Real-life cost-effectiveness of benralizumab in patients with severe asthma.

BACKGROUND: Availability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma. METHODS: This was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs). RESULTS: After 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score. CONCLUSIONS: All the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.

Electronic Raman Scattering in Twistronic Few-Layer Graphene.

We study electronic contribution to the Raman scattering signals of two-, three- and four-layer graphene with layers at one of the interfaces twisted by a small angle with respect to each other. We find that the Raman spectra of these systems feature two peaks produced by van Hove singularities in moiré minibands of twistronic graphene, one related to direct hybridization of the Dirac states, and the other resulting from band folding caused by moiré superlattice. The positions of both peaks strongly depend on the twist angle, so that their detection can be used for noninvasive characterization of the twist, even in hBN-encapsulated structures.

Effect of calving age on genetic evaluation of milk yield in Holstein cattle.

The aim of this study was to evaluate the effect of including calving age (CA) on genetic evaluation models for Holstein cattle. The evaluated models included the permanent environment, the sire-herd interactions, and the animals and residual effects as random. The fixed effects included the average production of milk, fat, and protein and the herd-year-season effect. The analyzed data included 603,521 records of milk production (in kg) corresponding to 438,098 animals from 527 herds. Additionally, there were 179,122 records of fat and protein components, corresponding to 148,930 animals from 137 herds. The records were classified by first lactation only (FL) and all available lactations (AL) for validation test (VT). The FL records corresponded to 275,487 milk production records with a mean of 10,874.1 ± 2773.9 kg at a mean CA of 25.6 ± 4.2 months. For FL, the milk components consisted of 78,955 records with a mean fat production of 392.86 ± 89.9 kg, a mean protein production of 362.8 ± 74.9 kg and a mean CA of 25.2 ± 4.1 months. For AL, the number of records was 603,521 for milk production with a mean of 10,802.8 ± 2905.9 kg and a mean CA of 35.6 ± 11.5 months. For the milk components, there were 179,122 records with a mean of 36.1 ± 9.5 months for CA and 388.3 ± 98.4 kg and 356.7 ± 82.6 kg for fat and protein, respectively. Three models were compared: the base model (M0) described above, and two alternative models that included CA in a linear and quadratic form (M1 and M2, respectively). Estimations of the variance components (VC) and breeding value (BV) were obtained using a repeatability animal model, with the same phenotypic and pedigree information used for all models. To select the best fit model for the data, a likelihood ratio test (LRtest) was used. A validation test (VT) was also applied to each model to evaluate the consistency of the genetic trends for females with information on AL and FL. The inclusion of CA in its linear form (M1) was the model that achieved the best results in the LRtest and an acceptable value for the VT. These results show that CA improves the model fit for BV prediction and reliability.

Distributed detection of hydrogen and deuterium diffusion into a single-mode optical fiber with chirped-pulse phase-sensitive optical time-domain reflectometry.

For some infrastructures such as oil and gas extraction boreholes or radioactive waste repositories, where distributed optical fiber sensors are employed to grant the safety of the facilities, the presence of gas species such as hydrogen or deuterium is one of the most relevant parameters to monitor. The possibility of employing the same kind of sensors for this purpose is of special interest, reducing the cost by employing a single interrogator, able to measure multiple parameters by simply employing adequate sensing fibers. To meet this goal, we present here a chemical sensor based on chirped-pulse phase-sensitive optical time-domain reflectometry (CP-φOTDR), which is able to detect these species while they diffuse into the silica fiber. The ability of chirped-pulse φOTDR to measure a change in refractive index with sensitivity around 10-8 has allowed determining hydrogen concentration with accuracy on the order of 10-3 mol/m3 and spatial resolution ∼6 m. Another experiment provides an indirect measurement of the solubility of deuterium in a standard telecom-grade optical fiber, which is found to be around 1.47×1024 m3/bar.

Pedigree verification and parentage assignment using genomic information in the Mexican Holstein population.

Genealogical information is an essential tool for carrying out any genetic improvement program. The objective of this study was to determine the accuracy of pedigree information in the Mexican registered Holstein population using genomic data available in Mexico and for the US Holstein population. The study included 7,508 animals (158 sires and 7,350 cows) that were born from 2002 through 2014, registered with Holstein de México, and genotyped with single nucleotide polymorphism arrays of different densities. Parentage could not be validated for 17% of sires of cows and 12% of sires of bulls. Most (79%) of the dams of cows and the dams of bulls had no genotype available and could not be validated. A parentage test was possible for only 6,104 sires of cows, 139 sires of bulls, 1,519 dams of cows, and 33 dams of bulls. Of the animals with a parentage test, parent assignment was confirmed for 89% of sires of cows, 92% of dams of cows, 95% of sires of bulls, and 97% of dams of bulls. Parent discovery was possible for some animals without confirmed parents: 17% for sires of cows, 2.5% for dams of cows, 43% for sires of bulls, and 0% for dams of bulls. Of the 7,795 progeny tests, 777 had parent conflicts, which is an error rate of 9.97% for parental recording in the population, a rate that is similar to those recently reported for other populations. True parents for some progeny conflicts (15%) were discovered for the Mexican population, and the remaining parents were assigned as unknown. Expected effects of misidentification on rate of genetic gain could be decreased by half if genealogical errors were decreased to 5%. This study indicates that genotyping and genealogy recovery may help in increasing rates of genetic improvement in the Mexican registered Holstein population.

Digestibility of Quinoa (Chenopodium quinoa Willd.) Protein Concentrate and Its Potential to Inhibit Lipid Peroxidation in the Zebrafish Larvae Model.

Quinoa protein concentrate (QPC) was extracted and digested under in vitro gastrointestinal conditions. The protein content of QPC was in the range between 52.40 and 65.01% depending on the assay used. Quinoa proteins were almost completely hydrolyzed by pepsin at pH of 1.2, 2.0, and 3.2. At high pH, only partial hydrolysis was observed. During the duodenal phase, no intact proteins were visible, indicating their susceptibility to the in vitro simulated digestive conditions. Zebrafish larvae model was used to evaluate the in vivo ability of gastrointestinal digests to inhibit lipid peroxidation. Gastric digestion at pH 1.2 showed the highest lipid peroxidation inhibition percentage (75.15%). The lipid peroxidation activity increased after the duodenal phase. The digest obtained at the end of the digestive process showed an inhibition percentage of 82.10%, comparable to that showed when using BHT as positive control (87.13%).

Single-shot distributed temperature and strain tracking using direct detection phase-sensitive OTDR with chirped pulses.

So far, the optical pulses used in phase-sensitive OTDR (ΦOTDR) were typically engineered so as to have a constant phase along the pulse. In this work, it is demonstrated that by acting on the phase profile of the optical pulses, it is possible to introduce important conceptual and practical changes to the traditional ΦOTDR operation, thus opening a door for new possibilities which are yet to be explored. Using a ΦOTDR with linearly chirped pulses and direct detection, the distributed measurement of temperature/strain changes from trace to trace, with 1mK/4nε resolution, is theoreticaly and experimentaly demonstrated. The measurand resolution and sensitivity can be tuned by acting on the pulse chirp profile. The technique does not require a frequency sweep, thus greatly decreasing the measurement time and complexity of the system, while maintaining the potential for metric spatial resolutions over tens of kilometers as in conventional ΦOTDR. The technique allows for measurements at kHz rates, while maintaining reliability over several hours.

Effect of reference population size and available ancestor genotypes on imputation of Mexican Holstein genotypes.

The effects of reference population size and the availability of information from genotyped ancestors on the accuracy of imputation of single nucleotide polymorphisms (SNP) were investigated for Mexican Holstein cattle. Three scenarios for reference population size were examined: (1) a local population of 2,011 genotyped Mexican Holsteins, (2) animals in scenario 1 plus 866 Holsteins in the US genotype database (GDB) with genotyped Mexican daughters, and (3) animals in scenario 1 and all US GDB Holsteins (338,073). Genotypes from 4 chip densities (2 low density, 1 mid density, and 1 high density) were imputed using findhap (version 3) to the 45,195 markers on the mid-density chip. Imputation success was determined by comparing the numbers of SNP with 1 or 2 alleles missing and the numbers of differently predicted SNP (conflicts) among the 3 scenarios. Imputation accuracy improved as chip density and numbers of genotyped ancestors increased, and the percentage of SNP with 1 missing allele was greater than that for 2 missing alleles for all scenarios. The largest numbers of conflicts were found between scenarios 1 and 3. The inclusion of information from direct ancestors (dam or sire) with US GDB genotypes in the imputation of Mexican Holstein genotypes increased imputation accuracy by 1 percentage point for low-density genotypes and by 0.5 percentage points for high-density genotypes, which was about half the gain found with information from all US GDB Holsteins. A larger reference population and the availability of genotyped ancestors improved imputation; animals with genotyped parents in a large reference population had higher imputation accuracy than those with no or few genotyped relatives in a small reference population. For small local populations, including genotypes from other related populations can aid in improving imputation accuracy.

Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

INTRODUCTION: At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. METHODS: A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. RESULTS: Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). CONCLUSIONS: Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system.

Effectiveness of 11C-choline PET/CT in prostate cancer surveillance.

AIM: Our aim was to analyse the performance of [11C]choline PET/CT in prostate cancer (PCa) surveillance, especially in patients with prostate specific antigen (PSA) < 1 ng/mL. MATERIAL AND METHODS: Three hundred and twenty-nine [11C]choline PET/CT examinations from 191 patients (68.2 ±â€¯7.2 years) submitted for PCa surveillance or biochemical recurrence were retrospectively evaluated. PSA at study was 13.0 ±â€¯84.2 ng/mL. Main initial treatment was radical prostatectomy (RP) in 81 patients, and other treatments (radiotherapy, chemotherapy, hormonotherapy) in 110. PET/CT was acquired 20' after injection of 555-740 MBq of [11C]choline. Minimum follow-up was 12 months. RESULTS: Two hundred and nineteen (66.6%) out of the 329 PET/CT examinations were positive. The percentage of positive examinations was significantly higher in patients with other initial treatment than RP compared to patients with RP (85.6% vs. 43.6%, respectively). One hundred and thirty PET/CT (59.4%) showed local recurrence, 48 (21.9%) distant recurrence, and 41 (18.7%) local plus distant recurrence. Initial therapeutic approach was changed in 139 cases (63.5%). In the subgroup of 81 [11C]choline PET/CT scans performed with PSA < 1 ng/mL, 23 (28.4%) showed a positive result. Initial therapeutic approach was changed in 9 (11.1%). Three (4.8%) out of 63 patients died as per PCa. CONCLUSION: [11C]choline PET/CT demonstrated its effectiveness in PCa surveillance and restaging, even in patients with serum PSA < 1 ng/mL. The diagnostic performance was different depending on the initial treatment, been higher in patients with non-surgical treatment.

Short communication: Estimation of ileal digestibility in chickens using single- and dual-tracer methods.

Fractionation of digesta, as occurs during gastrointestinal transit in chickens, complicates accurate measurements of ileal digestibility using tracers. Dual-tracer methods using separate tracers for solid and fluid digesta phases may improve the accuracy of digestibility measurements when assumptions of the single tracer method are violated. The aim of the present study was to compare the apparent ileal digestibility (AID) of nutrients calculated with single- and dual-tracer methods in chickens fed diets varying in particle size, anticipating digesta phase separation in the proximal gastrointestinal tract. A total of 112 Dekalb White (BW: 1.53 ± 0.107 kg) and 112 Bovans Black (BW: 1.79 ± 0.127 kg) 29-week-old laying hens were distributed over 32 pens (seven birds/pen). Within breed, pens were randomly assigned to one of two experimental diets (coarse vs fine oat hulls; n = 8 replicate pens per diet/breed combination). Diets were supplemented with TiO2 (3 g/kg) and Co-EDTA (2 g/kg). On days 34, 35, or 36, birds were euthanised and digesta from the ileum was collected for tracer and nutrient analyses. Apparent ileal digestibility was subsequently calculated by single- and dual-tracer methods. Although coarse oat hulls were hypothesised to increase the fractionation of solid and fluid digesta phases, no breed or diet × method interactions were found. Using a single tracer method based on TiO2, AID of nitrogen (N) was overestimated by 3%-units (P < 0.01) compared with the dual-tracer method, whereas AID estimates of DM, starch, fat, and non-starch polysaccharides did not differ (P > 0.09) and precision of all AID estimates was improved. In conclusion, these results show that although from a conceptual perspective, dual-tracer methods are presumed to better account for the variation in flow behaviour of different digesta phases, AID estimates obtained by the commonly used single tracer method using solid-phase tracer TiO2 were more precise and only marginally differed from estimates obtained by a dual-tracer method using distinct tracers for solid (TiO2) and liquid (Co-EDTA) digesta phases. Considering technical and economical constraints, the single tracer method may thus be the method of choice in many situations. Only when digestibility of proteins or amino acids is of specific interest, single tracer methods using a solid-phase tracer may not suffice. Nevertheless, for both single- and dual-tracer methods, tracer selection is critical, and the choice of tracers should depend on the nutrient(s) of interest.

A dynamic model to measure retention of solid and liquid digesta fractions in chickens fed diets with differing fibre sources.

Dietary fibres impact multiple digestive processes, and insights into the effects of various types of fibre on digesta retention time are required to optimise current feed formulation systems. Therefore, the objective of this study was to apply a dynamic modelling approach to generate estimates for the retention time of solid and liquid digesta in broilers fed different fibre sources. A maize-wheat-soybean meal control diet was compared against three diets in which wheat was partially substituted with oat hulls, rice husks, or sugar beet pulp (3% w/w). Non-starch polysaccharide (NSP) digestibility was evaluated in broilers between 23 and 25 days of age (n = 60 birds/treatment) using titanium dioxide (TiO2, 0.5 g/kg) as a marker, after feeding the experimental diets for 21 days. Digesta mean retention time (MRT) was measured in another 108 birds at 30 days of age by the administration of an oral pulse dose of chromium sesquioxide (Cr2O3) as solid marker and Cobalt-EDTA as liquid marker, and subsequent measurement of marker recovery in compartments of the digestive tract (n = 2 or 3 replicate birds/time point/treatment). Marker recovery models to estimate fractional passage rates for solid and liquid digesta in crop, gizzard, small intestine, and caeca compartments of the gastrointestinal tract were developed to predict MRT of solid and liquid digesta for each dietary treatment. The models were composed of a series of first-order differential equations, representing the variation of marker concentration in a compartment over time. Estimated MRT of solid and liquid digesta in the gizzard varied from 20 min for oat hulls and 34 min for rice husks diets to 14 min for sugar beet pulp and 12 min for control diets. In the caeca, liquid MRT was decreased compared to the control diet (989 min) for the sugar beet pulp diet (516 min), while it was increased for both the oat hulls and rice husks diets (≈1 500 min). Overall, these estimates are greater than those previously reported, suggesting that liquid digesta retention in the caeca previously has been underestimated. Digestibility of total NSP was increased by dietary fibre inclusion, regardless of the fibre type, although degradation of constituent sugars of NSP varied among diets. In conclusion, the inclusion of fibre sources at a low level (3% w/w) in the diet of broiler modulated retention time mainly in the gizzard and caeca, and increased digestibility of NSP.

Degradation of biogenic amines by vineyard ecosystem fungi. Potential use in winemaking.

AIMS: To evaluate the ability of grapevine ecosystem fungi to degrade histamine, tyramine and putrescine in synthetic medium and in wines. METHODS AND RESULTS: Grapevine and vineyard soil fungi were isolated from four locations of Spain and were subsequently identified by PCR. A total of 44 fungi were evaluated for in vitro amine degradation in a microfermentation system. Amine degradation by fungi was assayed by reversed-phase (RP)-HPLC. All fungi were able to degrade at least two different primary amines. Species of Pencillium citrinum, Alternaria sp., Phoma sp., Ulocladium chartarum and Epicoccum nigrum were found to exhibit the highest capacity for amine degradation. In a second experiment, cell-free supernatants of P. citrinum CIAL-274,760 (CECT 20782) grown in yeast carbon base with histamine, tyramine or putrescine, were tested for their ability to degrade amines in three different wines (red, white and synthetic). The highest levels of biogenic amine degradation were obtained with histamine-induced enzymatic extract. CONCLUSION: The study highlighted the ability of grapevine ecosystem fungi to degrade biogenic amines and their potential application for biogenic amines removal in wine. SIGNIFICANCE AND IMPACT OF STUDY: The fungi extracts described in this study may be useful in winemaking to reduce the biogenic amines content of wines, thereby preventing the possible adverse effects on health in sensitive individuals and the trade and export of wine.

Diffuse Large B-Cell Epstein-Barr Virus-Positive Primary CNS Lymphoma in Non-AIDS Patients: High Diagnostic Accuracy of DSC Perfusion Metrics.

BACKGROUND AND PURPOSE: Immunodeficiency-associated CNS lymphoma may occur in different clinical scenarios beyond AIDS. This subtype of CNS lymphoma is diffuse large B-cell and Epstein-Barr virus-positive. Its accurate presurgical diagnosis is often unfeasible because it appears as ring-enhancing lesions mimicking glioblastoma or metastasis. In this article, we describe clinicoradiologic features and test the performance of DSC-PWI metrics for presurgical identification. MATERIALS AND METHODS: Patients without AIDS with histologically confirmed diffuse large B-cell Epstein-Barr virus-positive primary CNS lymphoma (December 2010 to January 2022) and diagnostic MR imaging without onco-specific treatment were retrospectively studied. Clinical, demographic, and conventional imaging data were reviewed. Previously published DSC-PWI time-intensity curve analysis methodology, to presurgically identify primary CNS lymphoma, was used in this particular lymphoma subtype and compared with a prior cohort of 33 patients with Epstein-Barr virus-negative CNS lymphoma, 35 with glioblastoma, and 36 with metastasis data. Normalized curves were analyzed and compared on a point-by-point basis, and previously published classifiers were tested. The standard percentage of signal recovery and CBV values were also evaluated. RESULTS: Seven patients with Epstein-Barr virus-positive primary CNS lymphoma were included in the study. DSC-PWI normalized time-intensity curve analysis performed the best for presurgical identification of Epstein-Barr virus-positive CNS lymphoma (area under the receiver operating characteristic curve of 0.984 for glioblastoma and 0.898 for metastasis), followed by the percentage of signal recovery (0.833 and 0.873) and CBV (0.855 and 0.687). CONCLUSIONS: When a necrotic tumor is found in a potentially immunocompromised host, neuroradiologists should consider Epstein-Barr virus-positive CNS lymphoma. DSC-PWI could be very useful for presurgical characterization, with especially strong performance of normalized time-intensity curves.

The effect of added oat hulls or sugar beet pulp to diets containing rapidly or slowly digestible protein sources on broiler growth performance from 0 to 36 days of age.

The effects of formulating broiler diets that contain sources of either rapidly or slowly digestible protein and 2 different dietary fiber sources on growth performance were studied in broilers chickens from 0 to 36 d of age. A total of 1,920 one-day-old, male Ross 708 broiler chickens were randomly allocated and housed in 48 floor pens (40 birds/pen) to one of 4 dietary treatments. Birds were allotted according to a completely randomized block design using a factorial arrangement of treatments with 2 protein digestion rates (rapidly or slowly) and 2 dietary fiber sources [3% oat hulls (OH) or 3% sugar beet pulp (SBP)] from 0 to 36 d of age. All diets were formulated to be isocaloric and isonitrogenous. The pen was the experimental unit for all variables studied (12 replicates/treatment). Data were analyzed using the MIXED procedure of SAS, and the model included the main effects of the protein digestion rate, dietary fiber source, and their interaction. There were 3 experimental feeding phases; starter (from day 0-14), grower (from day 14-28), and finisher (from day 28-36). Results indicated that broilers fed diets containing sources that supplied more rapidly digestible protein had 4% greater (P < 0.01) ADG and improved (P < 0.01) the feed conversion ratio (FCR) by 5% throughout the experiment, most notably after the starter phase. Diets containing 3% OH increased (P < 0.05) the ADFI and ADG (P < 0.05) in the starter phase compared with broilers fed diets containing 3% SBP, without affecting the FCR. The ADG and FCR of broilers fed diets containing sources of slowly digestible protein were improved (P < 0.05) to the level of broilers fed rapidly digestible protein containing diets with the addition of 3% OH. It is concluded that broiler diets should be formulated to contain a high concentration of ingredients that supply rapidly digestible protein, but if this is cost-prohibitive, then 3% OH could be used to increase the ADFI and ADG and potentially protein digestion rates to reduce the FCR.

Presurgical Identification of Primary Central Nervous System Lymphoma with Normalized Time-Intensity Curve: A Pilot Study of a New Method to Analyze DSC-PWI.

BACKGROUND AND PURPOSE: DSC-PWI has demonstrated promising results in the presurgical diagnosis of brain tumors. While most studies analyze specific parameters derived from time-intensity curves, very few have directly analyzed the whole curves. The aims of this study were the following: 1) to design a new method of postprocessing time-intensity curves, which renders normalized curves, and 2) to test its feasibility and performance on the diagnosis of primary central nervous system lymphoma. MATERIALS AND METHODS: Diagnostic MR imaging of patients with histologically confirmed primary central nervous system lymphoma were retrospectively reviewed. Correlative cases of glioblastoma, anaplastic astrocytoma, metastasis, and meningioma, matched by date and number, were retrieved for comparison. Time-intensity curves of enhancing tumor and normal-appearing white matter were obtained for each case. Enhancing tumor curves were normalized relative to normal-appearing white matter. We performed pair-wise comparisons for primary central nervous system lymphoma against the other tumor type. The best discriminatory time points of the curves were obtained through a stepwise selection. Logistic binary regression was applied to obtain prediction models. The generated algorithms were applied in a test subset. RESULTS: A total of 233 patients were included in the study: 47 primary central nervous system lymphomas, 48 glioblastomas, 39 anaplastic astrocytomas, 49 metastases, and 50 meningiomas. The classifiers satisfactorily performed all bilateral comparisons in the test subset (primary central nervous system lymphoma versus glioblastoma, area under the curve = 0.96 and accuracy = 93%; versus anaplastic astrocytoma, 0.83 and 71%; versus metastases, 0.95 and 93%; versus meningioma, 0.93 and 96%). CONCLUSIONS: The proposed method for DSC-PWI time-intensity curve normalization renders comparable curves beyond technical and patient variability. Normalized time-intensity curves performed satisfactorily for the presurgical identification of primary central nervous system lymphoma.

Inactivation of oenological lactic acid bacteria (Lactobacillus hilgardii and Pediococcus pentosaceus) by wine phenolic compounds.

AIMS: To investigate the inactivation properties of different classes of phenolic compounds present in wine against two wine isolates of Lactobacillus hilgardii and Pediococcus pentosaceus, and to explore their inactivation mechanism. METHODS AND RESULTS: After a first screening of the inactivation potency of 21 phenolic compounds (hydroxybenzoic and hydroxycinnamic acids, phenolic alcohols, stilbenes, flavan-3-ols and flavonols) at specific concentrations, the survival parameters (MIC and MBC) of the most active compounds were determined. For the L. hilgardii strain, the flavonols morin and kaempferol showed the strongest inactivation (MIC values of one and 5 mg l(-1), and MBC values of 7.5 and 50 mg l(-1), respectively). For the P. pentosaceus strain, flavonols also showed the strongest inactivation effects, with MIC values between one and 10 mg l(-1) and MBC values between 7.5 and 300 mg l(-1). Observations by epifluorescence and scanning electron microscopy revealed that the phenolics damaged the cell membrane and promoted the subsequent release of the cytoplasm material into the medium. CONCLUSIONS: The antibacterial activity of wine phenolics against L. hilgardii and P. pentosaceus was dependent on the phenolic compound tested, and led not only to bacteria inactivation, but also to the cell death. SIGNIFICANCE AND IMPACT OF THE STUDY: New information about the inactivation properties of wine lactic acid bacteria by phenolic compounds is presented. It opens up a new area of study for selecting/obtaining wine phenolic preparations with potential applications as a natural alternative to SO(2) in winemaking.

Characterization of EHG Contractions at Pregnancy and Term Labor by Multiscale Entropy Analysis.

Monitoring uterine activity by electrohysterogram (EHG), associated with contractions both in pregnancy and labor, may contribute to the knowledge for evaluating possible risks to the binomial mother-fetus. In this context, the aim of the present study was to explore the complexity of EHG generated by women during the third trimester of pregnancy (group P) and at term labor (group L). The EHG was obtained by band-pass filtering in the range from 0.1 to 3 Hz the monopolar raw signal of the electrode number 1, of a 4-by-4 sensor array, which was located near to the tocodynamometer transducer. Multiscale entropy (MSE) analysis measures the entropy over multiple time scales to provide the complexity of the EHG time series. The results pointed out that such nonlinear technique has the potential to discriminate contractions from both groups using the area under the MSE curve (AUC) as index. The highest complexity was obtained for group P (N= 8) as AUC was 13.9233 ± 0.2015 while the lowest complexity was for group L, with N=8 and AUC of 5.1675 ± 0.0783 (p<; 0.0001). Consequently, the complexity of EHG by MSE could provide an index to discriminate between the electrical uterine activity generated during pregnancy or at labor.