Investigating Mixture Interactions of Astringent Stimuli Using the Isobole Approach.

Astringents (alum, malic acid, tannic acid) representing 3 broad classes (multivalent salts, organic acids, and polyphenols) were characterized alone, and as 2- and 3-component mixtures using isoboles. In experiment 1, participants rated 7 attributes ("astringency," the sub-qualities "drying," "roughing," and "puckering," and the side tastes "bitterness," "sourness," and "sweetness") using direct scaling. Quality specific power functions were calculated for each stimulus. In experiment 2, the same participants characterized 2- and 3-component mixtures. Multiple factor analysis (MFA) and hierarchical clustering on attribute ratings across stimuli indicate "astringency" is highly related to "bitterness" as well as "puckering," and the subqualities "drying" and "roughing" are somewhat redundant. Moreover, power functions were used to calculate indices of interaction (I) for each attribute/mixture combination. For "astringency," there was evidence of antagonism, regardless of the type of mixture. Conversely, for subqualities, the pattern of interaction depended on the mixture type. Alum/tannic acid and tannic acid/malic acid mixtures showed evidence of synergy for "drying" and "roughing"; alum/malic acid mixtures showed evidence of antagonism for "drying," "roughing," and "puckering." Collectively, these data clarify some semantic ambiguity regarding astringency and its subqualities, as well as the nature of interactions of among different types of astringents. Present data are not inconsistent with the idea that astringency arises from multiple mechanisms, although it remains to be determined whether the synergy observed here might reflect simultaneous activation of these multiple mechanisms.

Salivary protein levels as a predictor of perceived astringency in model systems and solid foods.

Salivary protein difference value (SP D-value) is a quantitative measure of salivary protein replenishment, which reportedly relates to individual differences in perceived astringency. This in vitro measure is calculated as the difference in total salivary protein before (S1) and after (S2) stimulation with tannic acid, with a greater absolute value (S2-S1) indicating less protein replenishment. Others report that this measure predicts perceived astringency and liking of liquid model systems and beverages containing added polyphenols. Whether this relationship generalizes to astringent compounds other than polyphenols, or to solid foods is unknown. Here, the associations between SP D-values and perceived astringency and overall liking/disliking for alum and tannic acid (experiment 1) as well as solid chocolate-flavored compound coating with added tannic acid or grape seed extract (GSE) (experiment 2) were examined. In both experiments, participants (n=84 and 81, respectively) indicated perceived intensity of astringency, bitterness, sweetness, and sourness, and degree of liking of either aqueous solutions, or solid chocolate-flavored compound coating with added astringents. Data were analyzed via linear regression, and as discrete groups for comparison to prior work. Three discrete groups were formed based on first and third quartile splits of the SP D-value distribution: low (LR), medium (MR), and high responding (HR) individuals. In experiment 1, significantly higher mean astringency ratings were observed for the HR as compared to the LR/MR groups for alum and tannic acid, confirming and extending prior work. In experiment 2, significantly higher mean astringency ratings were also observed for HR as compared to LR groups in solid chocolate-flavored compound containing added tannic acid or GSE. Significant differences in liking were found between HR and LR groups for alum and tannic acid in water, but no significant differences in liking were observed for chocolate-flavored compound samples. A significant linear relationship between SP D-values and perceived astringency was observed for both alum and tannic acid (p's<0.001), although the variance explained was relatively low (R(2)=0.33 and 0.29, respectively). In the solid chocolate-flavored compound spiked with either tannic acid or GSE, the relationship was not significant (p=0.17 and 0.30; R(2)=0.03 and 0.02, respectively). Due to the weak associations overall, and the lack of significant differences in perception of astringency between the MR and LR groups, we conclude that SP D-values are not a strong predictor of astringency, especially in solid, high-fat foods. Additional research investigating alternative methods for quantifying individual differences in astringency, as well as exploring the underlying complexities of this percept appears warranted.

Check-All-That-Apply (CATA), Sorting, and Polarized Sensory Positioning (PSP) with Astringent Stimuli.

Multiple rapid sensory profiling techniques have been developed as more efficient alternatives to traditional sensory descriptive analysis. Here, we compare the results of three rapid sensory profiling techniques - check-all-that-apply (CATA), sorting, and polarized sensory positioning (PSP) - using a diverse range of astringent stimuli. These rapid methods differ in their theoretical basis, implementation, and data analyses, and the relative advantages and limitations are largely unexplored. Additionally, we were interested in using these methods to compare varied astringent stimuli, as these compounds are difficult to characterize using traditional descriptive analysis due to high fatigue and potential carry-over. In the CATA experiment, subjects (n=41) were asked to rate the overall intensity of each stimulus as well as to endorse any relevant terms (from a list of 13) which characterized the sample. In the sorting experiment, subjects (n=30) assigned intensity-matched stimuli into groups 1-on-1 with the experimenter. In the PSP experiment, (n=41) subjects first sampled and took notes on three blind references ('poles') before rating each stimulus for its similarity to each of the 3 poles. Two-dimensional perceptual maps from correspondence analysis (CATA), multidimensional scaling (sorting), and multiple factor analysis (PSP) were remarkably similar, with normalized RV coefficients indicating significantly similar plots, regardless of method. Agglomerative hierarchical clustering of all data sets using Ward's minimum variance as the linkage criteria showed the clusters of astringent stimuli were approximately based on the respective class of astringent agent. Based on the descriptive CATA data, it appears these differences may be due to the presence of side tastes such as bitterness and sourness, rather than astringent sub-qualities per se. Although all three methods are considered 'rapid,' our prior experience with sorting suggests it is best performed 1:1 with the experimenter, which makes sorting relatively less efficient than CATA or PSP. Based on the evaluation criteria used here, the choice of method depends on the time constraints of the experimenter and the need for descriptive terms to understand the sensory space of the samples. Accordingly, we recommend a mixed approach that combines CATA with a subsequent PSP task so that the product space can be well characterized before choosing poles for PSP.

Treatment strategy for a multidrug-resistant Klebsiella UTI.

OBJECTIVE: To describe the management strategy for a multidrug-resistant (MDR) Klebsiella urinary tract infection (UTI). CASE SUMMARY: A 69-year-old Caucasian woman with a past medical history of recurrent UTIs and a right-lung transplant presented with fever to 101.4°F, chills, malaise, and cloudy, foul-smelling urine for approximately 1 week. She was found to have a MDR Klebsiella UTI that was sensitive to tigecycline and cefepime. To further evaluate the degree of resistance Etest minimum inhibitory concentrations were requested for cefepime, amikacin, meropenem, and ertapenem. The patient received a 14-day course of amikacin, which resulted in resolution of her symptoms. One month later, the patient's UTI symptoms returned. The urine culture again grew MDR Klebsiella, sensitive only to tigecycline. Fosfomycin was initiated and resulted in limited resolution of her symptoms. Colistin was started, however, therapy was discontinued on day 5 secondary to the development of acute kidney injury. Despite the short course of therapy, the patient's symptoms resolved. DISCUSSION: The case presented lends itself well to numerous discussion items that are important to consider when determining optimal treatment for MDR Gram-negative bacilli (GNBs). Susceptibility testing is an important tool for optimizing antibiotic therapy, however, automated systems may overestimate the susceptibility profile for a MDR GNB. Treatment strategies evaluated to treat MDR GNB, include combination therapy with a carbepenem and synergy using polymyxin. CONCLUSION: We have described the management strategy for a MDR Klebsiella UTI, the consequences of the initial management strategy, and potential strategies to manage these types of infections in future patients.

Patterns of mineral lick visitation by spider monkeys and howler monkeys in Amazonia: are licks perceived as risky areas?

Mineral licks--also known as "salados," "saladeros," or "collpas"--are specific sites in tropical and temperate ecosystems where a large diversity of mammals and birds come regularly to feed on soil. Although the reasons for vertebrate geophagy are not completely understood, animals are argued to obtain a variety of nutritional and health benefits from the ingestion of soil at mineral licks. We studied the temporal patterns of mineral lick use by white-bellied spider monkey (Ateles belzebuth) and red howler monkey (Alouatta seniculus) in a lowland rain forest in Amazonian Ecuador. Using camera and video traps at four different mineral licks, combined with behavioral follows of one group of spider monkeys, we documented rates of mineral lick visitation by both primate species and the relative frequency and intensity of mineral lick use by spider monkeys. On the basis of 1,612 days and 888 nights of mineral lick monitoring, we found that A. belzebuth and A. seniculus both visit mineral licks frequently throughout the year (on average ∼14% of days for both species), and mineral lick visitation was influenced by short-term environmental conditions (e.g. sunny and dry weather). For spider monkeys, the area surrounding the lick was also the most frequently and most intensively used region within the group's home range. The fact that spider monkeys spent long periods at the lick area before coming to the ground to obtain soil, and the fact that both species visited the lick preferentially during dry sunny conditions (when predator detectability is presumed to be relatively high) and visited simultaneously more often than expected by chance, together suggest that licks are indeed perceived as risky areas by these primates. We suggest that howler and spider monkeys employ behavioral strategies aimed at minimizing the probability of predation while visiting the forest floor at risky mineral lick sites.

Protease inhibition in African subtypes of HIV-1.

Of the 42 million people infected with HIV-1 worldwide, 30 million are in Africa. However, the HIV-1 subtypes prevalent in Africa are not the same that are prevalent in North America and Western Europe. In these developed regions, subtype B is responsible for the vast majority of HIV infections, whereas in sub-Saharan Africa subtypes A and C, and to a lesser extent subtype G, account for most of the infections. These subtypes exhibit genomic differences as large as 30% with respect to subtype B. These differences involve current drug targets, including the HIV-1 protease. Since protease inhibitors have been developed and tested against the HIV-1 B subtype, and proteases from other subtypes carry up to ten amino acid polymorphisms, it is important to assess the influence of these naturally occurring polymorphisms on the potency of existing inhibitors, as well as their synergistic interactions with mutations known to cause drug resistance. This review will examine the effects of naturally occurring polymorphisms on the efficacy of current protease inhibitors and the effects of well characterized drug-resistant mutations within the framework of non-B subtypes. At the biochemical level, non-B-subtype polymorphisms lower the binding affinities of existing clinical inhibitors, but not to the point of causing drug resistance. However, these polymorphisms amplify the effects of mutations causing drug resistance and may play a role in the long-term viability of these inhibitors.