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According to Stephen Finlay, ' A ought to X ' means that X -ing is more conducive to contextually salient ends than relevant alternatives. This in turn is analysed in terms of probability. I show why this theory of 'ought' is hard to square with a theory of a reason's weight which could explain why ' A ought to X ' logically entails that the balance of reasons favours that A X -es. I develop two theories of weight to illustrate my point. I first look at the prospects of a theory of weight based on expected utility theory. I then suggest a simpler theory. Although neither allows that ' A ought to X ' logically entails that the balance of reasons favours that A X -es, this price may be accepted. For there remains a strong pragmatic relation between these claims.

Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar "Merton Russet" and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar "Cox's Orange Pippin" and were not detected in the waxy apple cultivar "Royal Gala". High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both "Merton Russet" and "Royal Gala" trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-κB activation with IC50's of 6-9 μM. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 μM in the in vitro and ex vivo bioassays, boosting production of the pro-inflammatory cytokine TNFα in cells stimulated with bacterial lipopolysaccharides.

Rapid and direct, in situ headspace screening for odoriferous volatile organic compounds (VOCs) present in fresh grapes and in wines is a very promising method for quality control because the economic value of a wine is closely related to its aroma. Long used for the detection of VOCs in complex mixtures, miniature differential ion mobility spectrometry (DMS) seems therefore adequate for in situ trace detection of many kinds of VOCs of concern appearing in the headspace of selected foodstuffs. This work aims at a rapid detection, identification, and quantification of some natural and volatile contaminants of wine such as geosmin, 2-methylisoborneol (2-MIB), 1-octen-3-ol, 1-octen-3-one, and pyrazines (2-isopropyl-3-methoxypyrazine, IPMP, and 3-isobutyl-2-methoxypyrazine, IBMP). In the present study, these compounds were spiked at a known concentration in wine and analyzed with a hyphenated trap-GC-DMS device. The detection of all target compounds at concentrations below the human olfactory threshold was demonstrated.

Aim: To assess national trends over time in surgery for elderly patients with resectable breast cancer (BC) and to evaluate clinical outcome and cause of death after the omission of surgery in a regional cohort of elderly patients., Methods: National trends in 1995-2005 were calculated using cancer registry data. In addition, a chart review was performed in a cohort of patients aged ≥ 75 years, with early stage BC but no primary surgery, diagnosed at five Dutch hospitals in 1990-2005. Patient characteristics, comorbidity and reason for the omission of surgery were collected from the chart. Cause of death was retrieved from death certificate data registered at Statistics Netherlands., Results: Omission of surgery increased significantly over time for patients aged 80 years and older (p<0.05). Of the 187 patients in the regional cohort (median age 85.9 years (range 75.0-97.7), 174 (92%) received hormonal therapy. Omission of surgery was at the patient's request in 59 patients (32%). Of the 178 patients that died during follow-up, 60 patients (34%) died of BC. For 81 patients (45%), BC was not clinically relevant at the time of death. Median overall survival was 2.3 years (range 0.2-10.7) and did not differ between BC and other causes of death (p=0.9)., Conclusion: Omission of surgery for elderly patients with resectable BC has increased significantly over the past decade; instead patients often received primary endocrine treatment. Although this may appear an effective alternative to surgery, the potential for a longer term negative impact on disease control and quality of life deserves further investigation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: There is an increasing trend for optical guidance techniques in surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can distinguish different tissue types through a specific "optical fingerprint". We investigated whether DRS could discriminate metastatic tumor tissue from normal liver tissue and thus if this technique would have potential for further implementation into surgical instruments or radiological intervention tools., Methods: A miniaturized optical needle was developed able to collect DRS spectra between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal liver metastases were analyzed with DRS immediately after resection. Multiple measurements were performed and DRS results were compared to the histology analysis of the measurement locations. In addition, normal liver tissue was scored for the presence or absence of steatosis., Results: A total of 780 out of the 828 optical measurements were correctly classified into either normal or tumor tissue. The resulting sensitivity and specificity were both 94%. The results of the analysis for each patient individually showed an accuracy of 100%. The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis in liver tissue compared to that of the pathologist was 0.86., Conclusions: DRS demonstrates a high accuracy in discriminating normal liver tissue from colorectal liver metastases. DRS can also predict the degree of hepatic steatosis with high accuracy. The technique, here demonstrated in a needle like probe, may as such be incorporated into surgical tools for optical guided surgery or percutaneous needles for radiological interventions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The polyphenol (phenolic acids, flavanols and flavonols) and glycoalkaloid (α-chaconine and α-solanine) contents of potato tubers grown in Luxembourg were analyzed by UPLC-DAD and HPLC-MS/MS separately in peel (approx. 2mm), outer (approx. 1cm) and inner flesh. Polyphenol contents decreased from the peel via the outer to the inner flesh and differed among the cultivars. The cultivars Vitelotte and Luminella had the highest polyphenol contents (5202 and 572 μg/g dry weight (DW) in the outer flesh), whereas Charlotte and Bintje had the lowest contents (19.5 and 48.0 μg/g DW). Chlorogenic acid and its isomers (neo- and cryptochlorogenic acid) were the major polyphenols. Glycoalkaloid contents were highest in the peel and lowest in the inner flesh, values in the flesh were below guideline limits in all cultivars. In conclusion, potatoes contribute to the daily intake of polyphenols and their consumption, thereby, may have positive effects on health., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Potato is one of the most important staple food in the world because it is a good source of vitamin C, vitamin B6 but also an interesting source of minerals including mainly potassium, but also magnesium, phosphorus, manganese, zinc and iron to a lesser extent. The lack of iron constitutes the main form of micronutrient deficiency in the world, namely iron deficiency anemia, which strongly affects pregnant women and children from developing countries. Iron biofortification of major staple food such as potato is thus a crucial issue for populations from these countries. To better understand mechanisms leading to iron accumulation in potato, we followed in an in vitro culture experiment, by qPCR, in the cultivar Désirée, the influence of media iron content on the expression of genes related to iron uptake, transport and homeostasis. As expected, plantlets grown in a low iron medium (1 mg L(-1) FeNaEDTA) displayed a decreased iron content, a strong induction of iron deficiency-related genes and a decreased expression of ferritins. Inversely, plantlets grown in a high iron medium (120 mg L(-1) FeNaEDTA) strongly accumulated iron in roots; however, no significant change in the expression of our set of genes was observed compared to control (40 mg L(-1) FeNaEDTA)., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

We evaluated the potential of apple to reduce inflammation. Phenolic compounds and triterpenes were analyzed in 109 apple cultivars. Total phenolics ranged from 29 to 7882 μg g(-1) of fresh weight (FW) in the flesh and from 733 to 4868 μg g(-1) FW in the skin, with flavanols including epicatechin and procyanidins as major components. Ursolic (44.7 to 3522 μg g(-1) FW) and oleanolic (47.2 to 838 μg g(-1) FW) acids dominated the skin triterpene profile. Five chemically contrasting cultivars were fractionated and their immune-modulating activity measured using two cell-based assays targeting key points in the inflammation process. Cultivars exhibiting high contents of procyanidins were the most potent at inhibiting NF-κB while triterpene-rich fractions reduced the promoter activity of the gene of TNFα. This study provides new insights into how apple genetic diversity could be used to alleviate inflammation.

MERGANSER (MERcury Geo-spatial AssessmeNtS for the New England Region) is an empirical least-squares multiple regression model using mercury (Hg) deposition and readily obtainable lake and watershed features to predict fish (fillet) and common loon (blood) Hg in New England lakes. We modeled lakes larger than 8 ha (4404 lakes), using 3470 fish (12 species) and 253 loon Hg concentrations from 420 lakes. MERGANSER predictor variables included Hg deposition, watershed alkalinity, percent wetlands, percent forest canopy, percent agriculture, drainage area, population density, mean annual air temperature, and watershed slope. The model returns fish or loon Hg for user-entered species and fish length. MERGANSER explained 63% of the variance in fish and loon Hg concentrations. MERGANSER predicted that 32-cm smallmouth bass had a median Hg concentration of 0.53 μg g(-1) (root-mean-square error 0.27 μg g(-1)) and exceeded EPA's recommended fish Hg criterion of 0.3 μg g(-1) in 90% of New England lakes. Common loon had a median Hg concentration of 1.07 μg g(-1) and was in the moderate or higher risk category of >1 μg g(-1) Hg in 58% of New England lakes. MERGANSER can be applied to target fish advisories to specific unmonitored lakes, and for scenario evaluation, such as the effect of changes in Hg deposition, land use, or warmer climate on fish and loon mercury.

Potato can suffer from several abiotic stresses such as cold temperature, high soil salinity, lack of water or heavy metal exposure, to name a few. They are known to affect plant growth as well as productivity, with differential regulations at several levels. Potato response to cold and salt exposure was investigated at both transcriptomic and proteomic levels in a growth chamber experiment. Cold exposure in potato resulted in a higher number of significantly differentially regulated genes compared to salt exposure, whereas there were nearly three times more differentially regulated proteins after salt exposure when compared to cold exposure. The allocation of up and down-regulated genes at the functional category level also differed between salt and cold exposure although common trends, previously described in various abiotic stresses, were observed. In both stresses, the majority of photosynthesis-related genes were down-regulated whereas cell rescue and transcription factor-related genes were mostly up-regulated. In the other functional categories no common trend was observed; salt exposure results displayed a strong down-regulation of genes implicated in primary metabolism, detoxication apparatus and signal transduction, whereas upon cold exposure, up and down-regulated genes were similar in number. At the proteomic level, the abundance of the majority of identified proteins was increased except for the photosynthesis-related proteins, which were mostly less abundant after both salt and cold exposure. Common responses between salt and cold stress and specific responses inherent to these abiotic stresses are described.

We studied the spatial distribution patterns of mercury (Hg) in lake water, littoral sediments, zooplankton, crayfish, fish, and common loons in 44 lakes of the Adirondacks of New York State, USA, a region that has been characterized as a "biological Hg hotspot". Our study confirmed this pattern, finding that a substantial fraction of the lakes studied had fish and loon samples exceeding established criteria for human and wildlife health. Factors accounting for the spatial variability of Hg in lake water and biota were lake chemistry (pH, acid neutralizing capacity (ANC), percent carbon in sediments), biology (taxa presence, trophic status) and landscape characteristics (land cover class, lake elevation). Hg concentrations in zooplankton, fish and common loons were negatively associated with the lake water acid-base status (pH, ANC). Bioaccumulation factors (BAF) for methyl Hg (MeHg) increased from crayfish (mean log(10) BAF = 5.7), to zooplankton (5.9), to prey fish (6.2), to larger fish (6.3), to common loons (7.2). MeHg BAF values in zooplankton, crayfish, and fish (yellow perch equivalent) all increased with increasing lake elevation. Our findings support the hypothesis that bioaccumulation of MeHg at the base of the food chain is an important controller of Hg concentrations in taxa at higher trophic levels. The characteristics of Adirondack lake-watersheds (sensitivity to acidic deposition; significant forest and wetland land cover; and low nutrient inputs) contribute to elevated Hg concentrations in aquatic biota.

In potatoes and many other crops, drought is one of the most important environmental constraints leading to yield loss. Development of drought-tolerant cultivars is therefore required for maintaining yields under climate change conditions and for the extension of agriculture to sub-optimal cropping areas. Drought tolerance mechanisms have been well described for many crop plants including Native Andean potato. However, knowledge on tolerance traits suitable for commercial potato varieties is scarce. In order to describe drought tolerance mechanisms that sustain potato yield under water stress, we have designed a growth-chamber experiment with two Solanum tuberosum L. cultivars, the more drought tolerant accession 397077.16, and the sensitive variety Canchan. After 21 days of drought exposure, gene expression was studied in leaves using cDNA microarrays. The results showed that the tolerant clone presented more differentially expressed genes than the sensitive one, suggesting greater stress response and adaptation. Moreover, it exhibited a large pool of upregulated genes belonging to cell rescue and detoxication such as LEAs, dehydrins, HSPs, and metallothioneins. Transcription factors related to abiotic stresses and genes belonging to raffinose family oligosaccharide synthesis, involved in desiccation tolerance, were upregulated to a greater extent in the tolerant clone. This latter result was corroborated by biochemical analyses performed at 32 and 49 days after drought that showed an increase in galactinol and raffinose especially in clone 397077.16. The results depict key components for the drought tolerance of this advanced potato clone.

Small fruits such as berries have low energy contents, but high contents of vitamins, micronutrients, and dietary fibers and constitute a good source of natural antioxidant compounds that are important constituents of the human diet. This study identified a large number of compounds in an extract of black currant showing high antioxidant activity and compared their profile in various parts of the plants (leaves, buds, and berries). If it was known that berries contained very high levels of natural phenolic compounds, this study showed that leaves and buds could also be considered good sources of natural antioxidants. Indeed, they contained high amounts of phenolic acids, flavonoids, and carotenoids. An acetone mixture can extract several classes of phenolic compounds with a good yield of flavonols, flavan-3-ols, and anthocyanins.

Background: The incidence of ovarian metastases at the time of peritoneal carcinomatosis, and the influence of such metastases on survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), are unknown., Methods: This retrospective analysis included 194 women subjected to CRS and HIPEC since 2001. The incidence of ovarian metastases, disease-free survival and disease-specific survival were analysed., Results: The histological diagnosis was colorectal cancer carcinomatosis in 108 patients, peritoneal mucinous carcinomatosis (PMCA) in 23 and disseminated peritoneal adenomucinosis (DPAM) in 63. Ninety-nine patients underwent oophorectomy during the HIPEC procedure. Ovarian metastases were confirmed in at least 52 per cent of the patients. There was a significant difference in disease-free survival between women with or without ovarian metastases in both PMCA and DPAM groups (P = 0·044 and P = 0·010 respectively). No significant differences in survival were found in the group with colorectal cancer carcinomatosis., Conclusion: When peritoneal carcinomatosis of colorectal or appendiceal origin is confirmed, at least 52 per cent of ovaries will have synchronous metastases. Disease-free survival after a HIPEC procedure for PMCA or DPAM is significantly lower in women with ovarian metastases. Oophorectomy during CRS for peritoneal carcinomatosis should be strongly considered.

Background: Delayed gastric emptying (DGE) is a main complication with unknown origin after a cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS-HIPEC). The aim of this study was to investigate if preservation of the right gastro-epiploic artery (GEA) during standard omentectomy would have a positive effect on gastric emptying after CRS-HIPEC., Methods: Forty-two patients subjected to a CRS-HIPEC were randomized into two groups perioperatively before performing an omentectomy: in Group I (N = 21) omentectomy was performed with preservation of the GEA; in Group II (N = 21) omentectomy was performed with resection of the GEA. The primary endpoint was the number of days to full oral intake of solid food. Secondary endpoints were number of days to intended occlusion of gastrostomy catheter and total hospital admission time., Results: No significant differences were discovered between both groups in any of the study endpoints after CRS-HIPEC. No significant differences were observed in patient or operation characteristics between the randomized groups., Conclusions: No association was demonstrated between preservation of the gastro-epiploic artery during omentectomy and gastric emptying after CRS-HIPEC. The extensive intestinal manipulation or the heated intra-peritoneal chemotherapy during surgery are more plausible causes of this phenomenon. This clinical trial was registered in the Netherlands at the Central Committee on Research involving Human Subjects (CCMO) under registration number P06.0301L., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Between July 18(th) and 24(th) 2010, 26 leading microbial ecology, computation, bioinformatics and statistics researchers came together in Snowbird, Utah (USA) to discuss the challenge of how to best characterize the microbial world using next-generation sequencing technologies. The meeting was entitled "Terabase Metagenomics" and was sponsored by the Institute for Computing in Science (ICiS) summer 2010 workshop program. The aim of the workshop was to explore the fundamental questions relating to microbial ecology that could be addressed using advances in sequencing potential. Technological advances in next-generation sequencing platforms such as the Illumina HiSeq 2000 can generate in excess of 250 billion base pairs of genetic information in 8 days. Thus, the generation of a trillion base pairs of genetic information is becoming a routine matter. The main outcome from this meeting was the birth of a concept and practical approach to exploring microbial life on earth, the Earth Microbiome Project (EMP). Here we briefly describe the highlights of this meeting and provide an overview of the EMP concept and how it can be applied to exploration of the microbiome of each ecosystem on this planet.

Two potato clones (Solanum tuberosum L.) of the Andean cultivar group, called Sullu and SS2613, with different drought-tolerance phenotypes were exposed to a continuously increasing drought stress in a field trial. At the physiological level, while relative leaf water contents were similar in both clones, osmotic potential was lower in Sullu and declined more strongly during drought compared with SS2613. In the drought-stressed plants, tuber yield was reduced by about 70% compared with control plants in both clones. Potato cDNA microarrays and target metabolite analysis were performed on leaves sampled at several time-points after the onset of drought. At the transcriptomic level, photosynthesis-related genes were already strongly repressed in Sullu after 28 d of withholding irrigation and even more strongly after a longer stress duration, whereas, in SS2613, repression occurred only after 49 d of soil drying; similarly, a strong perturbation of carbohydrate-related genes was observed in Sullu. At the metabolite level, differential accumulation of osmotically active solutes was observed between the two cultivars; indeed, in Sullu, contents of galactose, inositol, galactinol, proline, and proline analogues were higher upon drought stress compared with SS2613. These results point to different drought responses in the cultivars at the leaf level, with, however, similar tuber yield reductions. The previously shown tolerant clone Sullu lost part of its tolerance under the experimental conditions used here; it was, however, able to maintain an absolute yield three times higher than SS2613.

The molecular response to salt exposure was studied in the leaves of a Solanum tuberosum clone using cDNA microarray. Differentially expressed genes were classified according to their known or predicted function and their expression ratio as compared to the control. The major changes upon a 150 mM NaCl exposure in potato leaves occurred in the photosystem apparatus and Calvin cycle: many transcripts coding for proteins belonging to photosystems I and II and chlorophyll synthesis were repressed. On the other hand, we observed the induction of various kinds of transcription factors implicated in osmotic stress response via ABA-dependent or ABA-independent pathways but also in plant defense pathways. This revealed a crosstalk between abiotic and biotic stress responses during salt exposure, which activated several adaptation mechanisms including heat shock proteins, late embryogenesis abundant, dehydrins and PR proteins. Gene expression changes related to carbohydrate and amino acid metabolism were also observed, pointing at putative modifications at the metabolic level.

Abstract Fixation with formaldehyde is the first process to which most biopsy and necropsy specimens are exposed prior to dehydration and embedding in paraffin wax. Tissue specimens that have been fixed in formaldehyde have architectural characteristics that are familiar to virtually every pathologist and these facilitate routine diagnosis. Nevertheless, formaldehyde fixation has some deleterious effects including reduction in immunoreactivity and degradation of nucleic acids. Development of methods to counteract these deleterious effects requires an understanding of the chemical events that occur during tissue fixation and subsequent tissue processing. This short review illustrates some of the chemical consequences of formaldehyde fixation and ethanol dehydration. It also provides some insight into the molecular events accompanying heat-induced antigen retrieval.

Polyphenols represent a large family of plant secondary metabolites implicated in the prevention of various diseases such as cancers and cardiovascular diseases. The potato is a significant source of polyphenols in the human diet. In this study, we examined the expression of thirteen genes involved in the biosynthesis of polyphenols in potato tubers using real-time RT-PCR. A selection of five field grown native Andean cultivars, presenting contrasting polyphenol profiles, was used. Moreover, we investigated the expression of the genes after a drought exposure. We concluded that the diverse polyphenolic profiles are correlated to variations in gene expression profiles. The drought-induced variations of the gene expression was highly cultivar-specific. In the three anthocyanin-containing cultivars, gene expression was coordinated and reflected at the metabolite level supporting a hypothesis that regulation of gene expression plays an essential role in the potato polyphenol production. We proposed that the altered sucrose flux induced by the drought stress is partly responsible for the changes in gene expression. This study provides information on key polyphenol biosynthetic and regulatory genes, which could be useful in the development of potato varieties with enhanced health and nutritional benefits.

The effects of drought stress on dietary antioxidant and glycoalkaloid contents in potato tubers were investigated using a selection of five native Andean cultivars. Both freshly harvested and 4 month-stored tubers were analyzed. Responses to drought stress were highly cultivar-specific. The antioxidant contents of the yellow tuber-bearing cultivars (Sipancachi and SS-2613) were weakly affected by the drought treatment, whereas the pigmented cultivars demonstrated highly cultivar-dependent variations. A drastic reduction of anthocyanins and other polyphenols was revealed in the red- (Sullu) and purple-fleshed (Guincho Negra) cultivars, whereas an increase was shown in the purple-skinned and yellow-fleshed cultivar (Huata Colorada). The hydrophilic antioxidant capacity (evaluated by Folin-Ciocalteu and H-oxygen radical absorbance capacity assays) was highly correlated with the polyphenol content and followed, therefore, the same behavior upon drought. Carotenoid contents, including beta-carotene, as well as vitamin E, tended to increase or remain stable following drought exposure, except for the cultivar Sullu, in which the level of these lipophilic antioxidants was decreased. Vitamin C contents were not affected by drought with the exception of Guincho Negra, in which the level was increased. These variations of health-promoting compounds were associated with increased or stable levels of the toxic glycoalkaloids, alpha-solanine and alpha-chaconine. Storage at 10 degrees C for 4 months tended to decrease the concentrations of all dietary antioxidants, except those of vitamin E. This storage also reduced the drought-induced variations observed in freshly harvested tubers. These results were discussed in terms of their implications for human diet and health as well as in plant stress defense mechanisms.

The antioxidant profile of 23 native Andean potato cultivars has been investigated from a human nutrition perspective. The main carotenoid and tocopherol compounds were studied using high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) and a fluorescence detector, respectively, whereas polyphenols (including anthocyanins in colored tubers) were identified by means of both HPLC-mass spectrometry and HPLC-DAD. Antioxidant profiling revealed significant genotypic variations as well as cultivars of particular interest from a nutritional point of view. Concentrations of the health-promoting carotenoids, lutein and zeaxanthin, ranged from 1.12 to 17.69 microg g(-1) of dry weight (DW) and from 0 to 17.7 microg g(-1) of DW, with cultivars 704353 and 702472 showing the highest levels in lutein and zeaxanthin, respectively. Whereas beta-carotene is rarely reported in potato tubers, remarkable levels of this dietary provitamin A carotenoid were detected in 16 native varieties, ranging from 0.42 to 2.19 microg g(-1) of DW. The amounts of alpha-tocopherol found in Andean potato tubers, extending from 2.73 to 20.80 microg g(-1) of DW, were clearly above the quantities generally reported for commercial varieties. Chlorogenic acid and its isomers dominated the polyphenolic profile of each cultivar. Dark purple-fleshed tubers from the cultivar 704429 contained exceptionally high levels of total anthocyanins (16.33 mg g(-1) of DW). The main anthocyanin was identified as petanin (petunidin-3-p-coumaroyl-rutinoside-5-glucoside). The results suggest that Andean potato cultivars should be exploited in screening and breeding programs for the development of potato varieties with enhanced health and nutritional benefits.

Background: Although mental stress is commonly considered to be an important trigger factor for migraine, experimental evidence for this belief is yet lacking., Objective: To study the temporal relationship between changes in stress-related parameters (both subjective and objective) and the onset of a migraine attack., Methods: This was a prospective, ambulatory study in 17 migraine patients. We assessed changes in perceived stress and objective biological measures for stress (saliva cortisol, heart rate average [HRA], and heart rate variability [low-frequency power and high-frequency power]) over 4 days prior to the onset of spontaneous migraine attacks. Analyses were repeated for subgroups of patients according to whether or not they felt their migraine to be triggered by stress., Results: There were no significant temporal changes over time for the whole group in perceived stress (p=0.50), morning cortisol (p=0.73), evening cortisol (p=0.55), HRA (p=0.83), low-frequency power (p=0.99) and high-frequency power (p=0.97) prior to or during an attack. Post hoc analysis of the subgroup of nine stress-sensitive patients who felt that >2/3 of their migraine attacks were triggered by psychosocial stress, revealed an increase for perceived stress (p=0.04) but no changes in objective stress response measures. At baseline, this group also showed higher scores on the Penn State Worry Questionnaire (p=0.003) and the Cohen Perceived Stress Scale (p=0.001) compared to non-stress-sensitive patients., Conclusions: Although stress-sensitive patients, in contrast to non-stress-sensitive patients, may perceive more stress in the days before an impending migraine attack, we failed to detect any objective evidence for a biological stress response before or during migraine attacks.

Potato tubers were evaluated as a source of antioxidants and minerals for the human diet. A genetically diverse sample of Solanum tuberosum L. cultivars native to the Andes of South America was obtained from a collection of nearly 1000 genotypes using microsatellite markers. This size-manageable collection of 74 landraces, representing at best the genetic diversity among potato germplasm, was analyzed for iron, zinc, calcium, total phenolic, total carotenoid, and total vitamin C contents. The hydrophilic antioxidant capacity of each genotype was also measured using the oxygen radical absorbance capacity (ORAC) assay. The iron content ranged from 29.87 to 157.96 microg g-1 of dry weight (DW), the zinc content from 12.6 to 28.83 microg g-1 of DW, and the calcium content from 271.09 to 1092.93 microg g-1 of DW. Total phenolic content varied between 1.12 and 12.37 mg of gallic acid equiv g-1 of DW, total carotenoid content between 2.83 and 36.21 microg g-1 of DW, and total vitamin C content between 217.70 and 689.47 microg g-1 of DW. The range of hydrophilic ORAC values was 28.25-250.67 micromol of Trolox equiv g-1 of DW. The hydrophilic antioxidant capacity and the total phenolic content were highly and positively correlated (r = 0.91). A strong relationship between iron and calcium contents was also found (r = 0.67). Principal component analysis on the studied nutritional contents of the core collection revealed that most potato genotypes were balanced in terms of antioxidant and mineral contents, but some of them could be distinguished by their high level in distinct micronutrients. Correlations between the micronutrient contents observed in the sample and the genetic distances assessed by microsatellites were weakly significant. However, this study demonstrated the wide variability of health-promoting micronutrient levels within the native potato germplasm as well as the significant contribution that distinct potato tubers may impart to the intake in dietary antioxidants, zinc, and iron.

Migraine attacks are often preceded by premonitory symptoms. Prevalence rates of migraine patients reporting one or more premonitory symptoms show considerable variability and rates range between 12% and 79%. Sources of variability might be differences in study population or research design. Using a questionnaire, we retrospectively studied the prevalence of 12 predefined premonitory symptoms in a clinic-based population. Of 461 migraine patients, 374 (81%) responded. At least one premonitory symptom was reported by 86.9% and 71.1% reported two or more. The most frequently reported premonitory symptoms were fatigue (46.5%), phonophobia (36.4%) and yawning (35.8%). The mean number of premonitory symptoms per person was 3.2 (+/- 2.5). Women reported 3.3 premonitory symptoms compared with 2.5 symptoms in men (P = 0.01). Age, education, migraine subtype (with or without aura) and mean attack frequency had no effect on the mean number of symptoms per individual. In conclusion, premonitory symptoms are frequently reported by migraine patients. Sensitivity and specificity of premonitory symptoms for migraine need to be assessed using prospective methods.

During embryonic development, the common pulmonary vein (PV) becomes incorporated into the left atrium, giving rise to separate PV ostia. We describe the consequences of this incorporation process for the histology of the left atrium and the possible clinical implications. The histology of the left atrial (LA) wall in relation to PV incorporation was studied immunohistochemically in 16 human embryos and fetuses, 1 neonate, and 5 adults. The PV wall, surrounded by extrapericardially differentiated myocardial cells, was incorporated into the LA body. After incorporation, the composition of PVs and the smooth-walled LA body wall was histologically identical. The LA appendage, however, consisted of endocardial and myocardial layers without a vessel wall component. In 2 adults, the myocardium in the LA posterior wall was absent. At the transition of the LA body and LA appendage, a smooth-walled myocardial zone lacking the venous wall was observed. This zone was histologically identical to the sinus venarum of the right atrium. In conclusion, the LA body arises by incorporation and growth of PVs, presenting with a histologically identical structure of vessel wall covered by extrapericardially differentiated myocardium of PVs. Discontinuity of myocardium may be the substrate for arrhythmias, and absence of myocardium in some patients makes this area potentially vulnerable to damage inflicted by ablation strategies. A border zone between the LA body and LA appendage is hypothesized to be the left part of the embryonic sinus venosus.

Plant stress studies are more and more based on gene expression. The analysis of gene expression requires sensitive, precise, and reproducible measurements for specific mRNA sequences. Real-time RT-PCR is at present the most sensitive method for the detection of low abundance mRNA. To avoid bias, real-time RT-PCR is referred to one or several internal control genes, which should not fluctuate during treatments. Here, the non-regulation of seven housekeeping genes (beta-tubulin, cyclophilin, actin, elongation factor 1-alpha (ef1alpha), 18S rRNA, adenine phosphoribosyl transferase (aprt), and cytoplasmic ribosomal protein L2) during biotic (late blight) and abiotic stresses (cold and salt stress) was tested on potato plants using geNorm software. Results from the three experimental conditions indicated that ef1alpha was the most stable among the seven tested. The expression of the other housekeeping genes tested varied upon stress. In parallel, a study of the variability of expression of hsp20.2, shown to be implicated in late blight stress, was realized. The relative quantification of the hsp20.2 gene varied according to the internal control and the number of internal controls used, thus highlighting the importance of the choice of internal controls in such experiments.

Background: Coronary artery disease represents a significant cause of morbidity and mortality in patients with connective tissue disease. Few reports exist on the results of surgical management of coronary artery disease in these patients., Methods: The medical records of patients with connective tissue diseases who underwent coronary artery bypass grafting at our institution between 1995 and 2002 were reviewed for demographic data, perioperative variables, and postoperative complications. The results were compared with data from The Society of Thoracic Surgeons database., Results: Forty-four patients were identified from a total of 5,496 cases during the study period (0.8%). There were 35 patients with rheumatoid arthritis, 8 with systemic lupus erythematosus, and 1 with scleroderma. Patients with connective tissue diseases were more likely to be women and use immunomodulating agents. They also had a higher incidence of Canadian Cardiovascular Society class IV angina, need for inotropic agents, need for intraaortic balloon pulsation, use of blood transfusions, and leg wound infections. The use of steroids or other immunomodulating agents was associated with increased postoperative complications. Mean follow-up was 35 months. The overall survival and freedom from reintervention at 3 years were 89% and 75%, respectively., Conclusions: Coronary artery bypass grafting is a safe treatment modality in patients with connective tissue diseases, with acceptable early results. Wound complications may be a problem in this patient population. Midterm results are less favorable, and reinterventions are frequently required.

Objectives: Patients with hematologic malignancies are frequently in need of major cardiac operations. Previous reports suggest an increased risk for perioperative complications in these immunodeficient patients., Methods: Patients diagnosed with any type of hematologic malignancy who underwent open-heart surgery at our institution between 7/1996 and 6/2002 were identified. Their hospital charts were reviewed; demographics, perioperative data and outcomes were recorded., Results: There were 24 patients (20 men, 4 women); mean age was 68+/-13 years (range 31-84 years). Ten patients had chronic lymphocytic leukemia, seven non-Hodgkin lymphomas, three multiple myeloma and one Hodgkin's disease, chronic myelocytic leukemia, hairy cell leukemia and cutaneous T-cell lymphoma each. The mean pre-operative duration of the hematologic disease was 6.6 years. Twenty-two patients underwent coronary artery bypass grafting (with valve replacement in three patients) and two patients had isolated valve replacement. There was one in-hospital death (4.1%). Twelve patients (50%) had a minor or major complication. Seven reoperations were required-five during the same admission (one for mediastinal bleeding, one for an expanding femoral pseudoaneurysm, one for acute cholecystitis and two for IACD/pacer insertion) and two within 30 days (one for deep sternal wound infection and one for leg wound infection). Mean post-operative stay was 8.2+/-5.8 days and mean ICU stay was 1.6+/-1.1 days. There were three late deaths-two were due to progression of the hematologic disease. The 3-year actuarial survival was 83%., Conclusions: Cardiac operations can be performed with acceptable mortality but significant morbidity rates in patients with hematologic malignancies. Bleeding and infectious complications are most frequently seen and usually lead to reoperations. These findings warrant caution during patient selection.

Horizontal resistance to late blight in the potato is a primary objective of many breeding programs. Knowledge of the physiological and biochemical mechanisms underlying it, however, is scarce. The purpose of the present study was the identification of these physiological and biochemical factors in plant material obtained by crossing a late blight resistant Solanum phureja clone with a susceptible dihaploid of S. tuberosum subsp. tuberosum. The mRNA RT-PCR differential display method was used to compare the gene expression patterns of a resistant hybrid with that of a susceptible one. By sequence homology, we identified several genes with diverse functions, including genes known to be involved in resistance or stress responses and genes known to be involved in primary or secondary metabolism.

Increased anthropogenic mercury (Hg) deposition since pre-industrial times, and subsequent transformation of inorganic Hg to methylmercury (MeHg) in aquatic environments, has created areas in North America where Hg poses a relatively high risk to wildlife, especially long-lived, piscivorous species. From 1995 to 2001, we opportunistically collected 577 eggs abandoned by Common Loons from eight states. Egg-Hg concentrations ranged from 0.07 to 4.42 microg/g (ww) or 0.10 to 19.40 microg/g (dw). Mercury was higher in eastern than in western North America. Female blood-Hg concentrations strongly correlated with those of eggs from the same territory even though the mean intraclutch Hg difference was 25%. In New England, egg volume declined significantly as egg-Hg concentrations increased. Fertility was not related to egg-Hg concentrations. Based on existing literature and this study's findings, egg-Hg risk levels were established and applied to our US data set and an existing Canadian data set. Regionally, we found the greatest risk levels in northeastern North America. With few exceptions, loon eggs are suitable indicators of methylmercury availability on lakes with territorial pairs.

Mercury and selenium act as mutual antagonists in mature birds, but their toxicity is additive or synergistic in avian embryos and immature birds. Twenty eggs and livers from 18 mature and 9 immature common loon carcasses found in Minnesota were collected. Livers and eggs were analyzed for mercury and selenium by atomic emission and atomic absorption spectroscopy. Liver mercury concentrations were significantly higher in mature loons compared to those of immature loons and eggs. Liver selenium concentrations were significantly higher in mature loons than those of immature loons, and selenium concentrations in immature loon livers were significantly higher than levels in eggs. There was a significant positive correlation between mercury and selenium in loon livers. There was a negative correlation between mercury and selenium in eggs.

This article describes an educational intervention designed to increase maternal knowledge and understanding of the need for, and timing of, childhood immunizations and to clarify misconceptions about vaccine efficacy and safety. A pamphlet was used as a method of imparting pertinent information about childhood immunization to mothers in the early postpartum period. Strategies known to be effective for women with low literacy levels were used in the pamphlet's design. It was piloted as an adjunct discharge teaching tool with 10 mothers in a large Southern teaching hospital in the United States. The pamphlet's use was openly received, considered effective, and endorsed by the mothers and nursing staff. The pamphlet is easy to use and duplicate, and can serve as a future resource to mothers after discharge. Because the problem of childhood underimmunization continues to be a serious concern for specific populations, it is essential that mothers have access to information that is concise, user friendly, and written at their level of understanding.

Issues and Purpose: Despite numerous programs aimed at improving immunization rates among American children, under-immunization remains a significant problem. This study was conducted to gain insight into parents'/guardians' knowledge and attitudes regarding childhood immunizations., Design and Methods: Thirteen African-American mothers and grandmothers participated in semistructured, audiotaped focus-group interviews., Results: Four major themes emerged: health knowledge and beliefs about immunizations, system barriers that impede obtaining immunizations, facilitators that enhance obtaining immunizations, and suggestions for change., Practice Implications: Immunizations are one of the most important health advantages available to children. Therefore, nurses must become aware of the problem of underimmunization and work to address some of the concerns caregivers have identified in this study. The health and lives of the nation's children depend on it.

In woody plants, chilling stress occurs during the early spring growth and can have important economic consequences. The aim of this study was to compare the reliability of two different experimental systems, 3-month-old softwood cuttings and in vitro-grown shoots, to study chilling effects in a poplar clone (Populus tremula×P. tremuloides cv. Muhs1). Different parameters were recorded: lignin content, sucrose concentration and protein and fresh weight variation, during a 2-week treatment at 10  °C. Two families of polypeptides of high molecular weight (110 and 116 kDa) were shown to accumulate in response to chilling in both cuttings and microshoots. For some of the parameters studied, i.e. appearance of some groups of polypeptides and reduction of fresh weight gain, both in vitro and ex vitro systems were suitable and produced similar results. In contrast, for some other observations, i.e. on sucrose concentration and lignin content, the systems led to different conclusions. While sucrose and lignin contents were shown to increase in cuttings submitted to chilling, no variation in lignin and only a small temporary peak of sucrose could be observed in microshoots kept under chilling. These parameters seem not to be suitable for studying the response of poplar in the in vitro system in such a short-term study.

Attaining full immunization coverage, particularly for those younger than 2 years of age, is a critical investment in the well-being and future of this nation's children. Unfortunately, not all children receive this health protective intervention equally or on a timely basis. The measles epidemic of 1989-1991 caused much concern to providers, parents, and government officials and focused the spotlight on this major healthcare issue. Those involved began to question the adequacy of federal immunization laws and the effectiveness of existing immunization programs. This article examines both significant former healthcare policy/legislation focused on childhood immunizations and current concerns regarding childhood immunizations in the United States, and offers a broad range of suggestions for future policy/practice modifications to address these concerns.

Two glycopeptides were synthesized by attaching purified glycosylamines (N-glycans) to a 20 amino acid peptide. Triantennary and Man9 Boc-tyrosinamide N-glycans were treated with trifluoroacetic acid to remove the Boc group and expose a tyrosinamide amine. The amine group was coupled with iodoacetic acid to produce N-iodoacetyl-oligosaccharides. These were reacted with the sulfhydryl group of a cysteine-containing peptide (CWK18), resulting in the formation of glycopeptides in good yield that were characterized by 1H NMR and ESIMS. Both glycopeptides were able to bind to plasmid DNA and form DNA condensates of approximately 110 nm mean diameter with zeta potential of +31 mV. The resulting homogeneous glycopeptide DNA condensates will be valuable as receptor-mediated gene-delivery agents.

Two poly(ethylene glycol) (PEG)-peptides were synthesized and tested for their ability to bind to plasmid DNA and form soluble DNA condensates with reduced spontaneous gene expression. PEG-vinyl sulfone or PEG-orthopyridyl disulfide were reacted with the sulfhydryl of Cys-Trp-Lys(18) (CWK(18)) resulting in the formation of nonreducible (PEG-VS-CWK(18)) and reducible (PEG-SS-CWK(18)) PEG-peptides. Both PEG-peptides were prepared on a micromole scale, purified by RP-HPLC in >80% yield, and characterized by (1)H NMR and MALDI-TOF. PEG-peptides bound to plasmid DNA with an apparent affinity that was equivalent to alkylated (Alk)CWK(18), resulting in DNA condensates with a mean diameter of 80-90 nm and zeta (zeta) potential of +10 mV. The particle size of PEG-peptide DNA condensates was constant throughout the DNA concentration range of 0. 05-2 mg/mL, indicating these to be approximately 20-fold more soluble than AlkCWK(18) DNA condensates. The spontaneous gene transfer to HepG2 cells mediated by PEG-VS-CWK(18) DNA condensates was over two orders of magnitude lower than PEG-SS-CWK(18) DNA condensates and three orders of magnitude lower than AlkCWK(18) DNA condensates. PEG-VS-CWK(18) efficiently blocked in vitro gene transfer by reducing cell uptake. The results indicate that a high loading density of PEG on DNA is necessary to achieve highly soluble DNA condensates that reduce spontaneous in vitro gene transfer by blocking nonspecific uptake by HepG2 cells. These two properties are important for developing targeted gene delivery systems to be used in vivo.

The N-linked oligosaccharide from soy bean agglutinin (Man9) was isolated on a preparative scale following derivatization with Boc-tyrosine. The procedure utilized preparative hydrazinolysis to release the oligosaccharide and yielded multi-micromol quantities of Boc-tyrosine-Man9 which was characterized by 1H NMR and ES-MS., (Copyright 1998 Academic Press.)

We present a new probabilistic model of evolution of RNA-, DNA-, or protein-like sequences and a tool rose that implements this model. By insertion, deletion and substitution of characters, a family of sequences is created from a common ancestor. During this artificial evolutionary process, the "true" history is logged and the "correct" multiple sequence alignment is created simultaneously. We also allow for varying rates of mutation within the sequences making it possible to establish so-called sequence motifs. The results are suitable for the evaluation of methods in multiple sequence alignment computation and the prediction of phylogenetic relationships.

The whole cell vaccine (WCV) of Bordetella pertussis is protective in the intracerebral (i.c.) mouse protection assay. We found a correlation between the i.c. mouse protection assay potency and the presence of the virulence-associated outer membrane proteins (OMPs) in outer membrane complexes (OMC). The virulence-associated 92, 32 and 30 kDa OMPs were purified and the N-terminal amino acid sequences were determined. The N-terminal amino acid sequences of the 30 and 32 kDa OMPs show homology with the C-terminal fragment of the P.93 precursor of the 69 kDa OMP (pertactin). The purified 32 kDa OMP was protective in the i.c. test when presented as mixed protein-detergent micelles. The 92 kDa OMP became a protective antigen when nonprotective levels of pertussis toxin were added. We found a correlation between the i.c. mouse protection value and the 92 kDal38 kDa (porin) ratio in OMC preparations.

Previous studies indicated a reproducible pattern of altered glycosphingolipid biosynthesis accompanying late stages of liver tumorigenesis in the rat induced by the carcinogen 2-acetylaminofluorene. The sequence began with a dramatic elevation in CMP-sialic acid:lactosylceramide sialyltransferase and was followed by sequential elevations and eventual depressions in other enzymes catalyzing sugar transfers to glycolipid acceptors. The present study focused on the early events of glycolipid biosynthesis during the first 11 weeks of 2-acetylaminofluorene administration according to the same feeding schedule as used previously. Transient elevations in CMP-sialic acid synthetase and elevations in neutral glycosphingolipid precursors to gangliosides were found to precede the major elevations in CMP-sialic acid:lactosylceramide sialyltransferase (GM3 synthetase) noted earlier. Two cycles of response were observed prior to the initiation of the sustained enhancement of biosynthesis of precursor ganglioside, GM3, and/or a significant increase in total or lipid-soluble sialic acid. In vitro rates of sialyl transfer from CMP-sialic acid to endogenous protein acceptors were not altered. The results suggest that the previous observations of altered ganglioside biosynthesis following 2-acetylaminofluorene administration are not an isolated occurrence but may represent late events in a sequence or 'cascade' of biochemical change involving, as well, biosynthesis of ganglioside precursors, CMP-sialic acid and neutral glycosphingolipids.

Binding of fibronectins to gangliosides was tested directly using several different in vitro models. Using an enzyme-linked immunoabsorbent assay (ELISA), gangliosides were immobilized on polystyrene tubes and relative binding of fibronectin was estimated by alkaline phosphatase activity of conjugated second antibody. Above a critical ganglioside concentration, the gangliosides bound the fibronectin (GT1b congruent to GD1b congruent to GD1a greater than GM1 much greater than GM2 congruent to GD3 congruent to GM3) in approximately the same order of efficiency as they competed for the cellular sites of fibronectin binding in cell attachment assays (Kleinman et al., Proc natl acad sci US 76 (1979) 3367). Alternatively, these same gangliosides bound to immobilized fibronectin. Rat erythrocytes coated with gangliosides GM1, GD1a or GT1b bound more fibronectin than erythrocytes not supplemented with gangliosides. Using fibronectin in which lysine residues were radioiodinated, an apparent Kd for binding to mixed rat liver gangliosides of 7.8 X 10(-9) M was determined. This value compared favorably with the apparent Kd for attachment of fibronectin to isolated plasma membranes from rat liver of 3.7 X 10(-9) M for fibronectin modified on the tyrosine residue, or 6.4 X 10(-9) M for fibronectin modified on lysine residues. As shown previously by Grinnell & Minter (Biochem biophys acta 550 (1979) 92), fibronectin modified on tyrosine residues did not promote spreading and attachment of CHO cells. It did, however, bind to cells. In contrast, lysine-modified fibronectin both bound to cells and promoted cell attachment. Plasma membranes isolated from hepatic tumors in which the higher gangliosides that bind fibronectin were depleted bound 43-75% less [125I]fibronectin than did plasma membranes from control livers. The findings were consistent with binding of fibronectins to gangliosides, including the same gangliosides depleted from cell surfaces during tumorigenesis in the rat.

The enzyme-linked immunosorbent assay (ELISA) has been used for the determination of the isotype and the specificity of Bordetella pertussis serum antibodies induced by natural infection and by vaccination. In a previous study (J. Med. Microbiol., 16, 417-426 (1984)) it was shown that the presence of pertussis serum IgA antibodies could be used as an indicator of infection: IgA antibodies were not induced by vaccination nor transported from the mother to the serum of the child. In the present study ELISA was used for the determination of IgA, IgM and IgG antibodies. From the results obtained with sera from suspected pertussis cases, it was concluded that antibodies against FHA are hardly induced by infection, in contrast to anti-LPF (determined in a fetuin sandwich ELISA) and anti-LPS antibodies. In view of the lower standard deviation of the mean anti-LPF antibody titer these antibodies were studied more extensively. From a number of bacteriologically proved pertussis cases, it was shown that high levels of IgG anti-LPF antibodies were found before IgA antibodies could be detected. On the other hand, we had the impression that IgG antibodies declined more rapidly than IgA antibodies. One has, however, to take into account that IgG antibodies are transferred from mother to child. From assay of sera from infants prior to, during and two months after vaccination (ages of vaccination: 3, 4, 5 and 12 months) it was concluded that IgG anti-LPF antibodies were induced to a much lower level by DTP-polio vaccination (10 O.U. per dose) than by natural infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibronectin is a high molecular weight adhesive glycoprotein present both on the cell surface (cellular fibronectin) and circulating free in the plasma (plasma fibronectin). To investigate the cellular origins of plasma fibronectin, monoclonal antibodies prepared against purified plasma fibronectin of the rat were used in both in vivo and in vitro pulse-chase experiments comparing livers of animals of different ages. For in vitro analyses, slices were pulsed with 3H-leucine and purified fractions of endoplasmic reticulum, Golgi apparatus and plasma membrane were prepared at various times post-chase and characterized morphologically. The total protein was solubilized with NP-40, and incorporation into fibronectin was determined from PAGE analysis of immunoprecipitates. Incorporation was greatest in 5-day-old animals, representing greater than 0.3% of the total radioactivity and was least in adults animals. Label appeared in fibronectin associated with the plasma membrane within 60 min. At earlier times, labeled fibronectin appeared first in the endoplasmic reticulum (30 min) and then in the Golgi apparatus (45 min). The findings demonstrate synthesis of fibronectin by rat liver and evidence for participation of liver endomembranes in its secretion.