Acetate is a bioenergetic substrate for human glioblastoma and brain metastases.

Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using (13)C-NMR analysis of brain tumors resected from patients during infusion of (13)C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-(13)C]acetate and can do so while simultaneously oxidizing [1,6-(13)C]glucose. The tumors do not oxidize [U-(13)C]glutamine. In vivo oxidation of [1,2-(13)C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.

Comparison of Multiple NIR Spectrometers for Detecting Low-Concentration Nitrogen-Based Adulteration in Protein Powders.

Protein adulteration is a common fraud in the food industry due to the high price of protein sources and their limited availability. Total nitrogen determination is the standard analytical technique for quality control, which is incapable of distinguishing between protein nitrogen and nitrogen from non-protein sources. Three benchtops and one handheld near-infrared spectrometer (NIRS) with different signal processing techniques (grating, Fourier transform, and MEM-micro-electro-mechanical system) were compared with detect adulteration in protein powders at low concentration levels. Whey, beef, and pea protein powders were mixed with a different combination and concentration of high nitrogen content compounds-namely melamine, urea, taurine, and glycine-resulting in a total of 819 samples. NIRS, combined with chemometric tools and various spectral preprocessing techniques, was used to predict adulterant concentrations, while the limit of detection (LOD) and limit of quantification (LOQ) were also assessed to further evaluate instrument performance. Out of all devices and measurement methods compared, the most accurate predictive models were built based on the dataset acquired with a grating benchtop spectrophotometer, reaching R2P values of 0.96 and proximating the 0.1% LOD for melamine and urea. Results imply the possibility of using NIRS combined with chemometrics as a generalized quality control tool for protein powders.

The Effect of Aviva Exercise Intervention on Pain Level and Body Awareness in Women with Primary Dysmenorrhea.

Background and Objective: Primary dysmenorrhea (PD) is one of the most common clinical disorders in women of reproductive age. Our aim was to examine whether a twice-weekly thirty-minute Aviva exercise intervention could result in improvements in pain level and body awareness in patients with PD. Materials and Methods: In our prospective observational trial, the observation period included two consecutive menstrual cycles and the period of the next menstrual bleeding. The first menstrual bleeding period was the first measurement time (T1), the second was the second measurement time (T2), and the third was the third measurement time (T3) in a total of 78 volunteers. The primary endpoint was the change in the level of menstrual pain according to the Numeric Rating Scale (NRS) questionnaire between the intervention group (IG) and the control group (CG) at T1, T2, and T3. In this study, the secondary outcomes were the differences between the IG and CG regarding the different subscales of the Hungarian version of the Body Awareness Questionnaire (BAQ-H) at T1, T2, and T3; the Borg scale results of the IG; and adherence to the intervention. Statistical tests such as independent-sample t-tests, chi-square tests, Pearson's linear correlation coefficient, and repeated-measure ANCOVA were used for the analyses. Results: In total, 78 volunteers were enrolled: 40 persons in the IG and 38 in the CG. There was a significant change in the level of menstruation pain according to the NRS questionnaire between the IG and CG (p < 0.001). There was no significant difference between the IG and CG regarding the different subscales of the BAQ-H. Only in the case of the "Note responses or changes in body process" subscale of the BAQ-H was there a trend-like effect from the Aviva exercises (p = 0.086). Conclusions: The Aviva exercise could contribute to pain relief from PD. Regarding body awareness, no significant difference was found between the two groups. Due to the short detection period and prospective observational design, our results are preliminary and need to be confirmed in larger clinical trials.

J-Difference editing (MEGA) of lactate in the human brain at 3T.

PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.

Trends in artificial aroma sensing by means of electronic nose technologies to advance dairy production - a review.

Controversies surrounding the name and how the electronics nose (e-nose) works have been at the center stage since the advent of the technology. Notwithstanding the controversies, the technology has gained popularity in the sensory analysis of dairy foods, because of its rapid results delivery on product aroma profile or pattern, which can be used to assess quality. This review critically evaluated the advances made in the application of the e-nose or artificial sensory system in the dairy industry, focusing on the evaluation of milk, yoghurt and cheese properties, and the trends and prospects of the technology. Most of the e-nose devices applied in the available scientific publications used sensors such as metal oxide semiconductor sensors (MOS), metal-oxide-semiconductor field-effect transistor (MOSFET), conducting polymers composites and quartz microbalance (QMB), and flame ionization detector FID, in a recent study. Though known for aroma sensing, the technology has been applied to evaluate the shelf life or microbial spoilage and to discriminate dairy products based on the volatile profile composition, as determined by the sensors. In most cases, the limitation of the technology is the inability of it to provide information on the nature of constituting compounds, except in gas chromatography and mass spectrometry-based e-nose systems.

Phase separation by ssDNA binding protein controlled via protein-protein and protein-DNA interactions.

Bacterial single-stranded (ss)DNA-binding proteins (SSB) are essential for the replication and maintenance of the genome. SSBs share a conserved ssDNA-binding domain, a less conserved intrinsically disordered linker (IDL), and a highly conserved C-terminal peptide (CTP) motif that mediates a wide array of protein-protein interactions with DNA-metabolizing proteins. Here we show that the Escherichia coli SSB protein forms liquid-liquid phase-separated condensates in cellular-like conditions through multifaceted interactions involving all structural regions of the protein. SSB, ssDNA, and SSB-interacting molecules are highly concentrated within the condensates, whereas phase separation is overall regulated by the stoichiometry of SSB and ssDNA. Together with recent results on subcellular SSB localization patterns, our results point to a conserved mechanism by which bacterial cells store a pool of SSB and SSB-interacting proteins. Dynamic phase separation enables rapid mobilization of this protein pool to protect exposed ssDNA and repair genomic loci affected by DNA damage.

Application of Near Infrared Spectroscopy to Monitor the Quality Change of Sour Cherry Stored under Modified Atmosphere Conditions.

Determining and applying 'good' postharvest and quality control practices for otherwise highly sensitive fruits, such as sour cherry, is critical, as they serve as excellent media for a wide variety of microbial contaminants. The objective of this research was to report two series of experiments on the modified atmosphere storage (MAP) of sour cherries (Prunus cerasus L. var. Kántorjánosi, Újfehértói fürtös). Firstly, the significant effect of different washing pre-treatments on various quality indices was examined (i.e., headspace gas composition, weight loss, decay rate, color, firmness, soluble solid content, total plate count) in MAP-packed fruits. Subsequently, the applicability of near infrared (NIR) spectroscopy combined with chemometrics was investigated to detect the effect of various storage conditions (packed as control or MAP, stored at 3 or 5 °C) on sour cherries of different perceived ripeness. Significant differences were found for oxygen concentration when two perforations were applied on the packages of 'Kántorjánosi' (p < 0.01); weight loss when 'Kánorjánosi' (p < 0.001) and 'Újfehértói fürtös' (p < 0.01) were packed in MAP; SSC when 'Újfehértói fürtös' samples were ozone-treated (p < 0.05); and total plate count when 'Kántorjánosi' samples were ozone-treated (p < 0.01). The difference spectra reflected the high variability in the samples, and the detectable effects of different packaging. Based on the investigations with the soft independent modelling of class analogies (SIMCA), different packaging and storage resulted in significant differences in most of the cases even on the first storage day, which in many cases increased by the end of storage. The soft independent modelling of class analogies proved to be suitable for classification with apparent error rates between 0 and 0.5 during prediction regardless of ripeness. The research findings suggest the further correlation of NIR spectroscopic and reference parameters to support postharvest handling and fast quality control.

StereoPHIP: Stereoselective Parahydrogen-Induced Polarization.

Parahydrogen-induced polarization (PHIP) followed by polarization transfer to 13 C is a rapidly developing technique for the generation of 13 C-hyperpolarized substrates. Chirality plays an essential role in living systems and differential metabolism of enantiomeric pairs of metabolic substrates is well documented. Inspired by asymmetric hydrogenation, here we report stereoPHIP, which involves the addition of parahydrogen to a prochiral substrate with a chiral catalyst followed by polarization transfer to 13 C spins. We demonstrate that parahydrogen could be rapidly added to the prochiral precursor to both enantiomers of lactic acid (D and L), with both the (R,R) and (S,S) enantiomers of a chiral rhodium(I) catalyst to afford highly 13 C-hyperpolarized (over 20 %) L- and D-lactate ester derivatives, respectively, with excellent stereoselectivity. We also show that the hyperpolarized 1 H signal decays obtained with the (R,R) and (S,S) catalysts were markedly different. StereoPHIP expands the scope of conventional PHIP to the production of 13 C hyperpolarized chiral substrates with high stereoselectivity.

The recent advances of near-infrared spectroscopy in dairy production-a review.

One of the major issues confronting the dairy industry is the efficient evaluation of the quality of feed, milk and dairy products. Over the years, the use of rapid analytical methods in the dairy industry has become imperative. This is because of the documented evidence of adulteration, microbial contamination and the influence of feed on the quality of milk and dairy products. Because of the delays involved in the use of wet chemistry methods during the evaluation of these products, rapid analytical techniques such as near-infrared spectroscopy (NIRS) has gained prominence and proven to be an efficient tool, providing instant results. The technique is rapid, nondestructive, precise and cost-effective, compared with other laboratory techniques. Handheld NIRS devices are easily used on the farm to perform quality control measures on an incoming feed from suppliers, during feed preparation, milking and processing of cheese, butter and yoghurt. This ensures that quality feed, milk and other dairy products are obtained. This review considers research articles published in reputable journals which explored the possible application of NIRS in the dairy industry. Emphasis was on what quality parameters were easily measured with NIRS, and the limitations in some instances.

Revealing the Effect of Heat Treatment on the Spectral Pattern of Unifloral Honeys Using Aquaphotomics.

In this study we aimed to investigate the effect of heat treatment on the spectral pattern of honey using near infrared spectroscopy (NIRS). For the research, sunflower, bastard indigo, and acacia honeys were collected from entrusted beekeepers. The honeys were not subject to any treatment before. Samples were treated at 40 °C, 60 °C, 80 °C, and 100 °C for 60, 120, 180, and 240 min. This resulted in 17 levels, including the untreated control samples. The 5-hydroxymethylfurfural (HMF) content of the honeys was determined using the Winkler method. NIRS spectra were recorded using a handheld instrument. Data analysis was performed using ANOVA for the HMF content and multivariate analysis for the NIRS data. For the latter, PCA, PCA-LDA, and PLSR models were built (using the 1300-1600 nm spectral range) and the wavelengths presenting the greatest change induced by the perturbations of temperature and time intervals were collected systematically, based on the difference spectra and the weights of the models. The most contributing wavelengths were used to visualize the spectral pattern changes on the aquagrams in the specific water matrix coordinates. Our results showed that the heat treatment highly contributed to the formation of free or less bonded water, however, the changes in the spectral pattern highly depended on the crystallization phase and the honey type.

NIRS and Aquaphotomics Trace Robusta-to-Arabica Ratio in Liquid Coffee Blends.

Coffee is both a vastly consumed beverage and a chemically complex matrix. For a long time, an arduous chemical analysis was necessary to resolve coffee authentication issues. Despite their demonstrated efficacy, such techniques tend to rely on reference methods or resort to elaborate extraction steps. Near infrared spectroscopy (NIRS) and the aquaphotomics approach, on the other hand, reportedly offer a rapid, reliable, and holistic compositional overview of varying analytes but with little focus on low concentration mixtures of Robusta-to-Arabica coffee. Our study aimed for a comparative assessment of ground coffee adulteration using NIRS and liquid coffee adulteration using the aquaphotomics approach. The aim was to demonstrate the potential of monitoring ground and liquid coffee quality as they are commercially the most available coffee forms. Chemometrics spectra analysis proved capable of distinguishing between the studied samples and efficiently estimating the added Robusta concentrations. An accuracy of 100% was obtained for the varietal discrimination of pure Arabica and Robusta, both in ground and liquid form. Robusta-to-Arabica ratio was predicted with R2CV values of 0.99 and 0.9 in ground and liquid form respectively. Aquagrams results accentuated the peculiarities of the two coffee varieties and their respective blends by designating different water conformations depending on the coffee variety and assigning a particular water absorption spectral pattern (WASP) depending on the blending ratio. Marked spectral features attributed to high hydrogen bonded water characterized Arabica-rich coffee, while those with the higher Robusta content showed an abundance of free water structures. Collectively, the obtained results ascertain the adequacy of NIRS and aquaphotomics as promising alternative tools for the authentication of liquid coffee that can correlate the water-related fingerprint to the Robusta-to-Arabica ratio.

Recent developments in microbial production of high-purity galacto-oligosaccharides.

Galacto-oligosaccharides (GOS) are used as prebiotic ingredients in various food and pharmaceutical formulations. Currently, production of GOS involves the enzymatic conversion of lactose by transgalactosylation using ß-galactosidase. The purity of the resulting product is low, typically limited to up to 55% GOS on total carbohydrate basis due to the presence of non-reacted lactose, and the formation of by-products glucose and galactose. In industrial practice high-purity GOS is manufactured by removing the unwanted mono- and disaccharides from raw GOS with simulated moving bed (SMB) chromatography. This purification step is associated with high processing cost that increases the price of pure GOS and limits its marketability. The last decades have witnessed a growing interest in developing competitive biotechnological processes that could replace chromatography. This paper presents a comprehensive review on the recent advancements of microbial GOS purification, a process commonly referred to as selective fermentation or selective metabolism. Purification strategies include: (i) removal of glucose alone or together with galactose by lactose negative yeast species, that typically results in purity values below 60% due to remaining lactose; (ii) removal of both mono- and disaccharides by combining the fast monosaccharide metabolizing capacity of some yeast species with efficient lactose consumption by certain lactose positive microbes, reaching GOS purity in the range of 60-95%; and (iii) the application of selected strains of Kluyveromyces species with high lactose metabolizing activity to achieve high-purity GOS that is practically free from lactose and monosaccharides.

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-13 C]-l-lactate.

PURPOSE: To evaluate the utility of hyperpolarized [1-13 C]-l-lactate to detect hepatic pyruvate carboxylase activity in vivo under fed and fasted conditions. METHODS: [1-13 C]-labeled sodium L-lactate was polarized using a dynamic nuclear polarizer. Polarization level and the T1 were measured in vitro in a 3 Telsa MR scanner. Two groups of healthy rats (fasted vs. fed) were prepared for in vivo studies. Each rat was anesthetized and intravenously injected with 60-mM hyperpolarized [1-13 C]-l-lactate, immediately followed by dynamic acquisition of 13 C (carbon-13) MR spectra from the liver at 3 Tesla. The dosage-dependence of the 13 C-products was also investigated by performing another injection of an equal volume of 30-mM hyperpolarized [1-13 C]-l-lactate. RESULTS: T1 and liquid polarization level of [1-13 C]-l-lactate were estimated as 67.8 s and 40.0%, respectively. [1-13 C]pyruvate and [1-13 C]alanine, [13 C]bicarbonate ( HCO3- ) and [1-13 C]aspartate were produced from hyperpolarized [1-13 C]-l-lactate in rat liver. Smaller HCO3- and larger aspartate were measured in the fed group compared to the fasted group. Pyruvate and alanine production were increased in proportion to the lactate concentration, whereas the amount of HCO3- and aspartate production was consistent between 30-mM and 60-mM lactate injections. CONCLUSION: This study demonstrates that a unique biomarker of pyruvate carboxylase flux, the appearance of [1-13 C]aspartate from [1-13 C]-l-lactate, is sensitive to nutritional state and may be monitored in vivo at 3 Tesla. Because [13 C] HCO3- is largely produced by pyruvate dehydrogenase flux, these results suggest that the ratio of [1-13 C]aspartate and [13 C] HCO3- (aspartate/ HCO3- ) reflects the saturable pyruvate carboxylase/pyruvate dehydrogenase enzyme activities.

Quality assessment of a consultation-liaison psychiatry service.

BACKGROUND: Consultation-Liaison Psychiatry (CLP) provides services for patients with medical-psychiatric comorbidity at the general hospital. Referral satisfaction is considered as one of the most important outcome measures of CLP interventions. Our aim was to assess the levels of satisfaction with the CLP service amongst medical staff at a university hospital in Denmark. METHODS: Medical staff answered an online survey regarding their experience with different aspects of inpatient and outpatient CLP services. RESULTS: There were 152 responses from 16 medical units, with a survey return rate above 85%. Measured on a 5-point Likert scale, there was a median rating of 4 in response to questions regarding communication and organizational aspects, a median rating of 5 in response to questions regarding overall evaluation of the CLP service on both inpatient and outpatient questionnaire. The questions regarding treatment quality were rated with a median of 4 on the inpatient questionnaire and 2 of the outpatient questionnaire items, and with a median of 5 on 2 outpatient items. Physicians´ evaluations were statistically more positive than nurses´. As a group, respondents already employed before the CLP unit was established and those who used the CLP services more were statistically significantly more satisfied then respondents employed after the establishment of the CLP unit and those who used the CLP service less. CONCLUSION: The CLP services were positively appreciated and considered to be valuable among medical hospital staff. We believe that Consultation-Liaison Psychiatry deserves further help to implement and expand its services in general hospital settings. In addition, our results underline the feasibility of surveys as quality measures of clinical care.

Standardized Extraction Techniques for Meat Analysis with the Electronic Tongue: A Case Study of Poultry and Red Meat Adulteration.

The electronic tongue (e-tongue) is an advanced sensor-based device capable of detecting low concentration differences in solutions. It could have unparalleled advantages for meat quality control, but the challenges of standardized meat extraction methods represent a backdrop that has led to its scanty application in the meat industry. This study aimed to determine the optimal dilution level of meat extract for e-tongue evaluations and also to develop three standardized meat extraction methods. For practicality, the developed methods were applied to detect low levels of meat adulteration using beef and pork mixtures and turkey and chicken mixtures as case studies. Dilution factor of 1% w/v of liquid meat extract was determined to be the optimum for discriminating 1% w/w, 3% w/w, 5% w/w, 10% w/w, and 20% w/w chicken in turkey and pork in beef with linear discriminant analysis accuracies (LDA) of 78.13% (recognition) and 64.73% (validation). Even higher LDA accuracies of 89.62% (recognition) and 68.77% (validation) were achieved for discriminating 1% w/w, 3% w/w, 5% w/w, 10% w/w, and 20% w/w of pork in beef. Partial least square models could predict both sets of meat mixtures with good accuracies. Extraction by cooking was the best method for discriminating meat mixtures and can be applied for meat quality evaluations with the e-tongue.

Near-Infrared Spectroscopy and Aquaphotomics for Monitoring Mung Bean (Vigna radiata) Sprout Growth and Validation of Ascorbic Acid Content.

Mung bean is a leguminous crop with specific trait in its diet, namely in the form of anti-nutrient components. The sprouting process is commonly done for better nutritional acceptance of mung bean as it presents better nutritional benefits. Sprouted mung bean serves as a cheap source of protein and ascorbic acid, which are dependent on the sprouting process, hence the importance of following the biological process. In larger production scale, there has not been a definite standard for mung bean sprouting, raising the need for quick and effective mung bean sprout quality checks. In this regard, near-infrared spectroscopy (NIRS) has been recognized as a highly sensitive technique for quality control that seems suitable for this study. The aim of this paper was to describe quality parameters (water content, pH, conductivity, and ascorbic acid by titration) during sprouting using conventional analytical methods and advanced NIRS techniques as correlative methods for modelling sprouted mung beans' quality and ascorbic acid content. Mung beans were sprouted in 6 h intervals up to 120 h and analyzed using conventional methods and a NIR instrument. The results of the standard analytical methods were analyzed with univariate statistics (analysis of variance (ANOVA)), and the NIRS spectral data was assessed with the chemometrics approach (principal component analysis (PCA), discriminant analysis (DA), and partial least squares regression (PLSR)). Water content showed a monotonous increase during the 120 h of sprouting. The change in pH and conductivity did not describe a clear pattern during the sprouting, confirming the complexity of the biological process. Spectral data-based discriminant analysis was able to distinctly classify the bean sprouts with 100% prediction accuracy. A NIRS-based model for ascorbic acid determination was made using standard ascorbic acid to quantify the components in the bean extract. A rapid detection technique within sub-percent level was developed for mung bean ascorbic acid content with R2 above 0.90. The NIR-based prediction offers reliable estimation of mung bean sprout quality.

2,3-Dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8b)-ones: Synthesis, Structure and DFT Study on the Mechanism of Chemo- and Diastereoslective Annulations of (Sp)-2-Formylferrocenecarbonyl Fluoride and (Sp)-2-Formylferrocenecarboxylic Acid.

By means of the annulation of easy-to-handle yet sufficiently reactive (Sp)-2-formylferrocenecar- bonyl fluoride with the hydrochlorides of cysteamine and the methyl esters of enentiomer cysteines conducted in dichloromethane at room temperature in the presence of pyridine, the first members of 2,3-dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8bH)-ones with the elements of planar- and central chirality were prepared as single enantiomers. An atom economic procedure was also elaborated for the synthesis of these organometallic heterocycles directly exploring (Sp)-2-formylferrocenecarboxylic acid in situ activated by CDI and TFA, sequentially added to the reaction mixture. The relative and consequently, the absolute, configuration of the isolated diastereomers was determined by NMR measurements supported by DFT structural optimization. On the basis of the results of synthetic control experiments and a series of further DFT modelling studies, including energetic and MO analysis of the iminium intermediates, we propose a mechanism for the thiazolidine-forming annulations that proceed via primary N-acylation followed by proton-mediated cyclocondensation and subsequent diastereoselective sulfhydryl-attack on the resulting iminium center.

Origin Identification of Hungarian Honey Using Melissopalynology, Physicochemical Analysis, and Near Infrared Spectroscopy.

The objective of the study was to check the authenticity of Hungarian honey using physicochemical analysis, near infrared spectroscopy, and melissopalynology. In the study, 87 samples from different botanical origins such as acacia, bastard indigo, rape, sunflower, linden, honeydew, milkweed, and sweet chestnut were collected. The samples were analyzed by physicochemical methods (pH, electrical conductivity, and moisture), melissopalynology (300 pollen grains counted), and near infrared spectroscopy (NIRS:740-1700 nm). During the evaluation of the data PCA-LDA models were built for the classification of different botanical and geographical origins, using the methods separately, and in combination (low-level data fusion). PC number optimization and external validation were applied for all the models. Botanical origin classification models were >90% and >55% accurate in the case of the pollen and NIR methods. Improved results were obtained with the combination of the physicochemical, melissopalynology, and NIRS techniques, which provided >99% and >81% accuracy for botanical and geographical origin classification models, respectively. The combination of these methods could be a promising tool for origin identification of honey.

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo.

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

Simultaneous Assessment of Intracellular and Extracellular pH Using Hyperpolarized [1-13C]Alanine Ethyl Ester.

Tissue pH is tightly regulated in vivo, being a sensitive physiological biomarker. Advent of dissolution dynamic nuclear polarization (DNP) and its translation to humans stimulated development of pH-sensitive agents. However, requirements of DNP probes such as biocompatibility, signal sensitivity, and spin-lattice relaxation time (T1) complicate in vivo translation of the agents. Here, we developed a 13C-labeled alanine derivative, [1-13C]-l-alanine ethyl ester, as a viable DNP probe whose chemical shift is sensitive to the physiological pH range, and demonstrated the feasibility in phantoms and rat livers in vivo. Alanine ethyl ester readily crosses cell membrane while simultaneously assessing extracellular and intracellular pH in vivo. Following cell transport, [1-13C]-l-alanine ethyl ester is instantaneously hydrolyzed to [1-13C]-l-alanine, and subsequently metabolized to [1-13C]lactate and [13C]bicarbonate. The pH-insensitive alanine resonance was used as a reference.