The influence of static portal pressure on liver biophysical properties.

The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH2O). Our experiments demonstrated that, with increasing portal pressure, rat livers showed higher water content, water diffusivity, and increased vessel sizes quantified by the vessel tissue volume fraction (VTVF). These effects were most pronounced in native, unconfined livers (VTVF: 300±120%, p<0.05, ADC: 88±29%, p<0.01), while still significant under confinement (confined: VTVF: 53±32%, p<0.01, ADC: 28±19%, p<0.05; confined-fixed: VTVF: 52±20%, p<0.001, ADC: 11±2%, p<0.01; confined-viscous: VTVF: 210±110%, p<0.01, ADC: 26±9%, p<0.001). Softening with elevated portal pressure (-12±5, p<0.05) occurred regardless of confinement and fixation. However, the liver stiffened when exposed to a more viscous inflow fluid (11±4%, p<0.001). Taken together, our results elucidate the complex relationship between macroscopic-biophysical parameters of liver tissue measured by mpMRI and vascular-fluid properties. Influenced by portal pressure, vascular permeability, and matrix crosslinking, liver stiffness is sensitive to intrinsic poroelastic properties, which, alongside vascular architecture and water diffusivity, may aid in the differential diagnosis of liver disease. STATEMENT OF SIGNIFICANCE: Using highly controllable ex vivo rat liver phantoms, hepatic biophysical properties such as tissue-vascular structure, stiffness, and water diffusivity were investigated using multiparametric MRI including multifrequency magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). Through elaborate tuning of the experimental conditions such as the static portal pressure, flow viscosity, amount and distribution of fluid content in the liver, we identified the contributions of the fluid component to the overall imaging-based biophysical properties of the liver. Our finding demonstrated the sensitivity of liver stiffness to the hepatic poroelastic properties, which may aid in the differential diagnosis of liver diseases.

Microscopic multifrequency MR elastography for mapping viscoelasticity in zebrafish.

PURPOSE: The zebrafish (Danio rerio) has become an important animal model in a wide range of biomedical research disciplines. Growing awareness of the role of biomechanical properties in tumor progression and neuronal development has led to an increasing interest in the noninvasive mapping of the viscoelastic properties of zebrafish by elastography methods applicable to bulky and nontranslucent tissues. METHODS: Microscopic multifrequency MR elastography is introduced for mapping shear wave speed (SWS) and loss angle (φ) as markers of stiffness and viscosity of muscle, brain, and neuroblastoma tumors in postmortem zebrafish with 60 µm in-plane resolution. Experiments were performed in a 7 Tesla MR scanner at 1, 1.2, and 1.4 kHz driving frequencies. RESULTS: Detailed zebrafish viscoelasticity maps revealed that the midbrain region (SWS = 3.1 ± 0.7 m/s, φ = 1.2 ± 0.3 radian [rad]) was stiffer and less viscous than telencephalon (SWS = 2.6 ± 0. 5 m/s, φ = 1.4 ± 0.2 rad) and optic tectum (SWS = 2.6 ± 0.5 m/s, φ = 1.3 ± 0.4 rad), whereas the cerebellum (SWS = 2.9 ± 0.6 m/s, φ = 0.9 ± 0.4 rad) was stiffer but less viscous than both (all p < .05). Overall, brain tissue (SWS = 2.9 ± 0.4 m/s, φ = 1.2 ± 0.2 rad) had similar stiffness but lower viscosity values than muscle tissue (SWS = 2.9 ± 0.5 m/s, φ = 1.4 ± 0.2 rad), whereas neuroblastoma (SWS = 2.4 ± 0.3 m/s, φ = 0.7 ± 0.1 rad, all p < .05) was the softest and least viscous tissue. CONCLUSION: Microscopic multifrequency MR elastography-generated maps of zebrafish show many details of viscoelasticity and resolve tissue regions, of great interest in neuromechanical and oncological research and for which our study provides first reference values.

Effect of Scalding Temperature on Growth of Staphylococcus aureus and Formation of Staphylococcal Enterotoxin during the Production of Alpine Cheese in a Laboratory Cheesemaking Model.

ABSTRACT: To reduce the number of cheese with potential Staphylococcus aureus contamination reaching consumers, European legislation has stipulated that all cheese must be tested for coagulase-positive staphylococci (CPS) at the point in production when numbers are expected to be highest. When CPS counts exceed 105 CFU/mL, staphylococcal enterotoxin (SE) tests must be conducted. When SE tests are positive, the cheese must be destroyed. Manufacturers of Swiss Alpine cheese are exempt from this legislation because SE formation in hard cheese is expected to be very unlikely because of the high scalding temperatures used for cheeses during production, which inactive CPS in the curd. However, this assumption has not been scientifically tested. A laboratory-scale cheese production experiment was performed in which the conditions corresponded to certain limitations in practical cheesemaking conditions such as temperature and time exposure as for production of Gruyere or Tete de Moine Swiss type cheeses. Raw milk aliquots (200 mL) were inoculated with five strains of CPS, and scalding temperatures of 46 to 56°C were used during cheese production. The temperatures applied after the curd was pressed were meant to reproduce the temperature curve in the peripheral zone of a real cheese wheel. Contrary to expectations, SE formation occurred and differed according to the scalding temperature (52 to 56°C). The differences in SE formation were more associated with strain type rather than temperature. These results indicate that the mechanisms of SE formation in cheese require further study.

Cheese yeasts.

Numerous traditionally aged cheeses are surface ripened and develop a biofilm, known as the cheese rind, on their surfaces. The rind of such cheeses comprises a complex community of bacterial and fungal species that are jointly responsible for the typical characteristics of the various cheese varieties. Surface ripening starts directly after brining with the rapid colonization of the cheese surface by yeasts. The initially dominant yeasts are acid and salt-tolerant and are capable of metabolizing the lactate produced by the starter lactic acid bacteria and of producing NH3 from amino acids. Both processes cause the pH of the cheese surface to rise dramatically. This so-called deacidification process enables the establishment of a salt-tolerant, Gram-positive bacterial community that is less acid-tolerant. Over the past decade, knowledge of yeast diversity in cheeses has increased considerably. The yeast species with the highest prevalence on surface-ripened cheeses are Debaryomyces hansenii and Geotrichum candidum, but up to 30 species can be found. In the cheese core, only lactose-fermenting yeasts, such as Kluyveromyces marxianus, are expected to grow. Yeasts are recognized as having an indispensable impact on the development of cheese flavour and texture because of their deacidifying, proteolytic, and/or lipolytic activity. Yeasts are used not only in the production of surface-ripened cheeses but also as adjunct cultures in the vat milk in order to modify ripening behaviour and flavour of the cheese. However, yeasts may also be responsible for spoilage of cheese, causing early blowing, off-flavour, brown discolouration, and other visible alterations of cheese.

Polymorphisms in the IGF1 signalling pathway including the myostatin gene are associated with left ventricular mass in male athletes.

BACKGROUND: Athlete's heart as an adaptation to long-time and intensive endurance training can vary considerably between individuals. Genetic polymorphisms in the cardiological relevant insulin-like growth factor 1 (IGF1) signalling pathway seem to have an essential influence on the extent of physiological hypertrophy. OBJECTIVE: Analysis of polymorphisms in the genes of IGF1, IGF1 receptor (IGF1R) and the negative regulator of the cardiac IGF1 signalling pathway, myostatin (MSTN), and their relation to left ventricular mass (LVM) of endurance athletes. METHODS: In 110 elite endurance athletes or athletes with a high amount of endurance training (75 males and 35 females) and 27 male controls, which were examined by echocardiographic imaging methods and ergometric exercise-testing, the genotypes of a cytosine-adenine repeat polymorphism in the promoter region of the IGF1 gene and a G/A substitution at position 3174 in the IGF1R gene were determined. Additionally, a mutation screen of the MSTN gene was performed. RESULTS: The polymorphisms in the IGF1 and the IGF1R gene showed a significant relation to the LVM for male (IGF1: p=0.003; IGF1R: p=0.01), but not for female athletes. The same applies to a previously unnoticed polymorphism in the 1 intron of the MSTN gene, whose deletion allele (AAA→AA) appears to increase the myostatic effect (p=0.015). Moreover, combinations of the polymorphisms showed significant synergistic effects on the LVM of the male athletes. CONCLUSIONS: The authors' results argue for the importance of polymorphisms in the IGF1 signalling pathway in combination with MSTN on the variant degree of physiological hypertrophy of male athletes.

Non-invasive ultrasonic cardiac output monitoring in exercise testing.

BACKGROUND: The purpose of this study was to evaluate the relationship of breath-by-breath oxygen uptake (VO(2)) and CO, cardiac index (CI), stroke volume (SV) and heart rate (HR) determined by a non-invasive continuous wave (CW) Doppler-based system (USCOM) in healthy adolescent and adult athletes during exercise treadmill testing. METHODS: Twenty athletes were enrolled for a standardized ramp treadmill test including transthoracic echocardiography at rest, incremental breath-by-breath spiroergometry, lactate kinetics and CW Doppler. RESULTS: VO(2) max was 51+/-11 ml/min/kg in the adolescent cross country skiers (CI 8.2+/-1.2 l/min/m(2)) and 50+/-12 ml/min/kg in adult soccer referees (CI 7.1+/-1.2 l/min/m(2)). CW Doppler hemodynamic variables showed significant correlation with VO(2) (p<0.01, n=95) across the total of measures, with excellent correlation demonstrated for CO and CI (0.904 and 0.897), while HR and SV showed good to very good correlation with r values of 0.842 and 0.766, respectively. Correlation of the variables at peak exercise and 1 and 3 min after recovery, demonstrate that CO and SV show superior correlation with peak oxygen consumption (VO(2) max). The regression equation for VO(2) and CO(USCOM) was VO(2)=4.43CO(USCOM)-10.3. CONCLUSION: CW Doppler measurement of cardiac output is feasible as a measure of cardiac performance during standardized treadmill testing in adolescent and adult athletes.