV) determined by magnetic resonance imaging (MRI) is considered a marker of myocardial fibrosis and a predictor of mortality. In addition to diffuse fibrosis, aortic stenosis (AS) patients present increased ECV. However, the impact of regional ECV differences on ventricular conduction in AS patients has not been assessed.
Purpose
To investigate regional ECV differences in AS patients and to determine their impact on ventricular conduction.
Methods
MRI was performed in 22 AS patients (11 males, 11 females) before and 3 months after aortic valve replacement (AVR). Regional differences in ECV were determined between mid-ventricular and basal planes. To investigate the impact of these differences on conduction, a computational model of ventricular tissue (9x1x1 cm) was developed with human fiber orientation and transmural/apicobasal electrophysiology. The model was divided in two regions (Fig 1A), each representing tissue with different ECV. Extracellular conductivities (GE) in each region were adjusted to the patient with the highest difference in ECV between the planes (male 75y, post-AVR, ECV mid 25.5%, ECV base 31.3%) so that GE was 26.4% less for ECV of 31.3% compared to 25.5%. A model with uniform ECV of 25.5% was used as a control. The models were paced from the apical face with a S1-S2 protocol (S1: 750 ms, n=10, S2: 700-350 ms, n=1). To compare the results to conduction slowing from diffuse myocardial fibrosis, the simulations were repeated with an additional GE reduction by 40% in both regions to mimic conduction delays observed in fibrotic hearts. Ventricular conduction was compared between the models by analyzing conduction velocity (CV) measured between two points at the endocardium (Fig 1A, blue dots) and the occurrence of abnormalities in the form of non-uniform conduction, and/or conduction block after S2 (Fig 1B).
Results
Significantly higher ECV was found in the basal plane of AS patients when compared to the mid-ventricular plane before and after AVR (Fig 2), with the largest ECV found after AVR (mid-ventricular: p=0.0021; basal: p=0.0048). No sex-specific differences were found. The model representing the patient with the largest regional ECV difference showed slightly lower CV than the model with uniform ECV (92.9 vs. 96.0 cm/s, S2=500 ms). By contrast, myocardial fibrosis had a larger impact on CV slowing (92.9 vs. 79.2 cm/s, S2=500 ms, patient model, Fig 1C). Conduction block and non-uniform conduction occurred at comparable cycle lengths for all models (Fig 1D).
Conclusion
Regional differences in ECV were found in the ventricles of AS patients, but computer simulations suggest that these differences have a minimal effect on ventricular conduction when compared to diffuse fibrosis. Although the results suggest a limited electrophysiological relevance, additional studies are necessary to investigate whether these ECV differences have a more significant impact on cardiac mechanics.
Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in ...88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p <0.0001). Percent increases in the PP state were not significantly different in cases versus controls. Following the fat-rich meal, LDL and HDL cholesterol decreased by 5% and 4% in controls, and by 7% and 6% in patients, with no significant difference in percent changes between groups. Fasting values correlated very highly with PP values for all parameters (all p <0.0001). Our data indicate that although patients with CHD have higher fasting and PP levels of triglycerides, RLP cholesterol, and RLP triglycerides than controls, the response (percent increase) to a fat-rich meal is comparable in both groups. Thus, a feeding challenge is not essential for assessment of these lipoproteins. Moreover, it is not necessary to obtain a fasting sample to assess direct LDL and HDL cholesterol.
CONTEXT Following percutaneous coronary intervention (PCI), short-term clopidogrel
therapy in addition to aspirin leads to greater protection from thrombotic
complications than aspirin alone. ...However, the optimal duration of combination
oral antiplatelet therapy is unknown. Also, although current clinical data
suggest a benefit for beginning therapy with a clopidogrel loading dose prior
to PCI, the practical application of this therapy has not been prospectively
studied. OBJECTIVES To evaluate the benefit of long-term (12-month) treatment with clopidogrel
after PCI and to determine the benefit of initiating clopidogrel with a preprocedure
loading dose, both in addition to aspirin therapy. DESIGN, SETTING, AND PARTICIPANTS The Clopidogrel for the Reduction of Events During Observation (CREDO)
trial, a randomized, double-blind, placebo-controlled trial conducted among
2116 patients who were to undergo elective PCI or were deemed at high likelihood
of undergoing PCI, enrolled at 99 centers in North America from June 1999
through April 2001. INTERVENTIONS Patients were randomly assigned to receive a 300-mg clopidogrel loading
dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter,
all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through
12 months, patients in the loading-dose group received clopidogrel, 75 mg/d,
and those in the control group received placebo. Both groups received aspirin
throughout the study. MAIN OUTCOME MEASURES One-year incidence of the composite of death, myocardial infarction
(MI), or stroke in the intent-to-treat population; 28-day incidence of the
composite of death, MI, or urgent target vessel revascularization in the per-protocol
population. RESULTS At 1 year, long-term clopidogrel therapy was associated with a 26.9%
relative reduction in the combined risk of death, MI, or stroke (95% confidence
interval CI, 3.9%-44.4%; P = .02; absolute reduction,
3%). Clopidogrel pretreatment did not significantly reduce the combined risk
of death, MI, or urgent target vessel revascularization at 28 days (reduction,
18.5%; 95% CI, −14.2% to 41.8%; P = .23). However,
in a prespecified subgroup analysis, patients who received clopidogrel at
least 6 hours before PCI experienced a relative risk reduction of 38.6% (95%
CI, −1.6% to 62.9%; P = .051) for this end
point compared with no reduction with treatment less than 6 hours before PCI.
Risk of major bleeding at 1 year increased, but not significantly (8.8% with
clopidogrel vs 6.7% with placebo; P = .07). CONCLUSIONS Following PCI, long-term (1-year) clopidogrel therapy significantly
reduced the risk of adverse ischemic events. A loading dose of clopidogrel
given at least 3 hours before the procedure did not reduce events at 28 days,
but subgroup analyses suggest that longer intervals between the loading dose
and PCI may reduce events.
The recently cloned human GLUT9 gene, which maps to chromosome 4p15.3-p16, consists of 12 exons coding for a 540-amino acid protein. Based on a sequence entry (NCBI accession number BC018897) and ...screening of expressed sequence tags, we have cloned an alternative splice variant of GLUT9 from human kidney cDNA. The RNA of this splice variant consists of 13 exons and codes for a putative protein of 512 amino acids (GLUT9DeltaN). The predicted proteins differ only in their N terminus, suggesting a different subcellular localization and possible physiological role. Screening human tissue RNA by reverse transcription-PCR showed that GLUT9 is expressed mainly in kidney, liver, placenta, and leukocytes, whereas GLUT9DeltaN was detected only in kidney and placenta. The GLUT9 protein localized by immunohistochemistry to human kidney proximal tubules, and subcellular fractionation of human kidney revealed the GLUT9 protein in plasma membranes and high density microsomal membranes. Treatment of kidney membrane proteins with peptide N-glycosidase F showed that GLUT9 and GLUT9DeltaN are expressed in vivo. Localization of GLUT9 and GLUT9DeltaN in three kidney-derived cell lines revealed a plasma membrane distribution for GLUT9 in COS-7 and HEK293 cells, whereas GLUT9DeltaN showed a perinuclear pattern and plasma membrane staining in COS-7 and HEK293 cells, respectively. In polarized Madin-Darby canine kidney cells, GLUT9 trafficked to the basolateral membrane, whereas GLUT9DeltaN localized to the apical membrane. Using heterologous expression of GLUT9 in Xenopus oocytes, GLUT9 appears to be a functional isoform with low affinity for deoxyglucose. Deoxyglucose transport mediated by GLUT9 was not inhibited by cytochalasin B. GLUT9 did not bind cytochalasin B as shown by a cytochalasin B binding assay, indicating a similar behavior of GLUT9 compared with GLUT5.
Abstract
Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research has also received funding from the European Union’s Horizon 2020 ...research and innovation programme under the ERA-NET co-fund action No. 680969 (ERA-CVD SICVALVES) funded by the Austrian Science Fund (FWF), Grant I 4652-B to CMA.
This project has also received funding MedalCare 18HLT07 from the EMPIR programme co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation programme.
Background
Biophysics-based Cardiac Digital Twin (CDT) models strive to encode known physics and physiology in mathematical equations and tune these to represent individual patients. Owing to their mechanistic nature, when calibrated with high-fidelity CDTs show high potential to aide in clinical diagnostics, treatment planning, and prognostics. Challenges in building CDTs limit uptake and widespread in the clinics. Generation of CDT models and their personalisation based on measurable clinical data (i.e. the 12-lead electrocardiogram (ECG)) must be performed fast and automated, to be applicable at a clinical scale, and CDTs must replicate a patient’s electrophysiology (EP) with high fidelity to offer predictive capabilities for clinical use.
Purpose
We aimed to create the first personalized real-time in silico model of whole heart EP capable of both replicating the 12-lead ECG of a single subject under healthy sinus rhythm and subsequently capturing the complex mechanisms of various cardiac diseases.
Method
We constructed an automated pipeline for the generation of a ventricular-torso model personalised according to the 12-lead ECG during normal sinus rhythm (NSR), fitted with a physiologically-detailed cardiac conduction system facilitating retrograde activation, and included atrial and atrio-ventricular dynamics. Predictive capabilities of the mechanistic model were probed by interrupting conduction in the left and right bundle branches (LBBB, RBBB), by creating accessory paths, and by pacing at the right-ventricular (RV) apex. EP simulations were carried out with real-time performance. Goodness of fit was assessed for sinus rhythm in the 12 lead ECG. Computed pathological ECGs were evaluated with standard clinical diagnostic criteria.
Results
The computed 12-lead ECG of the personalised whole heart EP model under NSR showed close correspondence with the measured 12-lead ECG of the male subject. The 12 lead ECGs under the various pathologies manifested most morphological features in agreement with diagnostic criteria.
Conclusions
We report on a personalized real-time in silico model of whole heart EP for a single male subject that closely replicated the 12 lead ECG. Simulated pathological showed most known diagnostic features, but some features were less pronounced as not all factors of the underlying pathology were considered. The importance of dilation or slower cell-to-cell conduction in clinical LBBB aetiology, for example, was not considered. While the CDT shows promise for patient care in a single subject, broader validation with clinical and experimental data is needed to demonstrate agreement between models and physical reality. The pipeline must also be applied to additional subjects of both sexes.
Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic ...acid (TA), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. It also increased insulin-stimulated glucose disposal in patients with NIDDM after acute administration. This pilot study was initiated to see whether this compound also augments glucose disposal in humans after repeated treatment. Twenty patients with NIDDM received TA (500 mg/ 500 ml NaCl, 0.9%) as daily infusions over a period of ten days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11. Parenteral administration of TA resulted in a significant increase of insulin-stimulated glucose-disposal by about 30% (metabolic clearance rate for glucose, 2.5 +/- 0.3 vs. 3.2 +/- 0.4 ml/kg/min and insulin-sensitivity-index: 3.5 +/- 0.5 vs. 4.7 +/- 0.4 mg/kg/microU/ml; p < 0.05, Wilcoxon-Rank-Sum-Test). There were no changes in fasting plasma levels for glucose or insulin; this can be explained, however, by the short period of treatment and observation. This is the first clinical study to show that a ten day administration of TA is able to improve resistance of insulin-stimulated glucose disposal in NIDDM. Experimental data suggest several mechanisms in the mode of action. As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound.
In this study we introduce a
consisting of air quality models operating at both the global and regional scale. The work is motivated by the fact that these different types of models treat specific ...portions of the atmospheric spectrum with different levels of detail, and it is hypothesized that their combination can generate an ensemble that performs better than mono-scale ensembles. A detailed analysis of the hybrid ensemble is carried out in the attempt to investigate this hypothesis and determine the real benefit it produces compared to ensembles constructed from only global-scale or only regional-scale models. The study utilizes 13 regional and 7 global models participating in the Hemispheric Transport of Air Pollutants phase 2 (HTAP2)-Air Quality Model Evaluation International Initiative phase 3 (AQMEII3) activity and focuses on surface ozone concentrations over Europe for the year 2010. Observations from 405 monitoring rural stations are used for the evaluation of the ensemble performance. The analysis first compares the modelled and measured power spectra of all models and then assesses the properties of the mono-scale ensembles, particularly their level of redundancy, in order to inform the process of constructing the hybrid ensemble. This study has been conducted in the attempt to identify that the improvements obtained by the hybrid ensemble relative to the mono-scale ensembles can be attributed to its hybrid nature. The improvements are visible in a slight increase of the diversity (4 % for the hourly time series, 10 % for the daily maximum time series) and a smaller improvement of the accuracy compared to diversity. Root mean square error (RMSE) improved by 13-16 % compared to G and by 2-3 % compared to R. Probability of detection (POD) and false-alarm rate (FAR) show a remarkable improvement, with a steep increase in the largest POD values and smallest values of FAR across the concentration ranges. The results show that the optimal set is constructed from an equal number of global and regional models at only 15 % of the stations. This implies that for the majority of the cases the regional-scale set of models governs the ensemble. However given the high degree of redundancy that characterizes the regional-scale models, no further improvement could be expected in the ensemble performance by adding yet more regional models to it. Therefore the improvement obtained with the hybrid set can confidently be attributed to the different nature of the global models. The study strongly reaffirms the importance of an in-depth inspection of any ensemble of opportunity in order to extract the maximum amount of information and to have full control over the data used in the construction of the ensemble.
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