Glycans from Fasciola hepatica Modulate the Host Immune Response and TLR-Induced Maturation of Dendritic Cells.
Helminths express various carbohydrate-containing glycoconjugates on their surface, and they release glycan-rich excretion/secretion products that can be very important in their life cycles, infection and pathology. Recent evidence suggests that parasite glycoconjugates could play a role in the evasion of the immune response, leading to a modified Th2-polarized immune response that favors parasite survival in the host. Nevertheless, there is limited information about the nature or function of glycans produced by the trematode Fasciola hepatica, the causative agent of fasciolosis. In this paper, we investigate whether glycosylated molecules from F. hepatica participate in the modulation of host immunity. We also focus on dendritic cells, since they are an important target of immune-modulation by helminths, affecting their activity or function. Our results indicate that glycans from F. hepatica promote the production of IL-4 and IL-10, suppressing IFNγ production. During infection, this parasite is able to induce a semi-mature phenotype of DCs expressing low levels of MHCII and secrete IL-10. Furthermore, we show that parasite glycoconjugates mediate the modulation of LPS-induced maturation of DCs since their oxidation restores the capacity of LPS-treated DCs to secrete high levels of the pro-inflammatory cytokines IL-6 and IL-12/23p40 and low levels of the anti-inflammatory cytokine IL-10. Inhibition assays using carbohydrates suggest that the immune-modulation is mediated, at least in part, by the recognition of a mannose specific-CLR that signals by recruiting the phosphatase Php2. The results presented here contribute to the understanding of the role of parasite glycosylated molecules in the modulation of the host immunity and might be useful in the design of vaccines against fasciolosis.


Hepatitis C virus dysregulates glucose homeostasis by a dual mechanism involving induction of PGC1α and dephosphorylation of FoxO1.
The maintenance of glucose homeostasis is a complex process in which the insulin signalling pathway plays a major role. Disruption of insulin-regulated glucose homeostasis is frequently observed in chronic hepatitis C (CHC) infection and might potentially contribute to type 2 diabetes mellitus (T2DM) development. Presently, the mechanism that links HCV infection to insulin resistance remains unclear. Previously, we have reported that HCV protein expression in HCV transgenic mice (B6HCV) leads to an overexpression of protein phosphatase 2A (PP2A) through an ER stress response. In the present work, we describe an association of FoxO1 hypophosphorylation and upregulation of both PGC-1α and G6Pase to phenotypic hyperglycaemia and insulin resistance in B6HCV mice. In vitro, we observed that PGC1α is concomitantly induced with PP2A. Moreover, we show that the enhanced PP2A expression is sufficient to inhibit insulin-induced FoxO1 phosphorylation via blockade of insulin-mediated Akt activation or/and through direct association and dephosphorylation of pS-FoxO1. Consequently, we found that the gluconeogenic gene glucose-6-phosphatase is upregulated. These observations were confirmed in liver biopsies obtained from CHC patients. In summary, our results show that HCV-mediated upregulation of PP2A catalytic subunit alters signalling pathways that control hepatic glucose homeostasis by inhibiting Akt and dephosphorylation of FoxO1.


Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2 study.
We recently published the results of the Steno-2 study, which evaluated the benefits of intensified integrated behavior modification and targeted polypharmacy. The results provide abundant evidence that an ambitious treatment strategy is superior to a conventional one. The study involved 160 high-risk type 2 diabetic patients with microalbuminuria-a strong risk factor of both macrovascular and microvascular complications-aged 55.1 years, who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years. In the intensive group, a stepwise treatment plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors. The conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals. The specific significant group differences in the degree of change in key clinical and biochemical variables at the end of the study were (in the intensive group): lower systolic and diastolic blood pressures, hemoglobin A(1c) (HbA(1c)), fasting serum total and low-density lipoprotein (LDL) cholesterol, fasting serum triglycerides, and 24-hour urine albumin excretion, as well as increased carbohydrate and decreased fat intake as percentage of total energy. There was no difference in weight gain between groups during follow-up and no other major side effects were reported. The primary end point was a macrovascular outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis. The differences between groups in surrogate end points translated into the following significant group differences in final clinical end points: 44% of patients in the conventional group had a cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50%. Also, the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group. In conclusion, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy, by about half. The challenge is to ensure that this experience is widely adopted in daily practice.


[The effect of anthelmintics on the serotonin content of cestodes].
The effects of some anthelminthic agents, such as praziquantel, fenasal, albendazole, on the levels of the neurotransmitter serotonin in the tissues of Hymenolepis diminuta cestodes and Mesocestoides corti tetrathyridia were examined in vivo and in vitro. The finding showed lower serotonin levels in H.diminuta after praziquantel and albendazole and in M. corti after fenasal. It is suggested that the serotonin neurotransmitter system of helminths is involved in the mechanism of action of these agents.


Do clinical or urodynamic parameters predict artificial urinary sphincter outcome in post-radical prostatectomy incontinence?
To determine whether urodynamic or clinical parameters can predict artificial urinary sphincter (AUS) outcome in patients who were incontinent after radical prostatectomy (RP). Incontinence after RP is secondary to intrinsic sphincter deficiency, but urodynamics have been advocated before AUS placement to detect factors that could limit surgical success. We reviewed all AUSs placed for RP incontinence from January 1995 to December 2004. The preoperative clinical parameters and urodynamic parameters were correlated with surgical success using linear and logistic regression analysis, respectively. Surgical failure was defined as requiring more than one pad per day. The data from 86 patients (mean age 72 years) were analyzed. Of these 86 patients, 15 (17%) were wearing more than 1 pad per day at the last follow-up visit; 11 patients (13%) considered their operation a failure; and 20 patients (24%) had postoperative urgency. The presence of detrusor overactivity (P = 0.92), low first sensation (P = 0.52), low bladder compliance (P = 0.38), and bladder capacity less than 300 mL (P = 0.58) in patients did not predict for AUS failure compared with patients without these findings. No clinical parameters were found that demonstrated a statistical association with the number of pads per day. Older patients considered themselves less improved (P = 0.012) than did younger patients. No evidence has shown that patients who are incontinent after RP who have detrusor overactivity, a low first sensation, decreased compliance, or a low bladder capacity have worse post-AUS outcomes than other patients. Older patients tended to have decreased perceived improvement. We found no clinical or urodynamic parameter that would be a contraindication to AUS placement for post-RP incontinence.


Development of Multiplex PCR Coupled DNA Chip Technology for Assessment of Endogenous and Exogenous Allergens in GM Soybean.
Allergenicity assessment of transgenic plants and foods is important for food safety, labeling regulations, and health protection. The aim of this study was to develop an effective multi-allergen diagnostic approach for transgenic soybean assessment. For this purpose, multiplex polymerase chain reaction (PCR) coupled with DNA chip technology was employed. The study was focused on the herbicide-resistant Roundup Ready soya (RRS) using a set of certified reference materials consisting of 0, 0.1%, 0.5%, and 10% RRS. Technically, the procedure included design of PCR primers and probes; genomic DNA extraction; development of uniplex and multiplex PCR systems; DNA analysis by agarose gel electrophoresis; microarray development, hybridization, and scanning. The use of the asymmetric multiplex PCR method is shown to be very efficient for DNA hybridization with biochip probes. We demonstrate that newly developed fourplex PCR methods coupled with DNA-biochips enable simultaneous identification of three major endogenous allergens, namely, Gly m Bd 28K, Gly m Bd 30K, and lectin, as well as exogenous 5-enolppyruvyl shikimate-phosphate synthase (epsps) expressed in herbicide-resistant roundup ready GMOs. The approach developed in this study can be used for accurate, cheap, and fast testing of food allergens.


The effects of zinc on the structure and functioning of a freshwater community: A microcosm experiment.
A major problem with risk assessment of chemicals is the extrapolation of laboratory single-species toxicity tests, which oversimplify the actual field situation by ignoring species interactions, to natural communities. The authors tested if the bioavailability-normalized 5% hazardous concentration (HC5) estimated from chronic planktonic single-species toxicity data (HC5plankton ) for zinc (Zn) is protective for a plankton community and investigated the direct and indirect effects of Zn (at HC5 and HC50) on a freshwater community's structure and function. Microcosms were exposed to 3 different Zn concentrations (background, HC5plankton = 75 μg Zn/L and HC50plankton = 300 μg Zn/L) for 5 wk. The planktonic groups revealed a consistent no-observed-effect concentration for the community of 75 μg Zn/L, similar to or higher than the HC5plankton , thus suggesting its protectiveness in the present study. At 300 μg Zn/L a significant reduction in cladocerans resulted in increases of rotifer, ciliate, and phytoplankton abundance. In addition, the phytoplankton community shifted in dominance from grazing-resistant to edible species. Contrary to the species sensitivity distribution (SSD) prediction, which identified phytoplankton as the most sensitive group, only the total chlorophyll and the abundance of 2 phytoplankton species were adversely affected at 300 μg Zn/L. Thus, although the HC5 estimated from the bioavailability-normalized SSD was overall protective for the plankton community, the SSD was not able to correctly predict the species sensitivity ranking within their community context at the HC50. Environ Toxicol Chem 2016;35:2698-2712. © 2016 SETAC.


Underdeveloped or underreported? Coverage of pretesting practices and recommendations for design of text message-based health behavior change interventions.
Text messaging interventions for health are becoming increasingly popular, but it is unclear how rigorously such interventions are developed and pretested before being implemented. Pretesting is important to the development of successful health communication interventions. This study reviewed the literature published on text messaging health behavior change interventions and examined pretesting practices. Results showed that pretesting is rarely mentioned in articles, although it is not clear as to why. Six articles mentioned pretesting practices conducted for their mobile intervention, and three articles were written specifically on the pretesting of an intervention. Most pretesting used qualitative methods. Recommendations are provided on pretesting best practices and pretesting reporting to help other researchers in the field of mobile health.


Masking nanoparticle surfaces for sensitive and selective colorimetric detection of proteins.
We have developed a convenient and efficient colorimetric detection system for protein targets using aptamer-gold nanoparticle conjugates. We take advantage of the correlation between the catalytic properties and the exposed surface area of the nanoparticles, which is inversely proportional to the amount of the aptamer-bound protein targets. As the concentration of the protein target increases, the nanoparticle surface area becomes more masked, thus increasing the reduction time of 4-nitrophenol for the color change. We also reduce the detection time by either redesigning the aptamer sequences or regulating their density. This detection system is highly selective, discriminating the target protein even at a concentration 1000 times higher than the limit of detection (LOD). Importantly, to the best of our knowledge, the LOD with the unaided eye in this work is the lowest for a colorimetric detection system using lysozyme as a model protein (16 nM). Lysozyme in chicken egg whites is directly analyzed using our detection system, whose results are in excellent agreement with the enzyme-linked immunosorbent assay (ELISA) analysis.


Context-based coding of bilevel images enhanced by digital straight line analysis.
A new efficient compression scheme for bilevel images containing locally straight edges is presented. This paper is especially focused on lossless (intra) coding of binary shapes for image and video objects, but other images with similar characteristics such as line drawings, layers of digital maps, or segmentation maps are also encoded efficiently. The algorithm is not targeted at document images with text, which can be coded efficiently with dictionary-based techniques as in JBIG2. The scheme is based on a local analysis of the digital straightness of the causal part of the object boundary, which is used in the context definition for arithmetic encoding. Tested on individual images of standard TV resolution binary shapes and the binary layers of a digital map, the proposed algorithm outperforms PWC, JBIG, JBIG2, and MPEG-4 CAE. On the binary shapes, the code lengths are reduced by 21%, 27%, 28%, and 41%, respectively. On the map layers, the reductions are 31%, 34%, 32%, and 64%, respectively. The algorithm is also more efficient on the test material than the state-of-the-art generic bilevel image coder free tree.


Review of threats to the Pacific seahorse Hippocampus ingens (Girard 1858) in Peru.
Illegal wildlife trade has been identified as a major source of global commerce of seahorses. The Convention on International Trade in Endangered Species of Wild Fauna and Flora listed the genus Hippocampus in Appendix II in 2004, when several countries that commercialized these species also banned transactions through domestic legislation, Peru being one of them. Nevertheless, since the 2004 ban was decreed in Peru, transactions have continued, including international commerce, as well confiscations of illegal seahorse Hippocampus ingens (Girard 1858) products. The authors reviewed three official government sources for information on seahorse trade in Peru, identifying differences in the reporting of the two agencies that monitor exports and imports of seahorses, likely due to non-standardized use of product categorization codes (Partidas Arancelarias). Confiscations reported by one of the agencies confirmed that illegal trade continued despite the ban and in similar amounts of what was exported by Peru before the ban (1053 kg confiscated in 2019 vs. 1460 kg exported in 2004, an estimated 437,888 and 607,067 seahorses, respectively). This review highlights gaps in seahorse conservation in Peru, which include research gaps (e.g., taxonomy, biology and use of habitats) as well as the identification of fisheries impact and improvements in by-catch reporting. This review also highlights areas for possible improvement in international trade (e.g., standardized descriptions of Partidas) that ultimately would allow the country to follow the Convention for Illegal Trade of Endangered Species regulations for seahorses.


Ab initio modeling of amide-stabilized, oligo(ethylene glycol)-terminated self-assemblies: in-SAM molecular geometry, orientation, and hydrogen bonding.
Under the constraint that sulfur atoms form a hexagonal (square root 3 x square root 3)R30 degrees overlayer on the (111) gold surface, the optimized geometry of periodic arrays of HS(CH2)3CONH-(CH2CH2O)3H molecules has been found ab initio, by exploiting the BP86 exchange-correlation functional with 6-31G and "general" basis sets. The obtained data suggests that several prominent features of in-SAM molecular geometry and orientation stand out from conclusions based on single-molecule modeling. In particular, changing of amide-related dihedrals is shown to dominate in adjustment of molecular constituents to the assembly environment and to result in a substantial shortening of the hydrogen bond distance between nearest-neighbor amides. First demonstrated here, the full account to the intermolecular interaction within periodic arrays of amide-bridged, oligo(ethylene glycol)-terminated alkanethiolates forms a new platform for arguable modeling of SAM apparent properties.


Acute respiratory distress syndrome in the pediatric age: an update on advanced treatment.
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks definitive treatment. The cornerstone of management is sound intensive care treatment and early anticipatory ventilation support. A mechanical ventilation strategy aiming at optimal alveolar recruitment, judicious use of positive end-respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for managing this lung disease. Several treatments have been proposed in rescue settings, but confirmation is needed from large controlled clinical trials before they be recommended for routine care. Non-invasive ventilation (NIV) is suggested with a cautious approach and a strict selection of candidates for treatment. Mild and moderate cases can be efficiently treated by NIV, but this is contra-indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO2 R), used as an integrated tool with conventional ventilation, is playing a new role in adjusting respiratory acidosis and CO2. The proposed benefits of ECCO2 R over extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial surface contact, avoidance of pump-related side effects and technical complications, as well as lower costs. The advantages and disadvantages of inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended for ARDS and acute lung injury (ALI) in children and adults because iNO results in a transient improvement in oxygenation but does not reduce mortality, and may be harmful. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS. However, studies which are still controversial have shown that surfactant supplementation can improve oxygenation and decrease mortality in pediatric and adolescent patients in specific conditions and, when applied in different modes and doses, also in neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS remains supportive, aimed at improving gas exchange and preventing complications. Progress in the treatment of ARDS must be addressed toward the new paradigm of the disease pathobiology to be applied to the disease definition and to predict the treatment outcome, also with the perspective to develop predictive and personalized medicine that highlights new and challenging opportunities in terms of benefit for patient's safety and doctor's responsibility, with further medico-legal implication.


PHAS proteins as mediators of the actions of insulin, growth factors and cAMP on protein synthesis and cell proliferation.
PHAS-I and PHAS-II are members of a newly discovered family of proteins that regulate translation initiation. PHAS-I is expressed in a wide variety of cell types, but it is highest in adipocytes, where protein synthesis is markedly increased by insulin. PHAS-II is highest in liver and kidney, where very little PHAS-I is found. PHAS proteins bind to eIF-4E, the mRNA cap-binding protein, and inhibit translation of capped mRNA in vitro and in cells. In rat adipocytes PHAS-I is phosphorylated in at least five sites, all of which conform to the consensus, (Ser/Thr)-Pro. Both PHAS proteins are phosphorylated in response to insulin or growth factors, such as EGF, PDGF and IGF-1. Phosphorylation in the appropriate site(s) promotes dissociation of PHAS/eIF-4E complexes. This allows eIF-4E to bind to eIF-4G (p220), thereby increasing the amount of the eIF-4F complex and the rate of translation initiation. Increasing cAMP promotes PHAS-I dephosphorylation and increases binding to eIF-4E. Unlike PHAS-I, PHAS-II is readily phosphorylated by PKA in vitro, suggesting that regulation of the two proteins differs. However, increasing cAMP in cells also promotes dephosphorylation of PHAS-II. Thus, PHAS proteins appear to be key mediators not only of the stimulatory effects of insulin and growth factors on protein synthesis, but also of the inhibitory effects of cAMP. Moreover, by controlling eIF-4E PHAS proteins may be involved in the control of cell proliferation, as increasing eIF-4E is mitogenic and can even cause malignant transformation of cells. MAP kinase readily phosphorylates both PHAS-I and PHAS-II in vitro, but inhibiting activation of MAP kinase does not attenuate the effects of insulin on increasing phosphorylation of the PHAS proteins in adipocytes or skeletal muscle. MAP kinase phosphorylates neither PHAS-I nor PHAS-II at a significant rate when the proteins are bound to eIF-4E. Therefore, the role of MAP kinase in promoting the dissociation of PHAS/eIF-4E complexes is not clear. Of several protein kinases tested, only casein kinase-II phosphorylated PHAS-I when it was bound eIF-4E. Indeed, the bound form of PHAS-I was phosphorylated more rapidly than the free form. However, it is unlikely that casein kinase II regulates either PHAS protein, as the major site (Ser111) in PHAS-I phosphorylated by casein kinase II in vitro is not phosphorylated in adipocytes, and PHAS-II is not a substrate for casein kinase-II. Pharmacological and genetic evidence indicates that the mTOR/p70S6K pathway is involved in the control of PHAS-I and -II. Thus, PHAS proteins may be mediators of the effects of this pathway on protein synthesis and cell proliferation.


Whole-genome classification of rotavirus C and genetic diversity of porcine strains in the USA.
Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19-G31, P[22]-P[26], R5, A9-A12, N9-N10, T7-T9 and E6-E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.


Dietary NaCl does not affect blood pressure in healthy cats.
The purpose of this study was to assess the effects of dietary salt intake on systolic blood pressure, water intake, urine output, and urine concentration in cats. Ten healthy young adult cats (mean age 2.5 years) were randomly divided into 2 groups and fed either a control diet (0.46% Na and 1.33% Cl on a dry matter [DM] basis) or a diet with a moderately increased salt content (1.02% Na and 2.02% Cl on a DM basis) for 2 weeks. After a 1-week wash-out period, each group was switched to the opposite diet for 2 weeks. During each 2-week study period, food and water intake, urine volume, urine specific gravity, and urine osmolality were measured daily. Systolic blood pressure (calculated as the mean of 5 readings measured with a Doppler flow detector) was assessed twice daily. No significant effect of diet composition was found on systolic blood pressure, and blood pressure measurements remained within reference limits throughout the study in all 10 cats. However, animals fed the higher salt diet had significantly increased water intake and urine osmolality, and significantly decreased urine specific gravity in comparison to animals fed the control diet. Examination of results of this preliminary study suggests that feeding a diet with moderately increased salt content increases water intake and causes diuresis without increasing systolic blood pressure in healthy adult young cats.


Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and NNK.
3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and 2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA, measured with the Comet assay to assess DNA damage, in a cytochrome P450-dependent manner in primary normal human lung cells in culture, but the mutagenesis of 3MI has been controversial. In the present study, the mutagenic potential of 3MI was compared to the prototypical cigarette smoke carcinogens benzo(a)pyrene (B(a)P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). 3MI, B(a)P, and NNK were incubated with the Salmonella typhimurium strain TA98, which is known to detect the most common subtype of cigarette smoke-induced mutagenicity, frameshift mutations in DNA, and with Salmonella typhimurium strain TA100, which detects base pair substitution mutants, with five sources of P450-mediated bioactivation: rat liver S9, human lung microsomes, recombinant CYP2A13, purified CYP2F3, and recombinant CYP1A1. Only B(a)P was mutagenic in TA100, and it was bioactivated by human lung microsomes and rat liver S9 sources of P450s. However, with the TA98 strain, CYP1A1, CYP2A13, CYP2F3, and human lung microsomes bioactivated 3MI to highly mutagenic intermediates, whereas neither human nor rat liver S9 subcellular fractions formed mutagenic intermediates from 3MI. Quantitative Western blot analysis verified that all three respiratory enzymes were present in human lung microsomes in widely varying amounts. These results indicate that metabolism of 3MI by human lung-expressed cytochrome P450 enzymes but not hepatic P450s elicits equivalent or higher mutagenicity than the prototype cigarette smoke mutagens B(a)P and NNK and indicates that 3MI is a likely human pulmonary carcinogen.


Isolation, mapping, and characterization of two barley multiovary mutants.
Mutations in homeotic genes disturb the spatial and temporal patterns of development, often leading to the appearance of tissues in abnormal locations. Many homeotic genes, involved in flower development, code for proteins with a highly conserved domain called the MADS box, which acts as a sequence-specific DNA binding protein. Two floral development mutants were isolated from a fast neutron irradiated M2 barley population. The phenotypes are multiovary, that is, stamens replaced with carpels, designated mo7a, and stamens replaced with carpels and lodicules converted to leaflike structures, designated mo6b. These phenotypes resemble the Arabidopsis mutants APETALA3 (AP3) and PISTILATA (PI). The mo6b and mo7a mutants were mapped to the centromeric region of chromosome 1 (7H) and to the telomeric region of chromosome 3 (3H), respectively.


Rat hepatocytes bind to synthetic galactoside surfaces via a patch of asialoglycoprotein receptors.
The binding of rat hepatocytes to flat polyacrylamide surfaces containing galactose is sugar-specific, requires Ca+2, and occurs only above a critical concentration of sugar in the substratum [Weigel et al., 1979, J. Biol. Chem., 254, 10,830). Binding is completely inhibited by asialo-orosomucoid but not by orosomucoid or asialo-agalacto-orosomucoid, suggesting that cell binding is mediated by asialoglycoprotein receptors. Asialo-orosomucoid was labeled with fluorescein isothiocyanate and used as a direct fluorescent probe to monitor the distribution of cell surface asialoglycoprotein receptors before and after hepatocyte binding to galactoside or control substrata. Cells bound at 37 degrees C were de-adhered at 4 degrees C using the Ca+2 chelator EGTA. The released cells were then stained with fluorescein-asialo-orosomucoid, fixed, washed, and examined by fluorescence microscopy. On freshly isolated cells before binding, the distribution of asialoglycoprotein receptors appears diffuse and nonclustered. However, more than half of the cells released intact from a galactoside surface had a single large (4 micrometer2) fluorescent patch. The receptor patch cannot be detected on cells while they are bound to a galactoside surface but rather only on released cells, indicating that the cell-substratum junction is the site of the receptor patch. No asialoglycoprotein receptor patches (less than or equal to 1%) were observed on cells that were incubated on, but did not bind to, an underivatized polyacrylamide surface or to a surface with a galactose concentration below the critical concentration for binding. Furthermore, no receptor patches were present on cells that had bound to and were subsequently released from substrata that did not contain galactose, including glass, tissue culture plastic, nontissue culture plastic, and collagen. The distribution of asialoglycoprotein receptors is preserved at 4 degrees C because at 37 degrees C the patches disappear with a half-life of approximately 2.6 min. The results directly demonstrate that a large cluster of asialoglycoprotein receptors mediates the binding of rat hepatocytes to a galactoside surface.


Fondaparinux or enoxaparin: a comparative study of postoperative bleeding in coronary artery bypass grafting surgery.
Preoperative treatment with anti-coagulants for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) exposes patients undergoing surgical revascularization to a higher risk of perioperative bleeding. The aim of this study was to compare the effect on bleeding and transfusion needs during cardiac surgery for patients treated with enoxaparin or fondaparinux. Using a combined retrospective and prospective approach, we studied the outcome of 147 patients with NSTE-ACS referred to coronary artery bypass grafting in terms of bleeding, blood transfusions and other complications. Eighty patients were treated preoperatively with enoxaparin, and 67 patients with fondaparinux. There was no significant difference in postoperative bleeding (532 +/- 355 for enoxaparin group vs. 580 +/- 300 ml for fondaparinux group, p = ns) or transfusion needs for the two groups. A subgroup analysis of the fondaparinux group showed a significantly higher amount of postoperative bleeding after 12 h for patients when preoperative treatment with fondaparinux was discontinued less than 36 h prior to surgery compared to more than 36 h. This study suggests that preoperative treatment with fondaparinux for NSTE-ACS is as safe as enoxaparin in terms of postoperative bleeding and transfusion needs. Findings support discontinuation of fondaparinux at 36 h prior to surgery.


Chemical profile of persian lime seeds (Citrus Limettioides T.): Focus on limonoids and polyphenols.
Citrus fruit industrial processing generates tons of waste composed of peels, seeds and pulp. Incorrect disposal of these residues may harm the environment. The extraction of oil and bioactive compounds from citrus fruit seeds may be considered a sustainable alternative to the disposal of waste by the citrus agroindustry. In order to provide safe disposal of citrus waste an evaluation of its composition is necessary. Here we report the results of the application of a methodology to evaluate the composition the seeds of Citrus limettioides. In the first step, extraction with supercritical carbon dioxide was used. This work allowed the isolation and identification of four aglycone-type limonoids by High Performance Liquid Chromatography and Nuclear Magnetic Resonance, identified as limonin, nomilin, deacetylnomilin, and obacunone. In addition, six other polar limonoids and two glycosyl flavonoids were identified by HPLC-ESI/MS/MS.


Efficacy of a canarypox virus-vectored vaccine against feline leukaemia.
Canarypox virus recombinant vaccines have a unique efficacy and safety profile for the vaccinated host because the canarypox virus is non-replicative in mammalian hosts. After the vaccination of a mammalian species, recombinant canarypox viruses express the inserted genes but cannot multiply in the host. They stimulate a strong immune response in the absence of any virus amplification in the host or any viral spread into the environment. A new canarypox-based recombinant vaccine is the canarypox-feline leukaemia virus (FeLV) vaccine (EURIFEL FeLV; Merial) that expresses the FeLV env and gag protective genes. This paper describes experiments which demonstrate that it is effective against any oronasal FeLV challenge. The protection was shown to be solid against an oronasal challenge one year after the initial vaccination, and was effective against a very severe 'in-contact' challenge. Furthermore, the canarypox virus-FeLV vaccine was effective without an adjuvant.


Associations between Symptoms and Exercise Barriers in Breast Cancer Survivors.
Despite exercise benefits for cancer survivor health, most breast cancer survivors do not meet exercise recommendations. Few studies have examined associations between psychosocial symptoms and exercise barriers in this population. To improve physician exercise counseling by identifying survivors with high barriers in a clinical setting, associations between breast cancer symptoms (fatigue, mood, sleep quality) and exercise barriers were investigated. Physically inactive survivors (N = 320; average age 55 ± 8 years, 81% White, 77% cancer stage I or II) completed a baseline survey for a randomized physical activity trial and secondary analyses were performed. Potential covariates, exercise barriers interference score, Fatigue Symptom Inventory, Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index were assessed. Based on multiple linear regression analyses, only HADS Global (B = 0.463, p < 0.001) and number of comorbidities (B = 0.992, p = 0.01) were independently associated with total exercise barriers interference score, explaining 8.8% of the variance (R2 = 0.088, F(2,317) = 15.286, p < 0.001). The most frequent barriers to exercise for survivors above the HADS clinically important cut point included procrastination, routine, and self-discipline. These results indicate greater anxiety levels, depression levels, and comorbidities may be independently associated with specific exercise barriers. Health professionals should consider mood and comorbidities when evaluating survivors for exercise barriers, and tailoring exercise counseling.


Decoupling function and anatomy in atlases of functional connectivity patterns: language mapping in tumor patients.
In this paper we construct an atlas that summarizes functional connectivity characteristics of a cognitive process from a population of individuals. The atlas encodes functional connectivity structure in a low-dimensional embedding space that is derived from a diffusion process on a graph that represents correlations of fMRI time courses. The functional atlas is decoupled from the anatomical space, and thus can represent functional networks with variable spatial distribution in a population. In practice the atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects. The method also successfully maps functional networks from a healthy population used as a training set to individuals whose language networks are affected by tumors.


Treatment options and recommendations to reduce preterm births in women with short cervix.
Premature shortening of the cervix, or short cervix, is the most predictive risk factor for preterm birth. Results of clinical studies of interventions to prevent preterm birth have shown that identifying at-risk women on the basis of cervical length versus obstetric history alone improves the likelihood of timely interventions with cervical cerclage or progesterone supplementation, improving outcomes. Debate continues over the use of cerclage; however, results of a meta-analysis of randomized controlled trials provide evidence to support its use in women who have history of prior preterm birth and who develop short cervix before 24 weeks' gestation. Results of the recent PREGNANT trial, consistent with the earlier Fetal Medicine Foundation study, support the use of vaginal progesterone for prevention of preterm birth. In women identified by transvaginal ultrasound to have short cervix (10-20 mm) in midtrimester, daily vaginal progesterone gel reduced the risk of preterm birth before 33 weeks' gestation by 45% and before 28 weeks' gestation by 50%. Occurrence of any morbidity and mortality event also was significantly reduced by 43%, with a 61% reduction in the rate of respiratory distress syndrome in infants born to women receiving vaginal progesterone gel versus those receiving placebo. The safety profile of progesterone treatment in early pregnancy is well established, and studies of vaginal progesterone for prevention of preterm birth have identified no additional safety issues. Adverse events were comparable between women receiving progesterone and those receiving placebo. Recent guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend vaginal progesterone in women with no prior spontaneous preterm birth and cervical length of 20 mm or less at 24 weeks' gestation or earlier. Future studies will refine strategies for prevention of preterm birth to address other risk factors and determine the role of other interventions.


[Metastatic potential: a generic characteristic of the primary tumor].
How do metastases arise from the primary tumor? To address this important question at both cognitive and clinical levels, the somatic genetic of cancers has proposed two models based on our knowledge of genes underlying tumor progression through the use of both patients' tumors and experimental models. The first model proposes the emergence of a subpopulation of rare and variant highly metastatic cells. The second model suggests the occurrence of a pre-malignant state of all the tumor cells which further metastasize without additional transitions in gene expression. Today, the science of functional genomic allows revisiting this debatted concern.


[Examination of Prognosis and Adjuvant Chemotherapy in Stage Ⅱ and Stage Ⅲ Resected Colorectal Cancer in the 9th Edition Japanese Classification of Colorectal Carcinoma].
In the 9th edition Japanese Classification of Colorectal Carcinoma, Stage Ⅱ and Stage Ⅲ colorectal cancer(CRC)were subdivided by TNM classification on invasion and number of lymph node metastases. We studied prognostic comparison and relation of adjuvant chemotherapy at the new classification. We included 400 cases with resected Ⅱ and Ⅲ CRC from 2007 to 2014. Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc were 97/68/20/24/124/67 cases. Adjuvant chemotherapy was performed at 19/32/45/66/59/70% in Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc, with or without adjuvant chemotherapy at each stage survival rates were compared. In Ⅱa/Ⅱb/Ⅱc, DSS was 97/97/82% and DFS was 89/88/76%, and the prognosis of Ⅱc was significantly worse. In Ⅲa/Ⅲb/Ⅲc, DSS was 95/86/57% and DFS was 82/77/41%. By the presence or absence of adjuvant chemotherapy, significantly differences were obtained at Ⅲb and Ⅲc. Prognosis of Ⅱc was almost same as Ⅲb, and prognosis of Ⅲa was almost same as Ⅱb. Therefore, we considered adjuvant chemotherapy with oxaliplatin should be performed to Ⅱc, Ⅲb, and Ⅲc.


The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion.
Although many proteins can misfold into a self-seeding amyloid-like conformation, only six are known to be infectious, that is prions. The prions [PSI(+)], [PIN(+)], [URE3], [SWI(+)] and [HET-s] cause distinct heritable physiological changes in fungi, whereas PrP(Sc) causes infectious encephalopathies in mammals. It is unknown whether 'protein-only' inheritance is limited to these exceptional cases or whether it represents a widespread mechanism of epigenetic control. Towards this goal, we now describe a new prion formed by the Cyc8 (Ssn6) protein of Saccharomyces cerevisiae. Analogously to other yeast prions, transient overproduction of a glutamine-rich region of Cyc8 induced a heritable dominant cyc8(-) phenotype that is transmitted cytoplasmically and is dependent on the chaperone Hsp104 and the continued presence of the Cyc8 protein. The evolutionarily conserved Cyc8-Tup1 global transcriptional repressor complex forms one of the largest gene regulatory circuits, controlling the expression of more than 7% of yeast genes. Our finding that Cyc8 can propagate as a prion, together with a recent report that Swi1 of the Swi-Snf global transcriptional regulatory complex also has a prion form, shows that prionization can lead to mass activation or repression of yeast genes and is suggestive of a link between the epigenetic phenomena of chromatin remodelling and prion formation.


Partitioning visual displays aids task-directed visual search.
We reduced time to detect target symbols in mock radar screens by adding perceptual boundaries that partitioned displays in accordance with task instructions. Targets appeared among distractor symbols either close to or far from the display center, and participants were instructed to find the target closest to the center. Search time increased with both number of distractors and distance of target from center. However, when close and far regions were delineated by a centrally presented "range ring," the distractor effect was substantially reduced. In addition, eye movement patterns more closely resembled a task-efficient spiral when displays contained a range ring. Results suggest that the addition of perceptual boundaries to visual displays can help to guide search in accordance with task-directed constraints. Actual or potential applications of this research include the incorporation of perceptual boundaries into display designs in order to encourage task-efficient scanpaths (as identified via task analysis and/or empirical testing).


Macroevolution of floral scent chemistry across radiations of male euglossine bee-pollinated plants.
Floral volatiles play key roles as signaling agents that mediate interactions between plants and animals. Despite their importance, few studies have investigated broad patterns of volatile variation across groups of plants that share pollinators, particularly in a phylogenetic context. The "perfume flowers", Neotropical plant species exhibiting exclusive pollination by male euglossine bees in search of chemical rewards, present an intriguing system to investigate these patterns due to the unique function of their chemical phenotypes as both signaling agents and rewards. We leverage recently-developed phylogenies and knowledge of biosynthesis along with decades of chemical ecology research to characterize axes of variation in the chemistry of perfume flowers, as well as understand their evolution at finer taxonomic scales. We detect pervasive chemical convergence, with many species across families exhibiting similar volatile phenotypes. Scent profiles of most species are dominated by compounds of either the phenylpropanoid or terpenoid biosynthesis pathways, while terpenoid compounds drive more subtle axes of variation. We find recapitulation of these patterns within two independent radiations of perfume flower orchids, in which we further detect evidence for rapid evolution of divergent floral chemistries, consistent with the putative importance of scent in the process of adaptation and speciation.


[The expression patterns of genes in different biotypes by genome addition].
The patterns of SOD, EST and haemoglobin genes expression among the different combinations conducted with genome addition were investigated. The erythrocyte expression of these isozymes and protein were visualized by histochemical staining after polyacrylamide gradient gel electrophoresis. The results of our electrophoresis analysis have revealed that biochemical polymorphism exists in the combinations, and these genetic variance have resulted from the contribution of different genomes. This study provides additional evidence that gene dosages can be interpreted from the enzyme patterns and electrophoretic staining intensities existed in different ploidies, which suggests that subunit interactions for SOD are co-operative and additive. This would indicate that each allele could be differentially regulated so that even one-third genome can be expressed in triploid individuals. These genetic data could be used to construct genome specific varieties, and would not only help to maximize efficiency in the use of different biotypes identification, but also help to maximize studying the relationship between gene dosage, expression and regulation.


Electrophysiological assessment of language function following stroke.
Event-related brain potentials (ERPs) were used to assess language function after stroke and demonstrate that it is possible to adapt neuropsychological tests to evaluate neurocognitive function using ERPs. Prior ERP assessment work has focused on language in both healthy individuals and case studies of aphasic neurotrauma patients. The objective of the current study was to evaluate left-hemisphere stroke patients who had varying degrees of receptive language impairment. It was hypothesized that ERPs would assess receptive language function accurately and correlate highly with the neuropsychological data. Data were collected from 10 left-hemisphere stroke patients; all were undergoing rehabilitation at the time of testing. Each patient received a battery of neuropsychological tests including the Peabody Picture Vocabulary Test-Revised (PPVT-R; Minnesota: American Guidance Service, 1981). ERPs were recorded during a computerized PPVT-R, in which pictures are presented followed by digitized spoken words that are either congruent or incongruent with the pictures. Incongruent spoken words within an individual's vocabulary level elicited well-known ERP components. One of the components (the N400) could be utilized as a marker of intact semantic processing. The ERP results were subsequently quantified and N400 derivative scores correlated highly with the neuropsychological findings. The results provided a clear demonstration of the efficacy of ERP-based assessment in a neurological patient group. Language function in stroke patients can be evaluated, independent of behavior, using electrophysiological measures that correlate highly with traditional neuropsychological test scores.


Performance of sulfur dioxide passive monitors.
The following four commercial sulfur dioxide passive monitors were tested for performance and realiability: DuPont Pro-Tek C-20 air monitoring badges; MSA Vaporgard Dosimeter tubes; REAL BioBadges; and 3M Sulfur Dioxide Nutshell monitors. The experiments conducted were designed to test factors critical to the operation of passive samplers: accuracy and precision; capacity; stability; analytical recovery; and the effects of exposure time, concentration, humidity, face velocity, orientation, chemical interference, and temperature. The DuPont Pro-Tek badges performed satisfactorily for all the factors tested, and the REAL BioBadges performed satisfactorily except for the instability of the SO2/tetrachloromercurate complex when stored. An alternate monitoring system, REAL BioBadges containing deionized water absorbent had a limited capacity. Only the MSA dosimeters exhibited unsatisfactory performance. The 3M Nutshell monitor was withdrawn by the manufacturer after only partial evaluation.


Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development.
Overactive bladder (OAB) is a pervasive clinical problem involving alterations in both neurogenic and myogenic activity. While there has been some progress in understanding neurogenic inputs to OAB, the mechanisms controlling myogenic bladder activity are unclear. We report the involvement of myocardin (MYOCD) and microRNA-1 (miR-1) in the regulation of connexin 43 (GJA1), a major gap junction in bladder smooth muscle, and the collective role of these molecules during post-natal bladder development. Wild-type (WT) mouse bladders showed normal development from early post-natal to adult including increases in bladder capacity and maintenance of normal sensitivity to cholinergic agents concurrent with down-regulation of MYOCD and several smooth muscle cell (SMC) contractile genes. Myocardin heterozygous-knockout mice exhibited reduced expression of Myocd mRNA and several SMC contractile genes concurrent with bladder SMC hypersensitivity that was mediated by gap junctions. In both cultured rat bladder SMC and in vivo bladders, MYOCD down-regulated GJA1 expression through miR-1 up-regulation. Interestingly, adult myocardin heterozygous-knockout mice showed normal increases in bladder and body weight but lower bladder capacity compared to WT mice. These results suggest that MYOCD down-regulates GJA1 expression via miR-1 up-regulation, thereby contributing to maintenance of normal sensitivity and development of bladder capacity.


Evaluation of left ventricular mechanical restitution in closed-chest dogs based on single-beat elastance.
The mechanical restitution of the left ventricle of closed-chest dogs was modeled as a monoexponential relation, using peak single-beat elastance as a measure of contractile strength. Data were obtained from nine dogs chronically instrumented with three sets of piezoelectric diameter gauges to assess ventricular volume and high-fidelity manometers to measure pressure. Mechanical restitution curves were obtained during both atrial and ventricular pacing in six dogs. The time constant of mechanical restitution was 64.3 +/- 11.4 msec for atrial and 122.2 +/- 26.3 msec for ventricular paced runs (p less than 0.01). These values are smaller than those previously reported from isolated hearts or isolated muscle segments. Although the time of onset of mechanical restitution was longer for atrial than for ventricular runs (255.1 +/- 14.3 versus 225.1 +/- 9.6 msec, p less than 0.05), the plateau to which mechanical function rose was not different. During ventricular pacing, fusion beats were noted in four dogs. The magnitude of the mechanical contribution of these fusion beats fell to a nadir at approximately 250 msec, suggesting that intracellular calcium available for crossbridge interaction is dropping during this time. In three additional dogs, the time constant of postextrasystolic restitution was found to vary depending on the preceding extrasystolic interval. Thus, mechanical restitution of the ventricle is a dynamic process that can be assessed using an elastance-based approach in the in situ heart.


Hypnosis, rumination, and depression: catalyzing attention and mindfulness-based treatments.
Over the past 30 years, mental health practitioners, encouraged by rigorous empirical studies and literature and meta-analytic reviews, have increasingly appreciated the ability of hypnosis to modulate attention, imagination, and motivation in the service of therapeutic goals. This article describes how hypnosis can be used as an adjunctive procedure in the treatment of depression and rumination symptoms, in particular. The focus is on attention-based treatments that include rumination-focused cognitive behavioral therapy, cognitive control training, and mindfulness-based cognitive therapy. The authors provide numerous examples of techniques and approaches that can potentially enhance treatment gains, including a hypnotic induction to facilitate mindfulness and to motivate mindfulness practice. Although hypnosis appears to be a promising catalyst of attention and mindfulness, research is required to document the incremental value of adding hypnosis to the treatments reviewed.


Anatomic study of the otic ganglion in humans.
The presentation in the literature of the anatomy of the human otic ganglion (OG) has not varied much over the past three quarters of a century. Precise, similar descriptions of its size, color, shape, and relation with neighboring structures are portrayed in numerous textbooks and articles. We have carried out a study of the OG in 30 infratemporal fossae of 15 cadavers. Otic ganglia resembling the classic description were found in less than 60% of the cases. In 13%, some thickening could be seen adjacent to the mandibular nerve and in 27%, no definite structure could be observed. Except for a fleeting mention of this occurrence in a textbook from 1927, substantiated by personal communication with an authority in the field, we could find no record of the possible absence of this structure in the available literature. We describe our findings and stress the apparent anatomic variability of the OG. The pertinent literature is reviewed.


Evaluation of food additives as alternative or complementary chemicals to conventional fungicides for the control of major postharvest diseases of stone fruit.
To evaluate potential alternatives to conventional fungicides to control decay, more than 20 food additives and generally regarded as safe compounds were tested at three concentrations in in vivo primary screenings with several cultivars of California peaches, nectarines, and plums that had been artificially inoculated with seven major postharvest pathogens: Monilinia fructicola, Botrytis cinerea, Geotrichum candidum, Alternaria alternata, Penicillium expansum, Mucor piriformis, and Rhizopus stolonifer. Overall, the best compounds were 200 mM potassium sorbate (PS), 200 mM sodium benzoate (SB), 200 mM sodium sorbate, 100 mM 2-deoxy-D-glucose, 400 mM sodium carbonate, and 250 mM potassium carbonate. Sodium and ammonium molybdates, acid lactic, and hydrogen peroxide were somewhat effective but were phytotoxic to fruit skin tissues. However, the best compounds lacked effectiveness and persistence when tested against brown rot in small-scale trials of 60-s dips in aqueous solutions at ambient temperatures; PS and SB reduced brown rot incidence by less than 40%. Rinsing treated fruit with tap water reduced the efficacy of the compounds by up to 30%. In contrast, heating the solutions to 55 or 60 degrees C significantly increased treatment efficacy. Brown rot incidence and severity were reduced by 35 and 25%, respectively, on PS-treated peaches after 7 days of incubation at 20 degrees C. However, treatment efficacy was not superior to that with water alone at these temperatures. In semicommercial trials, mixtures of fludioxonil with PS, SB, or 2-deoxy-D-glucose applied as fruit coatings on a packing line were not synergistic in their effect on brown rot, gray mold, and sour rot.


The MASTL-ENSA-PP2A/B55 axis modulates cisplatin resistance in oral squamous cell carcinoma.
Platinum-based chemotherapy is the standard first-line treatment for oral squamous cell carcinoma (OSCC) that is inoperable, recurrent, or metastatic. Platinum sensitivity is a major determinant of patient survival in advanced OSCC. Here, we investigated the involvement of MASTL, a cell cycle kinase that mediates ENSA/ARPP19 phosphorylation and PP2A/B55 inhibition, in OSCC therapy. Interestingly, upregulation of MASTL and ENSA/ARPP19, and downregulation of PP2A/B55, were common in OSCC. MASTL expression was in association with poor patient survival. In established OSCC cell lines, upregulation of MASTL and ENSA, and downregulation of B55 genes, correlated with cisplatin resistance. We further confirmed that stable expression of MASTL in OSCC cells promoted cell survival and proliferation under cisplatin treatment, in an ENSA-dependent manner. Conversely, deletion of MASTL or ENSA, or overexpression of B55α, sensitized cisplatin response, consistent with increased DNA damage accumulation, signaling, and caspase activation. Moreover, GKI-1, the first-in-class small molecule inhibitor of MASTL kinase, phenocopied MASTL depletion in enhancing the outcome of cisplatin treatment in OSCC cells, at a dose substantially lower than that needed to disrupt mitotic entry. Finally, GKI-1 exhibited promising efficacy in a mouse tumor xenograft model, in conjunction with cisplatin therapy.


Propionic acidemia revisited: a workshop report.
Propionic acidemia (PA) is one of the most frequent organic acidurias, but information on the outcome of individuals with PA is rather limited. We present data of 49 patients with PA, which were gathered from 18 metabolic centers throughout Central Europe on the occasion of an international workshop. All patients were identified by selective metabolic screening, and 86% of them were classified as having early-onset PA owing to their presentation with clinical symptoms within the first 90 days of life. Mortality rate was one third, and details of symptoms and treatment of the surviving patients are discussed. The great variation of phenotypic expression of the disease and different therapeutic strategies (especially in regard to the degree of protein restriction) used at the various institutions involved in this study imply the need for a registry of PA patients and for a multicenter prospective treatment study.


Precise detection of two-dimensional displacement based on nonlinear lateral photovoltaic effect.
Although the lateral photovoltaic effect (LPE) can be used to detect very small displacement owing to its linear characteristic of the lateral photovoltage (LPV) response to laser position, the effective measurement is limited only within the one-dimensional (1D) region between two contacts. In this work, we report a way to detect two-dimensional (2D) displacement based on a nonlinear LPE in a metal-semiconductor (MS) structure. In addition, compared with the conventional 1D method, this 2D detection possesses a much higher precision owing to its independence of LPV sensitivity of the structure, indicating it as a candidate for the new type of MS-based 2D photoelectric devices.


Applicability of an abbreviated version of the Child-OIDP inventory among primary schoolchildren in Tanzania.
There is a need for studies evaluating oral health related quality of life (OHRQoL) of children in developing countries. to assess the psychometric properties, prevalence and perceived causes of the child version of oral impact on daily performance inventory (Child-OIDP) among school children in two socio-demographically different districts of Tanzania. Socio-behavioral and clinical correlates of children's OHRQoL were also investigated. One thousand six hundred and one children (mean age 13 yr, 60.5% girls) attending 16 (urban and rural) primary schools in Kinondoni and Temeke districts completed a survey instrument in face to face interviews and participated in a full mouth clinical examination. The survey instrument was designed to measure a Kiswahili translated and culturally adapted Child-OIDP frequency score, global oral health indicators and socio-demographic factors. The Kiswahili version of the Child-OIDP inventory preserved the overall concept of the original English version and revealed good reliability in terms of Cronbach's alpha coefficient of 0.77 (Kinondoni: 0.62, Temeke: 0.76). Weighted Kappa scores from a test-retest were 1.0 and 0.8 in Kinondoni and Temeke, respectively. Validity was supported in that the OIDP scores varied systematically and in the expected direction with self-reported oral health measures and socio-behavioral indicators. Confirmatory factor analyses, CFA, confirmed three dimensions identified initially by Principle Component Analysis within the OIDP item pool. A total of 28.6% of the participants had at least one oral impact. The area specific rates for Kinondoni and Temeke were 18.5% and 45.5%. The most frequently reported impacts were problems eating and cleaning teeth, and the most frequently reported cause of impacts were toothache, ulcer in mouth and position of teeth. This study showed that the Kiswahili version of the Child-OIDP was applicable for use among schoolchildren in Tanzania.


How is dispersal integrated in life histories: a quantitative analysis using butterflies.
As dispersal plays a key role in gene flow among populations, its evolutionary dynamics under environmental changes is particularly important. The inter-dependency of dispersal with other life history traits may constrain dispersal evolution, and lead to the indirect selection of other traits as a by-product of this inter-dependency. Identifying the dispersal's relationships to other life-history traits will help to better understand the evolutionary dynamics of dispersal, and the consequences for species persistence and ecosystem functioning under global changes. Dispersal may be linked to other life-history traits as their respective evolutionary dynamics may be inter-dependent, or, because they are mechanistically related to each other. We identify traits that are predicted to co-vary with dispersal, and investigated the correlations that may constrain dispersal using published information on butterflies. Our quantitative analysis revealed that (1) dispersal directly correlated with demographic traits, mostly fecundity, whereas phylogenetic relationships among species had a negligible influence on this pattern, (2) gene flow and individual movements are correlated with ecological specialisation and body size, respectively and (3) routine movements only affected short-distance dispersal. Together, these results provide important insights into evolutionary dynamics under global environmental changes, and are directly applicable to biodiversity conservation.


Multifunctional Scaffolds with Improved Antimicrobial Properties and Osteogenicity Based on Piezoelectric Electrospun Fibers Decorated with Bioactive Composite Microcapsules.
The incorporation of bioactive compounds onto polymer fibrous scaffolds with further control of drug release kinetics is essential to improve the functionality of scaffolds for personalized drug therapy and regenerative medicine. In this study, polymer and hybrid microcapsules were prepared and used as drug carriers, which are further deposited onto polymer microfiber scaffolds [polycaprolactone (PCL), poly(3-hydroxybutyrate) (PHB), and PHB doping with the conductive polyaniline (PANi) of 2 wt % (PHB-PANi)]. The number of immobilized microcapsules decreased with increase in their ζ-potential due to electrostatic repulsion with the negatively charged fiber surface, depending on the polymer used for the scaffold's fabrication. Additionally, the immobilization of the capsules in dynamic mechanical conditions at a frequency of 10 Hz resulted in an increase in the number of the capsules on the fibers with increase in the scaffold piezoelectric response in the order PCL < PHB < PHB-PANi, depending on the chemical composition of the capsules. The immobilization of microcapsules loaded with different bioactive molecules onto the scaffold surface enabled multimodal triggering by physical (ultrasound, laser radiation) and biological (enzymatic treatment) stimuli, providing controllable release of the cargo from scaffolds. Importantly, the microcapsules immobilized onto the surface of the scaffolds did not influence the cell growth, viability, and cell proliferation on the scaffolds. Moreover, the attachment of human mesenchymal stem cells (hMSCs) on the scaffolds revealed that the PHB and PHB-PANi scaffolds promoted adhesion of hMSCs compared to that of the PCL scaffolds. Two bioactive compounds, antibiotic ceftriaxone sodium (CS) and osteogenic factor dexamethasone (DEXA), were chosen to load the microcapsules and demonstrate the antimicrobial properties and osteogenesis of the scaffolds. The modified scaffolds had prolonged release of CS or DEXA, which provided an improved antimicrobial effect, as well as enhanced osteogenic differentiation and mineralization of the scaffolds modified with capsules compared to that of individual scaffolds soaked in CS solution or incubated in an osteogenic medium. Thus, the immobilization of microcapsules provides a simple, convenient way to incorporate bioactive compounds onto polymer scaffolds, which makes these multimodal materials suitable for personalized drug therapy and bone tissue engineering.


Analysis of exhausts emitted by i.c. engines and stationary burners, by means of u.v. extinction and fluorescence spectroscopy.
Optical investigations of the exhausts emitted by internal combustion (i.c.) engines and a stationary burner were performed, in order to assess their relative role as sources of organic matter to the atmosphere. Extinction spectra of air-diluted exhausts in the 200-400 nm u.v. band reveal the expected existence of gaseous trace-species (NO, NO2 and SO2) and carbonaceous particulate matter (soot). In addition, after subtracting the absorption contribution from known species, a strong residual absorption band remains below 250 nm, which is attributed to organic aromatic matter, involving no more than two aromatic rings. A set of ex situ extinction and laser induced fluorescence (LIF) experiments were carried out on condensed combustion-water samples. Extinction measurements from the water samples show absorption spectra similar to those observed from air-diluted samples, which are attributed to low volatility organic compounds, as they are trapped in the condensed phase. Combining the indications of extinction data for both air-diluted and condensed samples, it is suggested that the absorbing species might be molecular clusters of one/two aromatic rings. LIF spectra from condensed samples evidence two fluorescence bands, centered above 300 and 400 nm, respectively, whose intensities correlate with the combustion regimes. Analogous optical analysis on rain samples, collected in an urban area, showed that rain absorption and fluorescence spectra are similar to those found in condensed exhaust samples, which is consistent with the prevailing contribution of i.c. engines to the urban air pollution. The combined experimental data suggest that the absorbing and fluorescent species trapped in the condensed samples are organic (aromatic) compounds, involving mostly one two aromatic rings structural units, since they do not absorb above 250 nm. The overall molecular weight of the trapped material is likely heavy as they show low volatility.


Dimethyl sulphoxide reduction by micro-organisms.
Dimethyl sulphoxide (DMSO) was reduced to dimethyl sulphide by a wide variety of micro-organism, including prokaryotes and eukaryotes, aerobes and anaerobes. Dimethyl sulphone was not reduced by any of the organisms tested. Cell-free extracts of Escherichia coli reduced DMSO using reduced pyridine nucleotides as electron donors. Activity was greater in anaerobically grown cells than in those grown aerobically. Two other sulphoxides, methionine sulphoxide and tetramethylene sulphoxide, substantially inhibited DMSO reduction by extracts. Mutants of E. coli, which were unable to reduce biotin sulphoxide to biotin, were tested for their ability to reduce DMSO in whole cells and extracts. These mutants were in four different gene loci, bisA to bisD. DMSO reductase activity of the mutants was generally less than that of the wild-type strain, and activity depended upon the gene locus involved, the growth medium and the growth conditions. Only the bisA mutant had very low activity under all conditions. All of the bis mutants were able to grow using methionine sulphoxide as a sulphur source, indicating that biotin sulphoxide and methionine sulphoxide are reduced by different enzyme systems. DMSO may be reduced by both of these enzyme systems.


Defining and Measuring Students' Interest in Biology: An Analysis of the Biology Education Literature.
Understanding how students develop biology interests and the roles interest plays in biology contexts could help instructors and researchers to increase science, technology, engineering, and mathematics students' motivation and persistence. However, it is currently unclear how interest has been defined or measured in the biology education research literature. We analyzed this body of literature to determine how interest has been defined and used by the biology education research community. Specifically, we determined the extent to which previously published work drew on theories that conceptualize interest. Further, we identified studies that measured student interest in biology and characterized the types of measures used. Our findings indicate that biology education researchers typically describe interest as a relationship involving positive feelings between an individual and a physical object, activity, or topic of focus. We also found that interest is often not defined, theories involving interest are not often consulted, and the most common measures of interest only assess a single aspect of the construct. On the basis of these results, we make suggestions for future research seeking to examine biology students' interest. We hope that this analysis can serve as tool for biology educators to improve their own investigations of students' interest and measure outcomes of interest-generating educational activities.


Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk.
Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date. To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk. Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity. ADIPOQ and ADIPOR1 SNP frequency among cases and controls. In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis of both studies shows an association of rs266729 with decreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99). The SNP rs266729, which tags the 5' flanking region of the ADIPOQ gene, is associated with decreased colorectal cancer risk.


Monitoring of ionized magnesium in hemodialysis patients: A useful tool to allow a personalized prescription of dialysate composition.
The dialysate magnesium (Mg) concentration is a major determinant of Mg balance in hemodialysis. This study aimed to assess the systemic variations of total (tMg) and ionized Mg (iMg) during a dialysis session using acetate or citrate fluids and 0.5 or 0.75 mM Mg. 134 patients in maintenance hemodialysis were assigned to a dialysis session with 4 different dialysates: acetate fluid with 0.5 mM Mg (1) or 0.75 mM Mg (2), citrate fluid with 0.5 mM Mg (3) or 0.75 mM Mg (4). Ionized form was measured by direct ion-selective electrode. A Mg loss was observed in both acetate (0.12 and 0.08 mmol/L) and citrate (0.13 and 0.14 mmol/L for tMg and iMg, respectively) fluid groups containing 0.5 mM Mg. The use of acetate and citrate dialysates with 0.75 mM Mg led to a significant median intra-dialytic increase of 0.15 and 0.08 mmol/L for tMg, respectively. A significant augmentation in iMg concentration with acetate (0.11 mmol/L) but not with citrate dialysate (0.02 mmol/L) was observed. While a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg. Monitoring of iMg should allow a personalized prescription in dialysate Mg.


Non-steroidal anti-inflammatory drug-induced renal failure: a brief review of the role of cyclo-oxygenase isoforms.
Non-steroidal anti-inflammatory drugs are efficacious treatments for rheumatoid arthritis and osteoarthritis. However, an adverse effect of treatment with non-steroidal anti-inflammatory drugs is acute renal failure, particularly in a subset of patients that are in a state of effective volume depletion. The frequency of this side-effect in the general treated population is not known, but is probably less than 1% per year. Non-steroidal anti-inflammatory drugs act by inhibiting the synthesis of prostaglandins, which are important mediators of renal function. In the volume-depleted state prostaglandins may counter the vasoconstriction associated with the activation of the renin-angiotensin system. Cyclooxygenase is the rate-limiting enzyme involved in the synthesis of prostaglandins. Cyclooxygenase exists in two forms: a constitutive form (cyclooxygenase-1) and an inducible form (cyclooxygenase-2), which is associated with inflammation. Non-steroidal anti-inflammatory drugs are non-specific inhibitors of both forms of cyclooxygenase. New data are emerging regarding the role of cyclooxygenase-2 in the control of renal function. In normal rat and dog kidney, cyclooxygenase-2 is sparsely expressed in the macula densa, but expression is upregulated when animals are volume depleted. This review explores the possible role of cyclooxygenase-2 in the maintenance of normal renal function in volume depleted states.


The development of a new measure of quality of life for children with congenital cardiac disease.
The purpose of the study was to develop a questionnaire measuring health-related R1 quality of life for children and adolescents with congenital heart disease, the ConQol, that would have both clinical and research applications. We describe here the process of construction of a questionnaire, the piloting and the development of a weighted scoring system, and data on the psychometric performance of the measure in a sample of 640 children and young people recruited via 6 regional centres for paediatric cardiology from across the United Kingdom. The ConQol has two versions, one designed for children aged from 8 to 11 years, and the other for young people aged from 12 to 16 years. Initial findings suggest that it is a valid and reliable instrument, is acceptable to respondents, and is simple to administer in both a research and clinical context.


ADHD: current and future therapeutics.
The stimulants, amphetamine and methylphenidate, have long been the mainstay of attention-deficit hyperactivity disorder (ADHD) therapy. They are rapidly effective and are generally the first medications selected by physicians. In the development of alternative pharmacological approaches, drug candidates have been evaluated with a wide diversity of mechanisms. All of these developments have contributed real progress in the field, but there is still much room for improvement and unmet clinical need in ADHD pharmacotherapy. The availability of a wide range of compounds with a high degree of specificity for individual monoamines (dopamine and noradrenaline) and/or different pharmacological mechanisms has refined our understanding of the essential elements for optimum pharmacological effect in managing ADHD. In this chapter, we review the pharmacology of the different classes of drug used to treat ADHD and provide a neurochemical rationale, predominantly from the use of in vivo microdialysis experiments, to explain their relative efficacy and potential to elicit side effects. In addition, we will consider how predictions based on results from animal models translate into clinical outcomes. The treatment of ADHD is also described from the perspective of the physician. Finally, the new research development for drugs to treat ADHD is discussed.


Evolved mechanisms in depression: the role and interaction of attachment and social rank in depression.
Evolved mechanisms underpinning attachment and social rank behavior may be the basis for some forms of major depression, especially those associated with chronic stress. We note the heterogeneity of depression, but suggest that some of its core symptoms, such as behavioral withdrawal, low self-esteem and anhedonia, may have evolved in order to regulate behavior and mood and convey sensitivity to threats and safety. Focusing on the evolved mental mechanisms for attachment and social rank helps to make sense of (1) depression's common early vulnerability factors (e.g., attachment disruptions, neglect and abuse), (2) the triggering events (e.g., loss of close relationships, being defeated and/or trapped in low socially rewarding or hostile environments), and (3) the psychological preoccupations of depressed people (e.g., sense of unlovableness, self as inferior and a failure). This focus offers clues as to how these two systems interact and on how to intervene.


Supporting Looked After Children and Care Leavers In Decreasing Drugs, and alcohol (SOLID): protocol for a pilot feasibility randomised controlled trial of interventions to decrease risky substance use (drugs and alcohol) and improve mental health of looked after children and care leavers aged 12-20 years.
Looked after children (LAC) and care leavers are young people who have been placed under the legal care of local authorities, in many instances due to a history of abuse and/or neglect. These young people have a significantly increased risk of substance use and mental disorder compared to their peers. The aim of the SOLID study is to assess the feasibility and acceptability of a definitive three-arm multi-centre randomised controlled trial (RCT) that compares the effectiveness of two interventions that aim to reduce risky drug and alcohol use and improve mental health among LAC aged 12 to 20 years with usual care. All LAC aged 12 to 20 years residing in four local authorities in North East England will be screened by their social worker for risky drug and alcohol use using the CRAFFT (Car, Relax, Alone, Forget, Friends and Trouble) screening tool. Those who score ≥2 will be invited to take part in the trial after further eligibility checks. Informed consent will be taken and baseline data collected. Participants will then be randomised into either (i) Motivational Enhancement Therapy, (ii) Social Behaviour and Network Therapy, or (iii) control-usual care. Follow-up data will be collected 12 months post-baseline. The baseline and follow-up questionnaires will measure self-reported drug and alcohol use, mental health and well-being and health-related quality of life. The follow-up will also collect data on placement stability and self-reported sexual, antisocial and criminal behaviour. Participants will also be asked about the use of health and social services. A detailed process evaluation, using both qualitative and quantitative methods, will be conducted and involve LAC, their carers, social workers and drug and alcohol practitioners. Despite having an increased likelihood of risky substance misuse, there is a lack of evidence outlining specific interventions to decrease drug and alcohol use targeting LAC. This feasibility study will provide the information needed to develop a definitive trial. LAC will benefit from the results of this study and the further development of the interventions. ISRCTN80786829.


Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs.
The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130-134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation.


A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.
To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea. Twenty-five patients with diarrhoea-predominant irritable bowel syndrome were randomly assigned to receive VSL#3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2-week run-in period. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily in a diary during the 10-week study, which was powered to detect a 50% change in the primary colonic transit end-point. There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre- or post-therapy. Differences in abdominal bloating scores between treatments were borderline significant (P = 0.09, analysis of covariance). Further analysis revealed that abdominal bloating was reduced (P = 0.046) with VSL#3 [mean post- minus pre-treatment score, - 13.7; 95% confidence interval (CI), - 2.5 to - 24.9], but not with placebo (P = 0.54) (mean post- minus pre-treatment score, - 1.7; 95% CI, 7.1 to - 10.4). With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency. All patients tolerated VSL#3 well. VSL#3 appears to be promising in the relief of abdominal bloating in patients with diarrhoea-predominant irritable bowel syndrome. This is unrelated to an alteration in gastrointestinal or colonic transit.


Detectable serum IgE levels in Graves' ophthalmopathy.
Graves' ophthalmopathy is an organ-specific autoimmune disorder in which the target organs are infiltrated by T lymphocytes and polymorphonuclear neutrophils that release immunoregulatory cytokines in the thyroid and retrobulbar tissues. Th2-type cytokines (IL-4, IL-5, IL-6) support the inflammatory symptoms and immunoglobulin production, e.g. IgE isotype. IgE is thought to play a part not only in allergy but also in the normal immune responses, antigen processing and presentation. Since studies report IgE accumulation around the extraocular muscles in ophthalmopathy and a correlation between the total IgE levels and the severity of ophthalmopathy in Graves' disease, we measured the total IgE levels in 56 patients with Graves' disease (associated with ophthalmopathy in 47 patients) and in 42 healthy subjects as controls to determine if IgE plays a part in the autoimmune or the local inflammatory processes. For detection we used the Enzymun-Test IgE, which was a two-step ELISA sandwich assay. Elevated circulating IgE levels could be demonstrated in non-treated hyperthyroid Graves' patients in comparison with the controls (51.02 +/- 113.16 IU/ml vs 34.95 +/- 54.91 IU/ml, P < 0.01). The IgE levels were higher in patients with active inflammatory eye signs (63.65 +/- 130.41 IU/ml) than in controls (P < 0.007). The anti-thyroid drug and glucocorticoid management decreased the total IgE levels, and the difference was significant after the treatment compared with the values at the beginning of the therapy in the Graves' patients without ophthalmopathy (17.34 +/- 6.34 IU/ml vs 13.01 +/- 9.86 IU/ml, P < 0.03). In conclusion, since the results suggested that IgE plays a role in the inflammatory eye signs in Graves' ophthalmopathy, we propose administering antihistamines for medical management.


The nursing role in ICU outreach: an international exploratory study.
It is widely acknowledged that many critically ill patients are managed outside of designated critical care units. One strategy adopted in Australia and England to assess and manage risk in these patients is the intensive care unit (ICU) outreach or liaison nurse service. This article examines how ICU outreach/liaison roles in Australia and England operate in the context of Manley's theoretical framework for advanced nursing practice. Descriptive case study design using semi-structured interviews and job descriptions as sources of evidence. Findings of interviews with six Australian ICU Liaison nurses are already published; this study replicated the Australian study with four ICU Consultant Nurses in England and mapped interview and job description data from both countries onto Manley's conceptual framework for advanced practice/consultant nurse. Four themes emerged from the English data: patient interventions, support for ward staff, liaison between ward and ICU staff and hospital-wide impact. The first three of these comprised the core service common to the roles in both countries. Manley's four subroles (expert practitioner, consultant, educator and researcher) were present across both countries. However, the interview and job description data demonstrated that there were lower expectations in Australia that the roles would lead to staff development and build capacity across the hospital system. Similarly, formal education for ward staff such as ALERT and CRiSP courses were more developed in UK. Our data demonstrate that the role undertaken in England and Australia is sufficiently comparable to use as a research intervention in international studies across the two countries. However, the macro service level differs. Job descriptions across both countries emphasized the need to influence hospital policy; however, the ICU consultant nurses in England might be considered better placed to achieve this through role title and access to the hospital executive. In both countries, the roles would benefit from systematic evaluation of the impact on outcomes. This is particularly important for longer-term integration of the role in the health services in both countries.


[Active movements of the hair cells: a new mechanism in hearing].
The concept that the outer hair cells of the cochlea possess an active motor capacity confers new dimensions on the models of the physiology and patho-physiology of the inner ear. Results are presented which suggest the existence of motor properties due to actin in the outer hair cells of the guinea pig: Permeabilized isolated outer hair cells contract in a concentration-dependent manner in the presence of ATP and calcium. Movement of the cuticular plate, but not of the stereociliary bundle, can also be observed. Contraction is inhibited by cytochalasin and by bisphosphate; The movement depends on the free calcium concentration. The calcium-binding protein calmodulin can be demonstrated in the hair cell. The substance TFP, which inactivates calmodulin, inhibits the contractile response of the hair cell; The existence of a novel infracuticular actin network can be demonstrated directly by monoclonal antibodies against actin and by selective binding of rhodamine-phalloidin to actin filaments; Furthermore, the motility of the outer hair cells is not contractile in nature, but is also associated with polymerization of actin molecules. Thus the outer hair cells are evidently capable of movement. The ATP- and calcium-induced contractions of permeabilized isolated outer hair cells suggest a physiological actin dependent mechanism. Accordingly, outer hair cells must be peripheral effector cells. The hypothetical model includes an influence of OHC motility on the micromechanics of the basilar membrane and the stereociliary region of outer hair cells to allow adaptation to high sound pressure. Moreover, control of the damping characteristics of the basilar membrane appears reasonable.


Susceptibility to Verticillium longisporum is linked to monoterpene production by TPS23/27 in Arabidopsis.
The fungus Verticillium longisporum is a soil-borne plant pathogen of increasing economic importance, and information on plant responses to it is limited. To identify the genes and components involved in the early stages of infection, transcripts in roots of V. longisporum-challenged Arabidopsis Col-0 and the susceptible NON-RACE SPECIFIC DISEASE RESISTANCE 1 (ndr1-1) mutant were compared using ATH1 gene chips. The analysis revealed altered transcript levels of several terpene biosynthesis genes, including the monoterpene synthase TPS23/27. When transgenic 35S:TPS23/27 and TPS23/27-amiRNA plants were monitored the over-expresser line showed enhanced fungal colonization whereas the silenced genotype was indistinguishable from Col-0. Transcript analysis of terpene biosynthesis genes suggested that only the TPS23/27 pathway is affected in the two transgenic genotypes. To confirm changes in monoterpene production, emitted volatiles were determined using solid-phase microextraction and gas chromatography-mass spectrometry. Levels of all identified TPS23/27 monoterpene products were significantly altered in the transgenic plants. A stimulatory effect on conidial germination and hyphal growth of V. longisporum was also seen in co-cultivation with 35S:TPS23/27 plants and upon exposure to 1,8-cineole, the main product of TPS23/27. Methyl jasmonate treatments of myc2-1 and myc2-2 mutants and analysis of TPS23/27:uidA in the myc2-2 background suggested a dependence on jasmonic acid mediated by the transcription factor MYC2. Taken together, our results show that TPS23/27-produced monoterpenes stimulate germination and subsequent invasion of V. longisporum in Arabidopsis roots.


Components of metabolic syndrome and prognosis of renal cell cancer.
This study analyzes risk associations between metabolic syndrome (MetS) components and the extent and prognosis of renal cell cancer (RCC). The independent effect of each MetS component is unclear, but they may affect RCC prognosis. The study included 13,873 RCC patients (7720 men, 6153 women) diagnosed in Finland in 1995-2012. Data on MetS components (hypertension, dyslipidemia, diabetes and obesity) were obtained as recorded diagnoses or drug purchases related to these conditions. Risk of advanced RCC at diagnosis was estimated by logistic regression. Cox proportional hazard regression was used to evaluate risk associations for RCC death by MetS components after diagnosis. Components were analyzed as time-dependent variables, and included in analyses simultaneously to evaluate their independent effects. During follow-up (median 1.92, SD 4.35 years) 5179 participants died of RCC. Risk of advanced RCC at diagnosis was associated with hypertension [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.74-90] and dyslipidemia (OR 0.52, 95% CI 0.48-0.57). After adjustment for tumor extent, hypertension remained associated with increased risk of RCC death (hazard ratio 1.44, 95% CI 1.35-1.54]. Other MetS components were not independently associated with RCC death when taking hypertension into account. Study limitations include the non-randomized design and lack of smoking status. The lower risk of advanced disease among hypertensive participants may reflect the higher proportion of incidental renal tumors found through more frequent physician contacts. Nevertheless, hypertension was independently associated with worse RCC survival, whereas other MetS components had no clear prognostic role.


Monte Carlo simulation of a lattice model for the dynamics of randomly branching double-folded ring polymers.
Supercoiled DNA, crumpled interphase chromosomes, and topologically constrained ring polymers often adopt treelike, double-folded, randomly branching configurations. Here we study an elastic lattice model for tightly double-folded ring polymers, which allows for the spontaneous creation and deletion of side branches coupled to a diffusive mass transport, which is local both in space and on the connectivity graph of the tree. We use Monte Carlo simulations to study systems falling into three different universality classes: ideal double-folded rings without excluded volume interactions, self-avoiding double-folded rings, and double-folded rings in the melt state. The observed static properties are in good agreement with exact results, simulations, and predictions of Flory theory for randomly branching polymers. For example, in the melt state rings adopt compact configurations and exhibit territorial behavior. In particular, we show that the emergent dynamics is in excellent agreement with a recent scaling theory and illustrate the qualitative differences with the familiar reptation dynamics of linear chains.


How to value safety in economic evaluations in health care? A review of applications in different sectors.
Improving (feelings of) safety is an important goal of many health systems, especially in the context of recurrent threats of pandemics, and natural disasters. Measures to improve safety should be cost-effective, raising the issue of how to value safety. This is a complex task due to the intangible nature of safety. We aim to synthesize the current empirical literature on the evaluation of safety to gain insights into current methodological practices. After a thorough literature search in two databases for papers from the fields of life sciences, social sciences, physical sciences and health sciences that empirically measure the value of increasing safety, 33 papers were found and summarized. The focus of the research was to investigate the methodologies used. Attention was also paid to theoretical papers and the methodological issues they present, and the relationship between safety and three categories of covariate results: individual characteristics, individual relationship with risk, and study design. The field of research in which the most papers were found was environmental economics, followed by transportation and health. There appeared to be two main methods for valuating safety: Contingent Valuation and Discrete Choice Experiments, within which there were also differences-for example the use of open or dichotomous choice questions. Overall this paper finds that there still appears to be a long way ahead before consensus can be attained about a standardised methodology for valuating safety. Safety valuation research would benefit from learning from previous experience and the development of more standardised methods.