Triterpene glycosides from Antarctic sea cucumbers. 1. Structure of liouvillosides A1, A2, A3, B1, and B2 from the sea cucumber Staurocucumis liouvillei: new procedure for separation of highly polar glycoside fractions and taxonomic revision

Five new triterpene glycosides, liouvillosides A1 (1), A2 (2), A3 (3), B1 (4), and B2 (5), have been isolated from the Antarctic sea cucumber Staurocucumis liouviellei along with the known liouvilloside A(6), isolated earlier from the same species, and hemoiedemosides A (7) and B (8), isolated earlier from the Patagonian sea cucumber Hemioedema spectabilis. The isolation was carried out using a new chromatographic procedure including application of ion-pair reversed-phase chromatography followed by chiral chromatography on a cyclodextrin ChiraDex column. The structures of the new glycosides were elucidated using extensive NMR spectroscopy (1H and 13C NMR spectrometry, DEPT, 1H-(1)H COSY, HMBC, HMQC, and NOESY), ESI-FTMS, and CID MS/MS, and chemical transformations. Glycosides 1-3 are disulfated tetraosides and glycosides 4 and 5 are trisulfated tetraosides. Glycosides 2 and 3 contain 3-O-methylquinovose, found for the first time as a natural monosaccharide in sea cucumber glycosides. On the basis of analyses of glycoside structures a taxonomic revision is proposed.     

Resting energy expenditure and body composition in bedridden institutionalized elderly women with advanced-stage pressure sores

BACKGROUND: Our study investigated nutritional status, body composition, and resting energy expenditure (REE) in elderly patients with advanced-stage pressure sores (PS), in addition to researching any hypermetabolic condition and its relationship with PS size. METHODS: The study involved 52 institutionalized bedridden elderly women (aged 83.7 +/- 6.3 years), divided into two groups: 23 with advanced-stage (stage 3 and 4) PS and 29 without PS. Albumin, prealbumin, and retinol-binding protein were measured in all patients, and fat-free mass (FFM) and fat mass (FM) were obtained by dual-energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry and predicted with the Harris-Benedict formula. PS area and volume were also measured. RESULTS: The elderly women with and without PS were comparable in age, FFM, and FM. Mean albumin, prealbumin, and retinol-binding protein values were lower in cases with PS. Unadjusted mean REE was significantly higher in patients with PS (1212.3 +/- 236.7 vs 1085.5 +/- 161.3 kcal/d; p <.05), even after adjusting for FFM or expressed per kilogram of body weight (25.8 +/- 6.7 vs 21.1 +/- 4.0 kcal/d/kg; p <.01). Hypermetabolism, i.e., a measured REE > 110% of the predicted REE, was seen in 74% of patients with PS and 38% of controls. The difference between measured and predicted REE (DeltaREE) correlated with PS volume (r = 0.58; p <.01), but not with area. CONCLUSION: Advanced-stage PS in elderly women are associated with a hypermetabolic state that is influenced by the volume of the PS.     

Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies

Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little is known about the underlying molecular mechanism by which risperidone acts. Although a number of genetic variants have been observed to correlate with treatment response there are no definitive predictors of response. We performed a genome-wide gene expression analysis (Human Genome U219 Array Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. Our results revealed that cellular risperidone treatment is associated with a range of gene expression changes, which are time (6–48 h) and dose related (0.1–10 μM). We found that functional clusters of these changes correspond to Gene Ontology categories related to neural cell development functions, and synaptic structure and functions. We also identified Canonical Pathways related to these functional categories: neurogenesis and axon guidance; synaptic vesicle; and neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we identified candidate genes for pharmacogenetic studies related to the main risperidone secondary effects: motor disorders, cardiovascular disorders and metabolic disorders. Our results suggest that risperidone treatment affects the neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement with the “initiation and adaptation” model to explain the mechanism of action of psychotropic drugs.     

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging

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The trade-off between formal and informal care in Spain

Understanding the factors that determine the type and amount of formal care is important for predicting use in the future and developing long-term policy. In this context, we jointly analyze the provision of care at both the extensive (choice of care) and the intensive margin (number of hours of care received). In particular, we estimate and test, for the first time in this area of research, a sample selection model with the particularities that the first step is a multinomial logit model and the hours of care is an interval variable. Our results support the complementary and task-specific models which evidence has been found in other countries. Furthermore, we obtain evidence of substitution between formal and informal care for the male, young, married and unmarried subsamples. Regarding the hours of care, we find significant biases in predicted hours of care when sample selection is not taken into account. For the whole sample, the average bias is 2.77% for total hours and 3.23% for formal care hours. However, biases can be much larger (up to 10–15%), depending on the subsample and the type of care considered.     

Breast Density Analysis Using an Automatic Density Segmentation Algorithm

Breast density is a strong risk factor for breast cancer. In this paper, we present an automated approach for breast density segmentation in mammographic images based on a supervised pixel-based classification and using textural and morphological features. The objective of the paper is not only to show the feasibility of an automatic algorithm for breast density segmentation but also to prove its potential application to the study of breast density evolution in longitudinal studies. The database used here contains three complete screening examinations, acquired 2 years apart, of 130 different patients. The approach was validated by comparing manual expert annotations with automatically obtained estimations. Transversal analysis of the breast density analysis of craniocaudal (CC) and mediolateral oblique (MLO) views of both breasts acquired in the same study showed a correlation coefficient of ρ = 0.96 between the mammographic density percentage for left and right breasts, whereas a comparison of both mammographic views showed a correlation of ρ = 0.95. A longitudinal study of breast density confirmed the trend that dense tissue percentage decreases over time, although we noticed that the decrease in the ratio depends on the initial amount of breast density.     

Mapping molecular binding by means of conformational dynamics measurements

Protein–protein interactions are key in virtually all biological processes. The study of these interactions and the interfaces that mediate them play a key role in the understanding of biological function. In particular, the observation of protein–protein interactions in their dynamic environment is technically difficult. Here two surface analysis techniques, dual polarization interferometry and quartz crystal microbalance with dissipation monitoring, were paired for real-time mapping of the conformational dynamics of protein–protein interactions. Our approach monitors this dynamics in real time and in situ, which is a great advancement within technological platforms for drug discovery. Results agree with the experimental observations of the interaction between the TRIM21α protein and circulating autoantibodies via a bridging bipolar mechanism. This work provides a new chip-based method to monitor conformational dynamics of protein–protein interactions, which is amenable to miniaturized high-throughput determination.

Protein–protein interactions are key in virtually all biological processes.     

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology

Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.