Human Bifidobacterium strains as adjunct cultures in Spanish sheep milk cheese.

Three bifidobacteria strains of human origin (Bifidobacterium pseudolongum INIA P2, Bifidobacterium breve INIA P734, and Bifidobacterium longum INIA P678) were used as potential probiotic adjunct cultures for the manufacture of pasteurized sheep milk cheese. Bifidobacteria were inoculated at 5 to 6 log cfu/mL in milk vats. Microbiological, physicochemical, rheological, color, and sensory characteristics were determined at 7, 28, and 60 d of ripening. Counts of B. pseudolongum INIA P2 remained above 6 log cfu/g during 60 d of ripening as well as after further simulated gastrointestinal digestion of cheeses. Bifidobacterium breve INIA P734 counts remained stable during 28 d and decreased by less than 1 log unit after simulated digestion. Bifidobacterium longum INIA P678 counts dropped sharply during cheese manufacture and ripening and were below detection level after simulated digestion. Addition of bifidobacteria strains did not affect starter viability, cheese pH, dry matter, water activity, or salt content but significantly increased overall proteolysis and the concentration of some free amino acids. Cheeses with bifidobacteria exhibited no significant differences in most sensory characteristics with respect to control cheese. According to our results, B. breve INIA P734 and B. pseudolongum INIA P2 are promising candidates as probiotic adjunct cultures in fresh and semi-hard sheep milk cheese.

Contribution of autochthonous lactic acid bacteria to the typical flavour of raw goat milk cheeses.

In this study, a collection of 298 wild strains of lactic acid bacteria (LAB) isolated from raw goat milk cheeses, belonging to 8 genera and 24 species, was investigated for their ability to generate volatile compounds. Sensory evaluation showed that goat milk cultures of Leuconostoc and Lactococcus strains reached the highest scores for dairy odour attributes. Fifty six LAB strains with the highest sensory evaluation scores (one per each ten, or fraction, of those belonging to the same species) were selected for gas chromatography-mass spectrometry (GC-MS) analysis. A total of 34 volatile compounds (five carboxylic acids, eleven alcohols, six aldehydes, six ketones, one ester, and five miscellaneous compounds) were detected in lactic curds made with each one of 56 selected LAB strains. The number of volatile compounds in individual curds varied from 15 to 33 while the total abundance of volatile compounds in individual curds ranged from 1.98- to 17.50-fold the total abundance in uninoculated curd. Major differences in volatile generation were related to amino acid catabolism.

Volatile compounds, odor, and aroma of La Serena cheese high-pressure treated at two different stages of ripening.

La Serena cheeses made from raw Merino ewe's milk were high-pressure (HP) treated at 300 or 400 MPa for 10 min on d 2 or 50 after manufacture. Ripening of HP-treated and control cheeses proceeded until d 60 at 8 degrees C. Volatile compounds were determined throughout ripening, and analysis of related sensory characteristics was carried out on ripe cheeses. High-pressure treatments on d 2 enhanced the formation of branched-chain aldehydes and of 2-alcohols except 2-butanol, but retarded that of n-aldehydes, 2-methyl ketones, dihydroxy-ketones, n-alcohols, unsaturated alcohols, ethyl esters, propyl esters, and branched-chain esters. Differences between HP-treated and control cheeses in the levels of some volatile compounds tended to disappear during ripening. The odor of ripe cheeses was scarcely affected by HP treatments on d 2, but aroma quality and intensity scores were lowered in comparison with control cheese of the same age. On the other hand, HP treatments on d 50 did not influence either the volatile compound profile or the sensory characteristics of 60-d-old cheese.

Effect of high-pressure treatment and a bacteriocin-producing lactic culture on the proteolysis, texture, and taste of Hispánico cheese.

The effects of high-pressure treatment, by itself or in combination with a bacteriocin-producing culture added to milk, on the proteolysis, texture, and taste of Hispánico cheese were investigated. Two vats of cheese were manufactured from a mixture of cow and ewe milk. Milk in one vat was inoculated with 0.5% Lactococcus lactis ssp. lactis INIA 415, a nisin Z and lacticin 481 producer; 0.5% L. lactis ssp. lactis INIA 415-2, a bacteriocin-nonproducing mutant; and 2% of a commercial Streptococcus thermophilus culture. Milk in the other vat was inoculated with 1% L. lactis ssp. lactis INIA 415-2 and 2% S. thermophilus culture. After ripening for 15 d at 12 degrees C, half of the cheeses from each vat were treated at 400 MPa for 5 min at 10 degrees C. Ripening of high-pressure-treated and untreated cheeses continued at 12 degrees C until d 50. High-pressure treatment of cheese made from milk without the bacteriocin producer accelerated casein degradation and increased the free AA content, but it did not significantly influence the taste quality or taste intensity of the cheese. Addition of the bacteriocin producer to milk lowered the ratio of hydrophobic peptides to hydrophilic peptides, increased the free AA content, and enhanced the taste intensity. The combination of milk inoculation with the bacteriocin producer and high-pressure treatment of the cheese resulted in higher levels of both hydrophobic and hydrophilic peptides but had no significant effect on the free AA content, taste quality, or taste intensity.

Proteolysis of Hispanico cheese manufactured using lacticin 481-producing Lactococcus lactis ssp. lactis INIA 639.

Hispánico cheese was manufactured using lacticin 481-producing Lactococcus lactis ssp. lactis INIA 639, bacteriocin-nonproducing L. lactis ssp. lactis INIA 437, or a combination of both strains, as starter cultures. Lactobacillus helveticus LH 92, a culture of high amino-peptidase activity sensitive to lacticin 481, was added to all vats. Milk inoculation with the bacteriocin producer promoted early lysis of Lb. helveticus cells in cheese. Cell-free aminopeptidase activity in cheese made with the 3 lactic cultures was 1.8 times the level reached in cheese made only with L. lactis strain INIA 437 and Lb. helveticus, after 15 d of ripening. Proteolysis (as estimated by the o-phthaldialdehyde method) in cheese made with the 3 lactic cultures was twice as high, and the level of total free amino acids 2.4 times the level found in cheese made only with L. lactis strain INIA 437 and Lb. helveticus, after 25 d of ripening. Hydrophobic and hydrophilic peptides and their ratio were at the lowest levels in cheese made with the 3 lactic cultures, which received the lowest scores for bitterness and the highest scores for taste quality.

Short communication: Inactivation of microbial contaminants in raw milk La Serena cheese by high-pressure treatments.

La Serena cheese, a Spanish variety made from Merino ewes' raw milk, has a high pH value, low salt content, and high moisture, conditions that are all favorable for growth and survival of contaminating microorganisms, including pathogens. To improve its microbiological quality and safety, high-pressure treatments at 300 or 400 MPa for 10 min at 10 degrees C were applied to 2 batches of La Serena cheese on d 2 or 50 of ripening. Cheese treated on d 2 at 300 MPa showed viable aerobic counts that were 0.99 log units lower than those for control cheese on d 3 and showed counts of enterococci, coagulase-positive staphylococci, gram-negative bacteria, and coliforms that were 2.05, 0.49, 3.14, and 4.13 log units lower, respectively, than control cheese. For cheese treated on d 2 at 400 MPa, the respective reductions in counts were 2.02, 2.68, 1.45, 3.96, and 5.50 log units. On d 60, viable aerobic counts in cheese treated on d 50 at 300 MPa were 0.50 log units lower than those in control cheese, and counts of enterococci, gram-negative bacteria, and coliforms were 1.37, 2.30, and 4.85 log units lower, respectively. For cheese treated on d 50 at 400 MPa, the respective reductions in counts were 1.29, 1.98, 4.47, and > 5 log units. High-pressure treatments at 300 or 400 MPa on d 2 or 50 reduced significantly the counts of undesirable microorganisms, improving the microbiological quality and safety of La Serena cheese immediately after treatment and at the end of the ripening period.

CSI-ISC--Concepts for smooth integration of health care information system components into established processes of patient care.

OBJECTIVES: The introduction of information system components (ISCs) usually leads to a change in existing processes, e.g. processes of patient care. These processes might become even more complex and variable than before. An early participation of end users and a better understanding of human factors during design and introduction of ISCs are key factors for a successful introduction of ISCs in health care. Nonetheless no specialized methods have been developed until now to systematically support the integration of ISCs in existing processes of patient care while taking into account these requirements. In this paper, therefore, we introduce a procedure model to implement Concepts for Smooth Integration of ISCs (CSI-ISC). METHODS: Established theories from economics and social sciences have been applied in our model, among them the stress-strain-concept, the contrastive task analysis (KABA), and the phase model for the management of information systems. RESULTS: CSI-ISC is based on the fact that while introducing new information system components, users experience additional workload. One essential aim during the introduction process therefore should be to systematically identify, prioritize and ameliorate workloads that are being imposed on human beings by information technology in health care. To support this, CSI-ISC consists of a static part (workload framework) and a dynamic part (guideline for the introduction of information system components into existing processes of patient care). CONCLUSIONS: The application of CSI-ISC offers the potential to minimize additional workload caused by information system components systematically. CSI-ISC rationalizes decisions and supports the integration of the information system component into existing processes of patient care.

TERMTrial--terminology-based documentation systems for cooperative clinical trials.

Within cooperative groups of multi-center clinical trials a standardized documentation is a prerequisite for communication and sharing of data. Standardizing documentation systems means standardizing the underlying terminology. The management and consistent application of terminology systems is a difficult and fault-prone task, which should be supported by appropriate software tools. Today, documentation systems for clinical trials are often implemented as so-called Remote-Data-Entry-Systems (RDE-systems). Although there are many commercial systems, which support the development of RDE-systems there is none offering a comprehensive terminological support. Therefore, we developed the software system TERMTrial which consists of a component for the definition and management of terminology systems for cooperative groups of clinical trials and two components for the terminology-based automatic generation of trial databases and terminology-based interactive design of electronic case report forms (eCRFs). TERMTrial combines the advantages of remote data entry with a comprehensive terminological control.

Towards clinical bioinformatics: advancing genomic medicine with informatics methods and tools.

OBJECTIVES: To summarize the challenges facing clinical applications in the light of growing research results in genomic medicine and bioinformatics. METHODS: Analysis of the contents of the Yearbook of Medical Informatics 2004 of the International Medical Informatics Association (IMIA). RESULTS: The Yearbook of Medical Informatics 2004 includes 32 articles selected from 22 peer-reviewed scientific journals. A special section on clinical bioinformatics highlights recent developments in this field. Several guest editors review the promises and limitations of available methods and resources from biomedical informatics that are relevant to clinical medicine. Integrated data and knowledge resources are generally regarded to be central and key issues for clinical bioinformatics. Further review papers deal with public health implications of bioinformatics, knowledge management and trends in health care education. The Yearbook includes for the first time a section on the history of medical informatics, where the significant impact of the Reisensburg protocol 1973 on international health and medical informatics education is examined. CONCLUSIONS: Close collaboration between bioinformatics and medical informatics researchers can contribute to new insights in genomic medicine and contribute towards the more efficient and effective use of genomic data to advance clinical care.

A meta-model of chemotherapy planning in the multi-hospital/multi-trial-center-environment of pediatric oncology.

OBJECTIVE: Chemotherapy planning in pediatric oncology is complex and time-consuming. The correctness of the calculation according to state-of-the-art research is crucial for curing the child. Computer-assistance can be of great value. The objective of our research was to work out a meta-model of chemotherapy planning based on the Unified Modeling Language (UML). The meta-model is used for the development of an application system which serves as a knowledge-acquisition tool for chemotherapy protocols in pediatric oncology as well as for providing protocol-based care. METHODS: We applied evolutionary prototyping, software reengineering techniques and grounded theory, a qualitative method in social research. We repeated the following steps several times over the years: Based on a requirements analysis (i) a meta-model was developed or adapted, respectively (ii). The meta-model served as a basis for implementing evolutionary prototypes (iii). Further requirements were identified (i) from clinical use of the systems. RESULTS: We developed a comprehensive UML-based meta-model for chemotherapy planning in pediatric oncology (chemoMM). We implemented it and introduced evolutionary prototypes (CATIPO and DOSPO) in several medical centers. Systematic validation of the prototypes enabled us to derive a final meta-model which covers the requirements that have turned out to be necessary in clinical routine. CONCLUSIONS: We have developed an application system that fits well into clinical routine of pediatric oncology in Germany. Validation results have shown that the implementation of the meta-model chemoMM can adequately support the knowledge acquisition process for protocol-based care.

Proteolysis, volatile compounds, and sensory evaluation in Hispánico cheese manufactured with the addition of a thermophilic adjunct culture, nisin, and calcium alginate-nisin microparticles.

Nisin, free or incorporated in calcium alginate microparticles, was added to pasteurized milk (80% cows' and 20% ewes' milk) used for the manufacture of Hispánico cheese with a mesophilic starter and a thermophilic adjunct culture of high aminopeptidase activity. Addition of nisin incorporated in microparticles promoted early lysis of thermophilic adjunct culture bacteria. Extracellular aminopeptidase activity in 1-d-old cheese made with both thermophilic adjunct culture and nisin incorporated in microparticles was 1.8-fold higher than in cheese made with thermophilic adjunct culture and free nisin and 2.0-fold higher than in cheese made only with thermophilic adjunct culture without any addition of nisin. Addition of nisin, free or incorporated in microparticles, did not influence cheese proteolysis measured using hydrophilic or hydrophobic peptides, o-phthaldialdehyde ripening index, or free amino acids. Moreover, a total of 37 volatile compounds were identified in the volatile fraction of Hispánico cheese, using a dynamic headspace technique with a purge and trap system followed by a gas chromatography mass spectrometry analysis. The volatile compound profile was not influenced by nisin addition, either free or incorporated in microparticles, but addition of thermophilic adjunct culture enhanced the formation of 2-butanone, diacetyl, 2,3-pentanedione and acetoin and improved the flavor quality (sensory panel) of cheese.

Medical informatics and the quality of health: new approaches to support patient care - findings from the IMIA Yearbook of Medical Informatics 2003.

OBJECTIVES: The Yearbook of Medical Informatics is published annually by the International Medical Informatics Association (IMIA) and contains a selection of excellent papers on medical informatics research which have been recently published (http://www. yearbook.uni-hd.de). The 2003 Yearbook of Medical Informatics took as its theme the role of medical informatics for the quality of health care. In this paper, we will discuss challenges for health care, and the lessons learned from editing IMIA Yearbook 2003. RESULTS AND CONCLUSIONS: Modern information processing methodology and information and communication technology have strongly influenced our societies and health care. As a consequence of this, medical informatics as a discipline has taken a leading role in the further development of health care. This involves developing information systems that enhance opportunities for global access to health services and medical knowledge. Informatics methodology and technology will facilitate high quality of care in aging societies, and will decrease the possibilities of health care errors. It will also enable the dissemination of the latest medical and health information on the web to consumers and health care providers alike. The selected papers of the IMIA Yearbook 2003 present clear examples and future challenges, and they highlight how various sub-disciplines of medical informatics can contribute to this.

Hospital sostenible: plan de acción ambiental / Sustainable hospital: environmental action plan

Aunque alcanzar la filosofía del hospital sostenible desde el punto de vista de su respeto por el medio ambiente puede considerarse un gran valor, si bien todavía poco desarrollado en el ámbito sanitario, no cabe duda de que cada vez, con mayor frecuencia, ésta va a ser una preocupación que va a conllevar la realización de acciones solidarias desde el punto de vista ecológico. Este trabajo presenta un plan de acción ambiental para un hospital, que tiene como objetivo general encauzar las actividades del hospital hacia un modelo de sostenibilidad global, en la que las afecciones al medio ambiente se vean minimizadas y como objetivos específicos conocer sus problemas ambientales, asegurar la calidad ambiental, prevenir riesgos, etc. Se presenta el plan de acción ambiental elaborado, así como los resultados obtenidos en el primer año de aplicación (AU)

Molecular dynamics simulations of pressure effects on hydrophobic interactions.

We report results on the pressure effects on hydrophobic interactions obtained from molecular dynamics simulations of aqueous solutions of methanes in water. A wide range of pressures that is relevant to pressure denaturation of proteins is investigated. The characteristic features of water-mediated interactions between hydrophobic solutes are found to be pressure-dependent. In particular, with increasing pressure we find that (1) the solvent-separated configurations in the solute-solute potential of mean force (PMF) are stabilized with respect to the contact configurations; (2) the desolvation barrier increases monotonically with respect to both contact and solvent-separated configurations; (3) the locations of the minima and the barrier move toward shorter separations; and (4) pressure effects are considerably amplified for larger hydrophobic solutes. Together, these observations lend strong support to the picture of the pressure denaturation process proposed previously by Hummer et al. (Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1552): with increasing pressure, the transfer of water into protein interior becomes key to the pressure denaturation process, leading to the dissociation of close hydrophobic contacts and subsequent swelling of the hydrophobic protein interior through insertions of water molecules. The pressure dependence of the PMF between larger hydrophobic solutes shows that pressure effects on the interaction between hydrophobic amino acids may be considerably amplified compared to those on the methane-methane PMF.

Nonlinear dynamics of heart rate variability in cocaine-exposed neonates during sleep.

The aim of this study was to determine the effects of prenatal cocaine exposure (PCE) on the dynamics of heart rate variability in full-term neonates during sleep. R-R interval (RRI) time series from 9 infants with PCE and 12 controls during periods of stable quiet sleep and active sleep were analyzed using autoregressive modeling and nonlinear dynamics. There were no differences between the two groups in spectral power distribution, approximate entropy, correlation dimension, and nonlinear predictability. However, application of surrogate data analysis to these measures revealed a significant degree of nonlinear RRI dynamics in all subjects. A parametric model, consisting of a nonlinear delayed-feedback system with stochastic noise as the perturbing input, was employed to estimate the relative contributions of linear and nonlinear deterministic dynamics in the data. Both infant groups showed similar proportional contributions in linear, nonlinear, and stochastic dynamics. However, approximate entropy, correlation dimension, and nonlinear prediction error were all decreased in active versus quiet sleep; in addition, the parametric model revealed a doubling of the linear component and a halving of the nonlinear contribution to overall heart rate variability. Spectral analysis indicated a shift in relative power toward lower frequencies. We conclude that 1) RRI dynamics in infants with PCE and normal controls are similar; and 2) in both groups, sympathetic dominance during active sleep produces primarily periodic low-frequency oscillations in RRI, whereas in quiet sleep vagal modulation leads to RRI fluctuations that are broadband and dynamically more complex.

Proteolysis and formation of volatile compounds in cheese manufactured with a bacteriocin-producing adjunct culture.

Hispánico cheese, a semi-hard Spanish variety, was manufactured from a mixture of pasteurized cows' and ewes' milks (4:1) using a commercial mesophilic LD-type starter comprising Lactococcus lactis subsp. cremoris, Lc. lactis subsp. lactis, Lc. lactis subsp. lactis var diacetylactis and Leuconostoc mesenteroides subsp. cremoris. Varying amounts (0-1.0 g/kg) of an Enterococcus faecalis INIA 4 culture in milk were added as a bacteriocin-producing adjunct. Differences in pH between cheeses manufactured with and without the bacteriocin producer did not exceed 0.11 pH units. Starter lactococci lost viability more rapidly in cheeses made with the bacteriocin producer, which reached counts of up to 6 x 10(7) cfu/g during ripening. Aminopeptidase activity in 1-d-old cheese made from milk inoculated with 1.0 g bacteriocin-producing culture/kg was twice that in control cheese. Degrees of overall proteolysis and levels of total free amino acids in 45-d-old cheese made with 1.0 g bacteriocin-producing culture/kg were 1.80-fold and 2.17-fold those in control cheese of the same age. Inoculating milk with 1.0 g/kg bacteriocin-producing culture reduced the level of hydrophobic peptides in the resultant cheese, increased the concentrations of 3-methyl-1-butanal, diacetyl and acetoin, and resulted in the highest scores for flavour quality and flavour intensity throughout ripening.

The effects of cultivating lactic starter cultures with bacteriocin-producing lactic acid bacteria.

The effects of bacteriocins produced by six strains of lactic acid bacteria on 9 mesophilic and 11 thermophilic commercial starter cultures were investigated in mixed cultures of commercial starters with bacteriocin-producing strains in milk. The bacteriocins produced by the test organisms were nisin A, nisin Z, lacticin 481, enterocin AS-48, a novel enterocin, and a novel plantaricin. Mesophilic commercial starters were in most cases tolerant of bacteriocins, with only two of the starters being partially inhibited, one by four and the other by two bacteriocins. The aminopeptidase activities of mesophilic starters were generally low, and only one of the combinations of mesophilic starter-bacteriocin producer gave double the aminopeptidase activity of the starter culture without the bacteriocin producer. Thermophilic commercial starters were more sensitive to bacteriocins than mesophilic starters, with six thermophilic starters being partially inhibited by at least one of the bacteriocins. Their aminopeptidase activities were generally higher than those of the mesophilic starters. The aminopeptidase activities of seven thermophilic starters were increased in the presence of bacteriocins, by factors of up to 9.0 as compared with the corresponding starter cultures alone. Bacteriocin-producing strains may be used as adjunct cultures to mesophilic starters for the inhibition of pathogens in soft and semihard cheeses, because mesophilic starters are rather tolerant of bacteriocins. Bacteriocin producers may also be used as adjunct cultures to thermophilic starters of high aminopeptidase activity, more sensitive to lysis by bacteriocins than mesophilic starters, for the acceleration of ripening in semihard and hard cheeses.

Helix nucleation kinetics from molecular simulations in explicit solvent.

We study the reversible folding/unfolding of short Ala and Gly-based peptides by molecular dynamics simulations of all-atom models in explicit water solvent. A kinetic analysis shows that the formation of a first alpha-helical turn occurs within 0.1-1 ns, in agreement with the analyses of laser temperature jump experiments. The unfolding times exhibit Arrhenius temperature dependence. For a rapidly nucleating all-Ala peptide, the helix nucleation time depends only weakly on temperature. For a peptide with enthalpically competing turn-like structures, helix nucleation exhibits an Arrhenius temperature dependence, corresponding to the unfolding of enthalpic traps in the coil ensemble. An analysis of structures in a "transition-state ensemble" shows that helix-to-coil transitions occur predominantly through breaking of hydrogen bonds at the helix ends, particularly at the C-terminus. The temperature dependence of the transition-state ensemble and the corresponding folding/unfolding pathways illustrate that folding mechanisms can change with temperature, possibly complicating the interpretation of high-temperature unfolding simulations. The timescale of helix formation is an essential factor in molecular models of protein folding. The rapid helix nucleation observed here suggests that transient helices form early in the folding event.

Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis.

Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved.

Conformational diffusion and helix formation kinetics.

The time, temperature, and sequence dependences of helix formation kinetics of fully atomistic peptide models in explicit solvent are described quantitatively by a diffusive search within the coil state with barrierless transitions into the helical state. Conformational diffusion leads to nonexponential kinetics and jump-width dependences in temperature jump experiments.